Cancer is a prominent disease that poses a significant threat to human health, and the exploration of highly efficient and low-toxicity anticancer drugs remains an active area of research. Leveraging the cell-penetrating and binding capabilities of steroids, along with the multifunctional pharmacological properties of selenocyano groups, novel compounds are being designed and synthesized with the aim of discovering highly efficient and minimally toxic anti-tumor drugs. In the present study, two selenocyano pharmacophores were incorporated into estradiol to synthesize a series of estradiol diselenocyanate derivatives with a 3-selenocyanoalkoxy-17-selenocyanoester structure. The results of antiproliferative activities evaluation demonstrated that the estradiol derivatives with 3-selenocyanobutoxy moiety exhibited potent inhibitory activity against tumor cell proliferation, especially for triple negative breast cancer cell line MDA-MB-231. Their antiproliferative efficacy was significantly superior to that of estradiol analogues with 3-selenocyanooctyloxy and corresponding monoselenocyanate precursors, indicating a synergistic effect upon introduction of the second selenocyano group on cytotoxicity. The IC50 values for compound 4g against HeLa, HepG-2, and MCF-7 cells were determined as 3.20, 3.17, and 5.41 μM respectively; notably lower than those observed for its corresponding monoselenocyano precursor 3g which showed IC50 values of 15.12, 16.09, and 9.44 μM, respectively. Remarkably, the IC50 of compound 4e against MDA-MB-231 cells is only 5.04 μM and exhibited significant inhibitory activity against MDA-MB-231 zebrafish xenograft tumors. The inhibition of these compounds on tumor cell proliferation was attributed to induction of apoptosis in these cells. Thus, the estradiol diselenocyanate compounds investigated herein hold great potential as novel antitumor drugs, and warrant further investigation.

Cancer treatments often exploit oxidative stress to selectively kill tumour cells by disrupting their lipid peroxidation membranes and inhibiting antioxidant enzymes. However, lipid peroxidation plays a dual role in cancer progression, acting as both a tumour promoter and a suppressor. Balancing oxidative stress through antioxidant therapy remains a challenge, as excessive antioxidant activity may compromise the efficacy of chemotherapy and radiotherapy.

This review explores the role of antioxidants in mitigating lipid peroxidation in cancer therapy while maintaining treatment efficacy. It highlights recent advancements in nanotechnology-based targeted antioxidant delivery to optimize therapeutic outcomes.

A comprehensive literature review was conducted using reputable databases, including PubMed, Scopus, Web of Science, and ScienceDirect. The search focused on publications from the past five years (2020-2025), supplemented by relevant studies from earlier years. Keywords such as "antioxidants," "lipid peroxidation," "nanotechnology in cancer therapy," and "oxidative stress" were utilized. Relevant articles were critically analysed, and graphical illustrations were created.

Emerging evidence suggests that nanoparticles, including liposomes, polymeric nanoparticles, metal-organic frameworks, and others, can effectively encapsulate and control the release of antioxidants in tumour cells while minimizing systemic toxicity. Stimuli-responsive carriers with tumour-specific targeting mechanisms further enhance antioxidant delivery. Studies indicate that these strategies help preserve normal cells, mitigate oxidative stress-related damage, and improve treatment efficacy. However, challenges such as bioavailability, stability, and potential interactions with standard therapies remain.

Integrating nanotechnology with antioxidant-based interventions presents a promising approach for optimizing cancer therapy. Future research should focus on refining lipid peroxidation modulation strategies, assessing oxidative stress profiles during treatment, and employing biomarkers to determine optimal antioxidant dosing. A balanced approach to antioxidant use may enhance therapeutic efficacy while minimizing adverse effects.

Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential for serious adverse effects. Ototoxicity from cisplatin treatment is an important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, and vestibular dysfunction. Despite the recent approval of sodium thiosulphate for the prevention of cisplatin-induced hearing loss (CIHL) in pediatric patients, structured prevention programs are not routinely implemented in most hospitals, and reducing platinum-induced ototoxicity in adults remains an important clinical problem without established treatment options. Cochlear oxidative stress plays a fundamental role in CIHL. Here, we review the molecular mechanisms leading to oxidative stress in CIHL and the clinical and preclinical studies testing antioxidants in CIHL to guide future clinical trials in assessing the efficacy and safety of candidate antioxidant compounds in this clinical setting.

Tocopherols, potent bioactive compounds with anticancer properties, remain understudied in herbal medicinal plants, presenting a significant knowledge gap in the field of natural anticancer agents. This review evaluates tocopherol-containing plants for their anticancer potential, analyzing Scopus publications from 2016 to 2024. Fifteen herbal medicinal plants were identified as promising candidates, including Bulbine anguistifolia Poelln, Punica granatum L., Moringa oleifera, Kigelia pinnata, and Typhonium flagelliforme Lodd. The review explores tocopherols' anticancer mechanisms, including apoptosis induction and cell cycle arrest. Factors influencing tocopherols' anticancer effects are examined, such as their forms (α, β, γ, δ), concentrations, plant parts utilized, and their stability in various plants. Additionally, emerging research on semi-synthetic tocopherol derivatives is analyzed, highlighting their potential as adjuvants in chemotherapy and their role in enhancing drug delivery and reducing side effects. This comprehensive analysis aims to advance the development of plant-based anticancer pharmaceuticals and improve cancer treatment strategies. By elucidating the mechanisms and potential of tocopherol-containing plants, this review provides a foundation for future research in plant-based anticancer therapies. It emphasizes the need for further investigation into these plants' anticancer properties, potentially leading to novel, more effective, and less toxic cancer therapies. The findings presented here contribute to a nuanced understanding of how tocopherol-containing plants can be leveraged in the development of future anticancer drugs.

Natural Health Products (NHPs) have long been considered a valuable therapeutic approach for the prevention and treatment of various diseases, including cancer. However, research on this topic has led to inconclusive and often controversial results. This review aims to provide a comprehensive update of the effects and mechanisms related to the use of NHPs, to describe the results of randomized clinical trials (RCTs) on their effects in cancer patients, and to critically discuss factors influencing clinical outcomes. RCTs available in the literature, even those studying the same NHP, are very heterogeneous in terms of indications, doses, route and timing of administration, and outcomes evaluated. Silymarin, ginsenoside, and vitamin E appear to be useful in attenuating adverse events related to radiotherapy or chemotherapy, and curcumin and lycopene might provide some benefit in patients with prostate cancer. Most RCTs have not clarified whether NHP supplementation provides any real benefit, while harmful effects have been shown in some cases. Overall, the available data suggest that although there is some evidence to support the benefits of NHPs in the management of cancer patients, further clinical trials with the same design are needed before their introduction into clinical practice can be considered.

Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality of life. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in the pathogenesis of cisplatin-induced ototoxicity. Here, we investigated the effects of nuciferine, a natural active ingredient isolated from lotus species, on the ferroptosis of cochlear hair cells. Firstly, our results demonstrated that nuciferine can protect hair cells against RSL3-induced and cisplatin-induced damage. Secondly, nuciferine treatment reduced ferrous iron (Fe2+) overload in cochlear hair cells via inhibiting NCOA4-mediated ferritinophagy. Inhibition of ferritinophagy by knocking down Ncoa4 alleviated cisplatin-induced ototoxicity. Importantly, nuciferine treatment mitigated cochlear hair cell loss and damage to ribbon synapse, and improved mouse hearing function in an acute cisplatin-induced hearing loss model. Our findings highlight the role of NCOA4-mediated ferritinophagy in the pathogenesis of cisplatin-induced ototoxicity and provide evidence for nuciferine as a promising protective agent for treating cisplatin-induced hearing loss.

Hearing loss affects some nutrient intake. Disabling hearing loss may exacerbate these issues. We aimed to evaluate nutrient intake and assess deficiencies based on functional hearing status. The study included 6907 participants with information on demographic factors, nutrient intake, weight, height, disease status, and hearing level in the eighth Korea National Health and Nutrition Examination Survey, conducted from 2019 to 2021. We categorized the participants into 3 groups based on their functional hearing status: bilateral hearing, unilateral hearing, and disabling hearing loss. The disabling hearing loss group showed lower intake of most major nutrients (P < 0.05), dietary fiber (P < 0.001), and most minerals and vitamins (P < 0.05), with some insufficiencies. The unilateral hearing group showed lower intake only for potassium (P = 0.036) compared to the bilateral hearing group and significantly higher intake of hydration (P = 0.039), dietary fiber (P = 0.039), and calcium (P = 0.009) than the disabling hearing loss group. Nutrient insufficiency in the disabling hearing loss group was more prominent in women, and was partially resolved by using hearing aids. Clinicians and nutritionists should consider undernourishment in these patients, and appropriate interventions for nutrition and hearing aids should be recommended.

The combination of steroid structure and selenocyano group offers high potential for the design and synthesis of new potential anti-tumor drugs. Beginning with estradiol, a series of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives with remarkable antiproliferative activity was synthesized. Additionally, a 2,4-bisselenocyanoestradiol was synthesized by directly selenocyanating estradiol diacetate. It was found that the cytotoxicity of 2-selenocyano-3-selenocyanoalkyloxyestradiol derivatives was significantly increased in comparison to the corresponding monoselenocyanate precursor, whereas the cytotoxicity of the 2, 4-bisselenocyanoestradiol derivative was significantly reduced compared to the respective monosubstituted precursor. The introduction of the second selenocyano group at different locations of estradiol shows a various impact on the cytotoxicity of the compounds. Among them, compound 3e showed the best cytotoxicity, with an IC50 value of less than 5 μM against the tested tumor cells, and strong inhibitory activities against HeLa and MCF-7 cell xenograft tumors in zebrafish, suppressing tumor cell migration and neovascularization. Notably, compound 3e was more effective at inhibiting neovascularization of MCF-7 cell xenograft tumors than the positive control 2-methoxyestradiol. Furthermore, compound 3e showed excellent anti-oxidative stress effect in zebrafish. Therefore, these estrogen bisselenocyanate compounds may be promising anti-tumor agents, warranting further investigation.

Chemotherapy-related cognitive deficits (CRCI) as one of the common adverse drug reactions during chemotherapy that manifest as memory, attention, and executive function impairments. However, there are still no effective pharmacological therapies for the treatment of CRCI. Natural compounds have always inspired drug development and numerous natural products have shown potential therapeutic effects on CRCI. Nevertheless, improving the brain targeting of natural compounds in the treatment of CRCI is still a problem to be overcome at present and in the future. Accumulated evidence shows that nose-to-brain drug delivery may be an excellent carrier for natural compounds. Therefore, we reviewed natural products with potential anti-CRCI, focusing on the signaling pathway of these drugs' anti-CRCI effects, as well as the possibility and prospect of treating CRCI with natural compounds based on nose-to-brain drug delivery in the future. In conclusion, this review provides new insights to further explore natural products in the treatment of CRCI.

Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients.

Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.

Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions.

Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.

It is well known that platinum-based antineoplastic agents, including cisplatin (CP), have side effects that limit their use. Nefrotoxicity, neurotoxicity, and hemolytic anemia are the most common side effects. There are few studies on the reduction in these effects that involves nanoencapsulation; however, almost none involve cyclodextrins (CDs). Changes in the hematological and biochemical parameters of healthy Wistar rats treated with solutions of γ-cyclodextrin/resveratrol/cisplatin (γ-CD/Rv/CP) ternary complexes are investigated for the first time. They are intraperitoneally injected with γ-CD/Rv/CP solutions containing 5 mg CP/kg.b.w. Single shots were administered to six groups of Wistar rats (six individuals for every group) using γ-CD/Rv/CP, γ-CD/CP, γ-CD/Rv complexes, as well as positive- and negative-control groups, respectively. Thirty-two hematological and biochemical parameters were evaluated from blood samples and used as input variables for the principal component analysis (PCA) discrimination of the groups. The best protection was obtained for the γ-CD/Rv/CP ternary complex, which determined closer biochemical values to the control group. These values significantly differ from those of the γ-CD/CP treated group, especially for the IP, UA, and T-Pro kidney-related biochemical parameters. This finding proves the beneficial influence of Rv during CP administration through CD-based carriers.

Considering the rich background of Persian Medicine in the use of materia medica for the treatment of diseases, the huge burden of oral poisonings in the world, and the urgent need to find scientific solutions, the purpose of this study was to determine Avicenna's approach toward clinical toxicology and his proposed treatments for oral poisonings. In Al-Qanun Fi Al-Tibb, Avicenna addressed the materia medica for the treatments of oral poisonings after explaining the ingestion of different toxins and also elucidating the clinical toxicology approach toward poisoned patients. These materia medica were from different classes including emetics, purgatives, enemas, diaphoretics, antidiarrheals, inhaled drugs, sternutators, anticoagulants, antiepileptics, antitussives, diuretics, cooling drugs, stimulants, cardiotonic drugs, and heating oils. By applying different therapies, Avicenna endeavored to attain main goals in clinical toxicology that are comparable with modern medicine. They included removing the toxins from the body, decreasing the severity of the deleterious effects of toxins on the body, and counteracting the effects of toxins inside the body. Aside from introducing different therapeutic agents that played an important role in the treatment of oral poisonings, he emphasized the ameliorating effects of nutritive foods and beverages. Further research using other Persian medical resources is recommended to elucidate the applicable approaches and treatments for different poisonings.

Available studies on the effect of serum selenium levels on the risk of malignancies show some conflicting results. In this study, we investigated the correlation between serum selenium levels and ovarian cancer occurrence.

314 women (157 diseased patients and 157 healthy ones) matched in terms of age and BMI were included in the study. The measurements of selenium in the collected blood samples were performed using an ICP mass spectrometer. Univariable and multivariable analyzes were performed to determine the relationship between the factors under the study and the occurrence of ovarian cancer.

The mean concentration of selenium was lower among diseased ones than among controls (53.31 μg/L vs. 78.99 μg/L). A decrease in selenium concentration was noticed with the advancement of ovarian cancer. In univariable and multivariable analyzes, a clear relationship between low selenium concentration and the occurrence of ovarian cancer was found (35.3 (95% CI: 11.2-111; p < 0.001) and 45.8 (95% CI: 12.8-164; p < 0.001)).

The studied patients with ovarian cancer are characterized by statistically significant lower serum selenium levels than patients from the control group. Among the study group, a decrease in selenium concentration was observed with an increase in the FIGO stage. The determination of the role of selenium as a prophylactic factor in ovarian cancer requires further prospective studies.

Neoplasia of the head and the neck necessitates intervention, surgical or otherwise, as the site and stage of the pathology may dictate. The various therapeutic modalities employed and prognosis has been reviewed.

Obesity affects acute kidney injury (AKI) induced by various clinical settings, including transplantation and cisplatin-cancer therapy. However, the effect of short-term food intake change remains to be defined. Here, we investigated the effects of short-term high-fat diet intake and food restriction on cisplatin-induced AKI. Mice were fed either a high-fat diet (HFD) or a low-fat diet (LFD) for 11 days or were not fed for 40 hh (fasting), before cisplatin administration. Cisplatin-induced functional and structural damages to kidneys in both HFD- and LFD-fed mice, with greater damages in HFD-fed mice than LFD-fed mice. HFD decreased mitochondrial total glutathione (tGSH) level, along with increases in the plasma and kidney cholesterol levels. Cisplatin caused the increase of kidney cholesterol levels and oxidative stress, along with the decrease of mitochondrial tGSH levels. In addition, cisplatin-induced mitochondrial damage and apoptosis of tubular cells in both HFD- and LFD-fed mice. An increase of Fis1 (mitochondria fission 1 protein), whereas a decrease of Opa1 (mitochondria fusion 1 protein) occurred by cisplatin. These cisplatin effects were greater in HFD-fed mice than in LFD-fed mice. Administration of mitochondria-specific antioxidant treatment during HFD feeding inhibited these cisplatin-induced changes. Fasting for 40 h also significantly reduced the cisplatin-induced changes mentioned above. These data demonstrate that short-term HFD intake worsens cisplatin-induced oxidative stress by the reduction of mitochondrial tGSH, resulting in increased cisplatin-induced nephrotoxicity. These data newly indicate that the control of calorie intake, even for a short period, affects kidney susceptibility to injury. Although most studies described the effects of a long-term high-fat diet on the kidneys, in this study, we found that even if a high-fat diet was consumed for a short-term, physiological changes and mitochondria tGSH decrease in the kidneys, and consequently increased cisplatin-nephrotoxic susceptibility. These data suggest the association of calorie intake with kidney susceptibility to cisplatin.

Ellagic acid (EA) is a polyphenol compound abundant in berries, walnuts, pecans, pomegranate, cranberries, and other plant foods and exerts a wide array of biological properties. In particular, EA has received considerable research attention in anti-cancer therapy. EA administered alone has been shown to exert effects against human cancers through multiple pathways. In addition, EA may increase tumor sensitivity to chemotherapy and radiotherapy. Namely, EA combination with a relatively low dosage of therapeutic drugs or optimized radiation dose could improve the treatment outcome. More importantly, EA could counteract chemotherapy-related adverse reactions.

This review aims to summarize the in vitro and in vivo experimental evidence of synergism of EA in radiotherapy/chemotherapy for the treatment of cancers. In addition, the preventive effect of EA to counteract chemotherapy-induced toxicity is also discussed.

The searches were performed in the PubMed, Web of Science and Google scholar and introduced the information about the role of EA in cancer treatment.

EA exhibits synergistic effects in radiotherapy/chemotherapy for the treatment of cancers and exerts a great potential in reducing the side effects of chemotherapy and radiotherapy due to its biological activities, such as antioxidant and anti-inflammatory activities.

EA could be a promising drug adjuvant for cancer treatment. In the near future, novel strategies for EA delivery systems that overcome the low EA solubility and bioavailability should be studied further to fully exploit the therapeutic potential of EA.

The relationship between hearing impairment and nutrition has been extensively investigated; however, few studies have focused on this topic in working-age adults by income level. Herein, we aimed to determine the differences in hearing impairment among working-age adults by income level and identify the nutritional factors that affect hearing loss in various socioeconomic groups. Seven-hundred-and-twenty participants had hearing impairment, while 10,130 had normal hearing. After adjustment for propensity score matching, income and smoking status were identified as significant variables. By assessing the relationship between hearing impairment and nutrient intake by income level using multiple regression analyses, significant nutrients differed for each income category. Carbohydrate and vitamin C levels were significant in the low-income group; protein, fat, and vitamin B1 levels were significant in the middle-income group; and carbohydrates were significant in the high-income group. Income was significantly associated with hearing impairment in working-age adults. The proportion of individuals with hearing impairment increased as income decreased. The association between hearing impairment and nutritional intake also differed by income level. Our findings may enable the establishment of health policies for preventing hearing impairment in working-age adults by income level.

Cisplatin (cis-diamminedichloroplatinum II) is widely used for the treatment of cancer, but its cellular toxicity, especially in the form of oxidative stress, limits its use in multiple organs including the lungs. As a cellular organelle, cilia play an important role in cellular function and can be damaged by oxidative stress. However, the effect of cisplatin-induced lung toxicity on cilia has not yet been defined. Herein, we investigated the association of cilia and oxidative stress with cisplatin-induced lung damage.

Mice were administered with cisplatin. Some mice were treated with 2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito-TEMPO, a mitochondria-specific antioxidant) before the administration of cisplatin. Disruption of cilia was evaluated by the detection of ciliary proteins and fragments in the bronchoalveolar lavage fluid (BALF).

Cisplatin caused the thickening of interalveolar septa, infiltration of immune cells into the interalveolar septa, and increased protein concentration and total cell number in the BALF. Cisplatin also increased ciliary fragments and proteins in the BALF. In the lungs, cisplatin increased the production of hydrogen peroxide, lipid peroxidation, and apoptosis, while decreasing manganese superoxide dismutase, isocitrate dehydrogenase 2, and catalase expression. Treatment with Mito-TEMPO prevented cisplatin-induced lung damage, ciliary fragmentation, oxidative stress, and apoptosis.

By increasing oxidative stress in the lung, cisplatin induces lung cell damage, disruption of cilia, and release of disrupted cilia into the BALF. This suggests that cisplatin-induced lung damage can damage the cilia, manifesting as increased ciliary proteins in the BALF.

Cisplatin, an anticancer drug used in treating various types of cancers, can cause reproductive toxicities during chemotherapy. Keeping this in view, the present study was designed to investigate the possible protective effects of normal vitamin C and E and vitamin C and E nanoparticles (embedded in chitosan) against cisplatin-induced reproductive toxicities. Vitamins C, E, and their nanoparticles in this regard proved to be an effective therapy. The work aimed to treat cisplatin-induced reproductive toxicities through vitamin C and E and their nanoparticles. Cisplatin exposure caused significant reduction in the weight, testosterone level, and changed lipid profile. Similarly, cisplatin induced significant widespread testicular atrophy and testicular lesions as evidenced by the gaps in the epithelium and loss of differentiating germ cells. Vitamin C and E and their nanoparticles rescued the weight, testosterone level, and testicular disturbances, which is associated with improved histological view of testicular tissues. The current study highlights evidence that designing a medication of vitamin C and E nanoparticles is useful in mitigating cisplatin-induced reproductive toxicity in cancerous male patients underlying chemotherapy.

Colorectal carcinogenesis is the second most common cause of mortality across all types of malignancies, followed by hepatic and stomach cancers. Chemotherapy and radiotherapy are key approaches to treating cancer patients, but these carry major concerns, such as a high risk of side effects, poor accessibility, and the non-selective nature of chemotherapeutics. A number of natural products have been identified as countering various forms of cancer with fewer side effects. The potential impact of vitamins and minerals on long-term health, cognition, healthy development, bone formation, and aging has been supported by experimental and epidemiological studies. Successful treatment may thus be highly influenced by the nutritional status of patients. An insufficient diet could lead to detrimental effects on immune status and tolerance to treatment, affecting the ability of chemotherapy to destroy cancerous cells. In recent decades, most cancer patients have been taking vitamins and minerals to improve standard therapy and/or to decrease the undesirable side effects of the treatment together with the underlying disease. On the other hand, taking dietary supplements during cancer therapy may affect the effectiveness of chemotherapy. Thus, micronutrients in complementary oncology must be selected appropriately and should be taken at the right time. Here, the potential impact of micronutrients on gastro-intestinal and hepatic cancers is explored and their molecular targets are laid down.

Cognitive impairment is one of the most deleterious effects of chemotherapy treatment in cancer patients, and this problem sometimes remains even after chemotherapy ends. Common classes of chemotherapy-based regimens such as anthracyclines, taxanes, and platinum derivatives can induce both oxidative stress in the blood and in the brain, and these effects can be reproduced in neuronal and glia cell cultures. In rodent models, both the acute and repeated administration of doxorubicin or adriamycin (anthracyclines) or cisplatin impairs cognitive functions, as shown by their diminished performance in different learning and memory behavioural tasks. Administration of compounds with strong antioxidant effects such as N-acetylcysteine, gamma-glutamyl cysteine ethyl ester, polydatin, caffeic acid phenethyl ester, and 2-mercaptoethane sulfonate sodium (MESNA) counteract both oxidative stress and cognitive alterations induced by chemotherapeutic drugs. These antioxidant molecules provide the scientific basis to design clinical trials in patients with the aim of reducing the oxidative stress and cognitive alterations, among other probable central nervous system changes, elicited by chemotherapy in cancer patients. In particular, N-acetylcysteine and MESNA are currently used in clinical settings and are therefore attracting scientific attention.

Cisplatin has been a mainstay of cancer chemotherapy since the 1970s. Despite its broad anticancer potential, its clinical use has regularly been constrained by kidney toxicities. This review details those biochemical pathways and metabolic conversions that underlie the kidney toxicities. A wide range of redox events contribute to the eventual physiological consequences of drug activities.

Cisplatin (CP), one of the most commonly used antitumor drugs in clinic, could induce reproductive and genetic toxicity. Traditional Chinese medicine believed that this side effect might be caused by the deficiency of both qi and blood. Panax notoginseng (Burk.) F. H. Chen (PN) is a traditional precious Chinese medicine for nourishing blood and hemostasis, which had the synergistic antitumor and reducing toxicity effects. However, the protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity were still unknown.

This study was designed to illuminate the possible protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity.

Network pharmacology was first applied to analyze the potential components and targets of PN against CP-induced reproductive and genetic toxicity. Then, the results of network pharmacology were validated in a mouse model of reproductive and genotoxicity induced by CP. Body weight, testis weight, epididymis weight, sperm count, sperm viability and sperm morphology were used to assess protective effects of PN on CP-induced reproductive toxicity. Tail moment in peripheral blood cells and micronucleus in bone marrow cells were used to assess protective effects of PN on CP-induced genetic toxicity. Finally, possible protective targets obtained from network pharmacology, including 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), were experimentally validated by ELISA.

One hundred and nineteen components of PN and sixty-eight targets of reproductive/genetic toxicity were acquired and constituted as the component-target network. Network pharmacology analysis showed alleviating oxidative stress might play important role in therapeutic mechanism of PN. In verified experiments, PN significantly improved the decline of body weight, testis weight and epididymis weight, increased sperm count and viability, decreased abnormal sperm morphology rate induced by CP in mice. Moreover, PN also significantly decreased the tail moment in peripheral blood cells and micronucleus formation rate in bone marrow cells in CP-induced mice. Finally, not only the decrease of T-SOD and GSH-Px level but also the increase of 8-OHdG and MDA level in serum were restored under PN treatment.

Current study found that PN could improve CP-induced reproductive and genetic toxicity, which were probably attributed to alleviating oxidative stress. This finding provided the new perspective for understanding the therapeutic effect of PN on CP-induced reproductive and genetic toxicity and facilitating the clinical use of PN.

Chemotherapy and radiotherapy are the most frequent treatment for patients suffering from malignant progression of cancer. Even though new treatments are now being implemented, administration of these chemotherapeutic agents remains as the first line option in many tumor types. However, the secondary effects of these compounds represent one of the main reasons cancer patients lose life quality during disease progression. Recent data suggests that Ocoxin, a plant extract and natural compound based nutritional complement rich in antioxidants and anti-inflammatory mediators exerts a positive effect in patients receiving chemotherapy and radiotherapy. This mixture attenuates the chemotherapy and radiotherapy-related side effects such as radiation-induced skin burns and mucositis, chemotherapy-related diarrhea, hepatic toxicity and blood-infection. Moreover, it has been proven to be effective as anticancer agent in different tumor models both in vitro and in vivo, potentiating the cytotoxic effect of several chemotherapy compounds such as Lapatinib, Gemcitabine, Paclitaxel, Sorafenib and Irinotecan. The aim of this review is to put some light on the potential of this nutritional mixture as an anticancer agent and complement for the standard chemotherapy routine.

Although great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy.

This review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications.

We obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects.

Representative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values.

This review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.

Herniarin is a member of simple coumarins, which are a group of common secondary metabolites in plants. The aim of the present study was to investigate the effects of herniarin on genotoxicity and apoptosis induced by cisplatin in rat bone marrow cells. The experimental rats were treated with four different doses of herniarin (50, 100, 200, and 400 mg/kg.) for seven consecutive days. The cisplatin (5 mg/kg, i.p.) was injected into mice 1 h after the last oral herniarin administration on the seventh day. The protective effects of herniarin were investigated by hematological test, flow cytometry, micronucleus assay, and reactive oxygen species (ROS) level analysis. Herniarin caused a marked reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after exposure to cisplatin at doses of 200 and 400 mg/kg. Furthermore, herniarin significantly increased the levels of both red and white blood cells in peripheral blood. Treatment of rats with herniarin before cisplatin, significantly decreased the percentage of apoptotic and necrotic cells and the ROS level in bone marrow cells. This study indicated that herniarin can be introduced as a new chemoprotective agent against cisplatin-induced genotoxicity in the future.

Cisplatin is a highly effective chemotherapeutic agent against a variety of solid tumors in adults and in children. Unfortunately, a large percentage of patients suffer permanent sensorineural hearing loss. Up to 60% of children and at least 50% of adults suffer this complication that seriously compromises their quality of life. Hearing loss is due to damage to the sensory cells in the inner ear. The mechanisms of cochlear damage are still being investigated. However, it appears that inner ear damage is triggered by reactive oxygen species (ROS) formation and inflammation 34.

We discuss a number of potential therapeutic targets that can be addressed to provide hearing protection. These strategies include enhancing the endogenous antioxidant pathways, heat shock proteins, G protein coupled receptors and counteracting ROS and reactive nitrogen species, and blocking pathways that produce inflammation, including TRPV1 and STAT1 36.

Numerous potential protective agents show promise in animal models by systemic or local administration. However, clinical trials have not shown much efficacy to date with the exception of sodium thiosulfate. There is an urgent need to discover safe and effective protective agents that do not interfere with the efficacy of cisplatin against tumors yet preserve hearing 151.

Severe durable changes may occur to the DNA structure caused by exogenous and endogenous risk factors initiating the process of carcinogenesis. By evidence, a large portion of malignancies have been demonstrated as being preventable. Moreover, the targeted prevention of cancer onset is possible, due to unique properties of plant bioactive compounds. Although genoprotective effects of phytochemicals have been well documented, there is an evident lack of articles which would systematically present the spectrum of anticancer effects by phytochemicals, plant extracts, and plant-derived diet applicable to stratified patient groups at the level of targeted primary (cancer development) and secondary (cancer progression and metastatic disease) prevention. Consequently, clinical implementation of knowledge accumulated in the area is still highly restricted. To stimulate coherent co-development of the dedicated plant bioactive compound investigation on one hand and comprehensive cancer preventive strategies on the other hand, the current paper highlights and deeply analyses relevant evidence available in the area. Key molecular mechanisms are presented to detail genoprotective and anticancer activities of plants and phytochemicals. Clinical implementation is discussed. Based on the presented evidence, advanced chemopreventive strategies in the context of 3P medicine are considered.

Cisplatin is an effective chemotherapeutic agent that has pronounced adverse effects. Using flavonoids is currently eliciting considerable interest. During extraction and conditioning, they usually undergo several physical treatments such as heat treatment, although it is not known whether thermal treatment might influence the pharmacological effects of flavonoids such as luteolin-7-O-glucoside (L7G). This study was undertaken to explore the protective role of native and heated L7G against DNA damage and oxidative stress induced by cisplatin. Balb/c mice were administered L7G before a single intraperitoneal injection of cisplatin (10 mg/kg). Animals were sacrificed 24 h after treatment with drugs. The geno-protective role of native and heated L7G was evaluated by comet assay. In addition to monitoring the activities of antioxidant enzymes, levels of malondialdehyde and reduced glutathione were assessed in the liver, kidney, brain, and spleen tissues. The results of the present study demonstrate that both heated and native L7G, at a dose of 40 mg/kg b.w, were able to reduce the genotoxicity of cisplatin. They attenuate the oxidative stress (malondialdehyde, catalase, GPx, SOD, and GSH) and tissue damage (creatinine, IFNγ). Heat treatment did not alter the antigenotoxic effect observed for native L7G and showed similar effects to those of native L7G for all of the evaluated parameters. Our study reveals that L7G attenuates the side effects of anticancer drug and heat treatment did not alter his antigenotoxic and antioxidant the potential.

Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20-40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA.

We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018, without language restriction. All studies (observational and interventional) assessing a CIA prevention method for adults receiving at least one course of cisplatin were eligible. The primary outcome was acute nephrotoxicity, as defined by the AKI-KDIGO classification (2012). The odds ratio and corresponding 95% confidence interval were used to assess the associations. We used narrative synthesis in case of heterogeneity regarding intervention, population, or outcome. When possible, a random-effects model was used to pool studies. The heterogeneity between studies was quantified (I²), and multiple meta-regressions were carried out to identify potential confounders.

Within 4520 eligible studies, 51 articles fulfilling the selection criteria were included in the review, assessing 21 different prevention methods. A meta-analysis could only be performed on the 15 observational studies concerning magnesium supplementation (1841 patients), and showed a significant nephroprotective effect for all combined grades of CIA (OR 0.24, [0.19-0.32], I² = 0.0%). This significant nephroprotective effect was also observed for grades 2 and 3 CIA (OR 0.22, [0.14-0.33], I² = 0.0% and OR 0.25, [0.08-0.76], I² = 0.0%, respectively).

While no method of prevention had so far demonstrated its indisputable efficacy, our results highlight the potential protective effect of magnesium supplementation on cisplatin-induced acute nephrotoxicity.

This study is registered in PROSPERO, CRD42018090612.

Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.

The use of cisplatin (CP) in chemotherapy of resistant cancers is limited due to its dose-dependent nephrotoxicity. Disulfiram (DSF), the aversion therapy for alcoholism, has recently emerged as an anticancer and chemopreventive agent. Its anticancer activity is potentiated in the presence of copper. However, such use of copper leads to several adverse effects. In the present study, the protective effect of DSF and its copper chelate (Cu-DEDC) against CP-induced nephrotoxicity in rats was evaluated. Nephrotoxicity was induced by a single intraperitoneal injection of CP (5 mg/kg). The treatment groups included control (vehicle treated), CP (CP-treated), CP + DSF (CP followed by DSF), CP + DSF + Cu (CP followed by DSF and CuCl₂), CP + Cu-DEDC (CP followed by Cu-DEDC), and CP + AMF (amifostine pre-treated and CP-treated). The DSF, Cu-DEDC, and CuCl₂ were administered orally at 50 mM/kg/day dose for 5 days post CP injection. AMF served as a standard chemo protectant, administered intravenously 30 min prior to CP. The markers of oxidative stress, inflammation, and kidney function estimated on the 6th day revealed that both DSF and Cu-DEDC significantly attenuated the CP-induced rise in the serum/urine creatinine and blood urea nitrogen (BUN). The CP-induced rise in serum alkaline phosphatase (ALPase) was reversed by these drugs. Both drugs reduced the levels of malondialdehyde and nitric oxide (NO) in kidney tissues. These drugs reversed CP-induced depletion of SOD, catalase, and GSH in the kidneys. There was a significant reduction in the CP-induced TNF-α and IL-1β production along with prevention of histological alterations. Above observations indicate that DSF and Cu-DEDC may have significance as adjuvants to protect against CP-induced nephrotoxicity.

Cisplatin is a potent antineoplastic drug that has been widely used to treat a number of solid tumors. However, a high incidence of renal damage observed in patients has led researchers to search for alternate strategies that prevent or at least reduce the cisplatin-induced nephrotoxicity. The objective of the present study was to conduct a systematic review and a subsequent meta-analysis to evaluate and identify compounds with effective antitumor activity and lesser side effects that could provide protection against cisplatin-induced nephrotoxicity.

The study included all placebo-controlled trials published up to December 2017 that met the inclusion criteria. A total of 22 articles were finally included to extract the following information: number of patients, doses of cisplatin and protectant, qualitative (acute kidney injury incidence) and quantitative (plasma creatinine, blood urea nitrogen, and creatinine clearance) indicators of renal function. The odds ratio or the mean difference (95% confidence interval) of each parameter was calculated for each study and group of studies.

The results of this meta-analysis show that there is great variability in the nephroprotective capacity of a variety of products evaluated. Of all the compounds tested, only magnesium sulfate and cystone were found to exert protective effects. However, more studies need to be conducted to confirm these results.

The administration of 1 g of Mg i.v. seems to be the best strategy for the prevention of cisplatin nephrotoxicity.

Autophagy has been demonstrated to be vital for kidney homeostasis and is centrally implicated in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Lithium is a potent autophagy inducer in a number of cell types. However, it remains uncertain whether its autophagic activity is associated with a beneficial effect on renal tubular cells in AKI. This study aimed to examine the effect of lithium on renal autophagy in cisplatin-induced AKI. Mice or renal proximal tubular epithelial cells in culture were exposed to cisplatin-induced acute injury in the presence or absence of lithium treatment. AKI or tubular cell injury was evaluated, and cell signaling associated with autophagy was examined. Lithium pretreatment prominently ameliorated acute renal tubular damage in mice exposed to cisplatin insult, associated with enhanced autophagy in renal tubules, as assessed by measuring microtubule-associated protein 1A/1B-light chain 3 (LC3)BII/I expression and autophagosome formation. Consistently, in cisplatin-injured renal tubular cells in vitro, lithium enhanced autophagic activities, improved cell viability, and attenuated cell death. Mechanistically, lithium triggered AMPK-α phosphorylation and activation, which in turn positively correlated with the induced expression of autophagy-related molecules, like mammalian target of rapamycin and LC3BII/I. AMPK-α activation is likely required for lithium-induced tubular cell autophagy and protection in cisplatin-induced AKI because blockade of AMPK-α phosphorylation by compound C markedly abrogated lithium-induced autophagosome formation and mitigated the protective effect of lithium on AKI. Our findings suggest that lithium represents a promising therapeutic strategy for protecting renal tubular cells against cisplatin-induced AKI by enhancing autophagy via AMPK-α activation.-Bao, H., Zhang, Q., Liu, X., Song, Y., Li, X., Wang, Z., Li, C., Peng, A., Gong, R. Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells.

The identification of preventive interventions that are safe and effective for cisplatin-induced ototoxicity is important, especially in children because hearing loss can impair speech-language acquisition development. Previous randomised trials assessed systemic drugs such as amifostine, sodium diethyldithiocarbamate or disulfiram, and sodium thiosulfate. Amifostine, sodium diethyldithiocarbamate, and disulfiram did not show hearing preservation. Paediatric trials assessing sodium thiosulfate showed efficacy in terms of hearing protection. The SIOPEL 6 trial consisted solely of patients with localised hepatoblastoma and no effects on survival were shown. In the ACCL0431 trial, which included heterogeneous patients, a post-hoc analysis showed significantly worse overall survival among patients who had disseminated disease receiving sodium thiosulfate than among controls, but not among those with localised disease. Intratympanically administered drugs have mainly been assessed in adults and include N-acetylcysteine and dexamethasone. Inconsistent effects of these drugs were identified but these studies were limited by design, small sample size, and statistical approach. Future studies of systemic drugs will need to consider the measurement of disease outcomes through study design and sample size, and ototoxicity endpoints should be harmonised to enhance comparability between trials.

Cisplatin is one of the highly consumed and effective antitumor agents whose clinical application is accompanied by nephrotoxicity adverse reaction. Also, other complications such as ototoxicity and hepatotoxicity are a matter of concern. Today, it is suggested that cisplatin-associated toxicities are mainly induced by free radicals production, which will result in oxidative organ injury. The evidence is growing over the protective effects of antioxidants on cisplatin-induced adverse reactions especially nephrotoxicity. The possible protective effects of vitamin E and its derivative in cisplatin-induced nephrotoxicity and ototoxicity are reviewed here at the light of pertinent results from basic and clinical research. Administration of vitamin E alone or in combination with other antioxidant agents could cause amelioration in oxidative stress biomarkers such as decreasing the level of malondialdehyde, reducing serum urea and creatinine, and also enhancing the activities of renal antioxidant enzymes including renal catalase, glutathione-S-transferase, and superoxide dismutase. Although the data from most of the studies are in favors of protective effects of vitamin E against cisplatin-induced toxicity, more clinical trials are needed to clarify the clinical importance of vitamin E administration as an antioxidant during cisplatin therapy in cancer condition.

Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. One of the most significant adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied. This review is the third update of a previously published Cochrane Review.

To assess the efficacy of medical interventions to prevent hearing loss and to determine possible effects of these interventions on antitumour efficacy, toxicities other than hearing loss and quality of life in children with cancer treated with platinum-based therapy as compared to placebo, no additional treatment or another protective medical intervention.

We searched the Cochrane Central Register of Controlled Trials, MEDLINE (PubMed) and Embase (Ovid) to 8 January 2019. We handsearched reference lists of relevant articles and assessed the conference proceedings of the International Society for Paediatric Oncology (2006 up to and including 2018), the American Society of Pediatric Hematology/Oncology (2007 up to and including 2018) and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (2010 up to and including 2015). We scanned ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP; apps.who.int/trialsearch) for ongoing trials (on 2 January 2019).

Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) evaluating platinum-based therapy with an otoprotective medical intervention versus platinum-based therapy with placebo, no additional treatment or another protective medical intervention in children with cancer.

Two review authors independently performed the study selection, data extraction, risk of bias assessment and GRADE assessment of included studies, including adverse effects. We performed analyses according to the Cochrane Handbook for Systematic Reviews of Interventions.

We identified two RCTs and one CCT (total number of participants 149) evaluating the use of amifostine versus no additional treatment in the original version of the review; the updates identified no additional studies. Two studies included children with osteosarcoma, and the other study included children with hepatoblastoma. Children received cisplatin only or a combination of cisplatin and carboplatin, either intra-arterially or intravenously. Pooling of results of the included studies was not possible. From individual studies the effect of amifostine on symptomatic ototoxicity only (i.e. National Cancer Institute Common Toxicity Criteria version 2 (NCICTCv2) or modified Brock grade 2 or higher) and combined asymptomatic and symptomatic ototoxicity (i.e. NCICTCv2 or modified Brock grade 1 or higher) were uncertain (low-certainty evidence). Only one study including children with osteosarcoma treated with intra-arterial cisplatin provided information on tumour response, defined as the number of participants with a good or partial remission. The available-data analysis (data were missing for one participant), best-case scenario analysis and worst-case scenario analysis showed a difference in favour of amifostine, although the certainty of evidence for this effect was low. There was no information on survival for any of the included studies. Only one study, including children with osteosarcoma treated with intra-arterial cisplatin, provided data on the number of participants with adverse effects other than ototoxicity grade 3 or higher (on NCICTCv2 scale). There was low-certainty evidence that grade 3 or 4 vomiting was higher with amifostine (risk ratio (RR) 9.04, 95% confidence interval (CI) 1.99 to 41.12). The effects on cardiotoxicity and renal toxicity grade 3 or 4 were uncertain (low-certainty evidence). None of the studies evaluated quality of life.In the recent update, we also identified one RCT including 109 children with localized hepatoblastoma evaluating the use of sodium thiosulfate versus no additional treatment. Children received intravenous cisplatin only (one child also received carboplatin). There was moderate-certainty evidence that both symptomatic ototoxicity only (i.e. Brock criteria grade 2 or higher) and combined asymptomatic and symptomatic ototoxicity (i.e. Brock criteria grade 1 or higher) was lower with sodium thiosulfate (combined asymptomatic and symptomatic ototoxicity: RR 0.52, 95% CI 0.33 to 0.81; symptomatic ototoxicity only: RR 0.39, 95% CI 0.19 to 0.83). The effect of sodium thiosulfate on tumour response (defined as number of participants with a complete or partial response at the end of treatment), overall survival (calculated from time of randomization to death or last follow-up), event-free survival (calculated from time of randomization until disease progression, disease relapse, second primary cancer, death, or last follow-up, whichever came first) and adverse effects other than hearing loss and tinnitus grade 3 or higher (according to National Cancer Institute Common Toxicity Criteria Adverse Effects version 3 (NCICTCAEv3) criteria) was uncertain (low-certainty evidence for all these outcomes). Quality of life was not assessed.We found no eligible studies for possible otoprotective medical interventions other than amifostine and sodium thiosulfate and for other types of malignancies.

At the moment there is no evidence from individual studies in children with osteosarcoma or hepatoblastoma treated with different platinum analogues and dosage schedules that underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment. Since pooling of results was not possible and the evidence was of low certainty, no definitive conclusions can be made. Since we found only one RCT evaluating the use of sodium thiosulfate in children with localized hepatoblastoma treated with cisplatin, no definitive conclusions on benefits and harms can be drawn. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. We identified no eligible studies for other possible otoprotective medical interventions and other types of malignancies, so no conclusions can be made about their efficacy in preventing ototoxicity in children treated with platinum-based therapy. More high-quality research is needed.

The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin-induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double-blind, placebo-controlled trial conducted in patients receiving high-dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro-, oto-, hepato-, myelo-, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty-seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low-dose oral NAC does not protect patients with head and neck cancer from cisplatin-induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC.