|
1
|
Prajapati J, Bhatt N, Rawal R. Hepatoprotective effects of phytochemicals and plant extracts against chemotherapy-induced liver damage in animal models: a systematic review. Arch Toxicol 2025; 99:887-914. [PMID: 39729113 DOI: 10.1007/s00204-024-03928-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 11/28/2024] [Indexed: 12/28/2024]
Abstract
Chemotherapy, a cornerstone of cancer treatment, is frequently marred by its hepatotoxic effects, which can significantly impede therapeutic efficacy. This systematic review meticulously evaluates the hepatoprotective properties of phytochemicals and plant extracts against chemotherapy-induced liver damage, primarily in experimental animal models. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an exhaustive search was conducted across databases like SCOPUS, PubMed, and Web of Science, culminating in the inclusion of 61 pertinent studies. These studies illustrate those natural compounds, spanning a diverse array of phytochemicals and plant extracts that can effectively mitigate biochemical markers of liver damage, enhance antioxidant defences, and modulate inflammatory responses in model organisms subjected to hepatotoxic chemotherapeutic agents such as cyclophosphamide, cisplatin, and doxorubicin. Notably, the natural agents reviewed have demonstrated significant reductions in liver enzymes, improved histopathological outcomes, and bolstered cellular antioxidant capacities. The systematic synthesis of data underscores the potential of these natural substances to diminish liver toxicity associated with chemotherapy in preclinical settings. However, the review also highlights critical gaps in research, notably the underreporting of molecular mechanisms and inconsistent data on clinical translatability. To optimize the therapeutic utility of these compounds, future studies should focus on detailed molecular analyses and rigorous clinical trials to validate efficacy and safety, paving the way for integrated approaches in oncological care that minimize hepatic complications.
Collapse
Affiliation(s)
- Jignesh Prajapati
- Department of Biochemistry and Forensic Science, University School of Sciences, Gujarat University, Ahmedabad, 380009, Gujarat, India
- INVENTAYU Private Limited, AIC-LMCP Foundation, L. M. College of Pharmacy, Navrangpura, Ahmedabad, 380009, Gujarat, India
| | - Narendra Bhatt
- INVENTAYU Private Limited, AIC-LMCP Foundation, L. M. College of Pharmacy, Navrangpura, Ahmedabad, 380009, Gujarat, India.
| | - Rakesh Rawal
- Department of Medical Biotechnology, Gujarat Biotechnology University, GIFT City, Gandhinagar, 382355, Gujarat, India.
| |
Collapse
|
|
2
|
Fu K, Wang C, Ma C, Zhou H, Li Y. The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity. Front Pharmacol 2021; 12:771459. [PMID: 34803712 PMCID: PMC8600187 DOI: 10.3389/fphar.2021.771459] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022] Open
Abstract
Liver diseases have been a common challenge for people all over the world, which threatens the quality of life and safety of hundreds of millions of patients. China is a major country with liver diseases. Metabolic associated fatty liver disease, hepatitis B virus and alcoholic liver disease are the three most common liver diseases in our country, and the number of patients with liver cancer is increasing. Therefore, finding effective drugs to treat liver disease has become an urgent task. Chinese medicine (CM) has the advantages of low cost, high safety, and various biological activities, which is an important factor for the prevention and treatment of liver diseases. This review systematically summarizes the potential of CM in the treatment of liver diseases, showing that CM can alleviate liver diseases by regulating lipid metabolism, bile acid metabolism, immune function, and gut microbiota, as well as exerting anti-liver injury, anti-oxidation, and anti-hepatitis virus effects. Among them, Keap1/Nrf2, TGF-β/SMADS, p38 MAPK, NF-κB/IκBα, NF-κB-NLRP3, PI3K/Akt, TLR4-MyD88-NF-κB and IL-6/STAT3 signaling pathways are mainly involved. In conclusion, CM is very likely to be a potential candidate for liver disease treatment based on modern phytochemistry, pharmacology, and genomeproteomics, which needs more clinical trials to further clarify its importance in the treatment of liver diseases.
Collapse
Affiliation(s)
| | | | | | | | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| |
Collapse
|
|
3
|
Cavalloro V, Bracco F, Collina S, Martino E. Focus on Phytochemical and Pharmacological Profile of Prunus lycioides (=Amygdalus lycioides). Mini Rev Med Chem 2020; 20:2207-2214. [PMID: 32744969 DOI: 10.2174/1389557520666200730153653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 05/06/2020] [Accepted: 05/22/2020] [Indexed: 11/22/2022]
Abstract
Prunus lycioides (Spach) C.K. Schneid. (= Amygdalus lycioides Spach.), popularly recognized as "Badam Talkh kuhi", is an endemic species of Iran. It is widely distributed in Central and West Asia, where it plays a role in preventing and controlling soil erosion. Although domestic species of Prunus genus are well known and widely used in food, pharmaceutical, and cosmetic industries, inadequate information about wild species is available so far. As far as Prunus lycioides, it is commonly used by native people in traditional medicine for treating diabetes, inflammatory diseases, and microbial infections. The wild almonds are traditionally exploited for oil extraction due to their antioxidant properties. This review summarizes advances in the studies regarding Prunus lycioides and its pharmacological properties. The aim of the review is to renew the interest in this promising plant, thus stimulating researchers to go further with the study for discovering new bioactive compounds.
Collapse
Affiliation(s)
- Valeria Cavalloro
- Department of Earth and Environmental Sciences, University of Pavia, Pavia, Italy
| | - Francesco Bracco
- Department of Earth and Environmental Sciences, University of Pavia, Pavia, Italy
| | - Simona Collina
- Department of Drug Sciences, Medicinal Chemistry Section, University of Pavia, Pavia, Italy
| | - Emanuela Martino
- Department of Earth and Environmental Sciences, University of Pavia, Pavia, Italy
| |
Collapse
|
|
4
|
Kim HJ, Park KK, Chung WY, Lee SK, Kim KR. Protective Effect of White-fleshed Peach ( Prunus persica (L.) Batsch) on Chronic Nicotine-induced Toxicity. J Cancer Prev 2017; 22:22-32. [PMID: 28382283 PMCID: PMC5380186 DOI: 10.15430/jcp.2017.22.1.22] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 02/28/2017] [Accepted: 03/01/2017] [Indexed: 11/04/2022] Open
Abstract
Background Nicotine is a major toxic component of tobacco smoke and has been recognized as a risk factor to induce oxidative tissue damage, which is a precursor to cardiovascular diseases, lung-related diseases, and cancers. Peaches (Prunus persica) have been used for the treatment of degenerative disorders, such as hypermenorrhea, dysmenorrhea, and infertility in Asian countries. In this study, we investigated the effects of white-fleshed peach on the excretion of nicotine metabolites and 1-hydroxypyrene in smokers and chronic nicotine-induced tissue damages in mice. Methods The concentrations of cotinine and 1-hydroxypyrene were measured in urine of smokers before or after intake of white-fleshed peaches. In addition, ICR mice were injected with nicotine (5 mg/kg body weight) and then orally administered with white-fleshed peach extracts (WFPE) (250 or 500 mg/kg body weight) for 36 days. The oxidative stress parameters and the activities of antioxidant enzymes were measured in liver and kidney tissues. Also, histological changes and nitrotyrosine expression were assessed. Results Intake of white-fleshed peaches increased the urinary concentration of nicotine metabolites and 1-hydroxypyrene in 91.67% and 83.33% of smokers, respectively. WFPE decreased the malondialdehyde levels and recovered the activities of antioxidant enzymes in nicotine-injected mice. In addition, WFPE inhibited nitrotyrosine expression and inflammatory responses in the liver, kidney, and lung tissues of nicotine-treated mice. Conclusions White-fleshed peaches may increase the metabolism of toxic components in tobacco smoke in smokers and protect normal tissues against nicotine toxicity in mice. Therefore, supplementation of white-fleshed peaches might be beneficial to smokers.
Collapse
Affiliation(s)
- Hyun-Jeong Kim
- Department of Oral Biology and Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea
| | - Kwang-Kyun Park
- Department of Oral Biology and Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Korea
| | - Won-Yoon Chung
- Department of Oral Biology and Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Korea
| | - Sun Kyoung Lee
- Department of Oral Biology and Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea
| | - Ki-Rim Kim
- Department of Dental Hygiene, Kyungpook National University, Sangju, Korea
| |
Collapse
|
|
5
|
Heidari-Soreshjani S, Asadi-Samani M, Yang Q, Saeedi-Boroujeni A. Phytotherapy of nephrotoxicity-induced by cancer drugs: an updated review. J Nephropathol 2017; 6:254-263. [PMID: 28975109 PMCID: PMC5607991 DOI: 10.15171/jnp.2017.41] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 01/27/2017] [Indexed: 12/15/2022] Open
Abstract
Context:
Kidney is one of the vital organs maintaining homeostasis of body and thus
dysfunction of kidney affects quality of life and health severely. Anticancer drugs,
particularly chemotherapeutic agents, cause high toxicity leading kidney dysfunction
and irreparable kidney injury. Therefore, attention has recently been paid to seeking out
alternatives such as nature-based drugs that are effective but less toxic. In this regard, this
systematic review article is to report and introduce the most important medicinal plants
and their derivatives that are used to reduce anticancer drug-induced nephrotoxicity.
Evidence Acquisitions: The word nephrotoxicity alongside the words cancer or chemotherapy
in combination with some herbal terms such as medicinal plant, plants, herbs, and extracts
were administered to search for relevant publications indexed in PubMed.
Results:
According to this study, 16 medicinal plants, 12 plant-based derivatives, and three
traditional plant-based formulations were found to help control and modulate anticancer
drug-induced nephrotoxicity indices.
Conclusions:
Anticancer drugs cause nephrotoxicity through activating pathways of oxidative
stress, damage-associated molecular patterns (DAMPs) production, inflammatory
processes, and cell apoptosis, while medicinal plants and their derivatives can cause
reduction in nephrotoxicity and anticancer drugs side effects via their antioxidant and
anti-inflammatory properties.
Collapse
Affiliation(s)
| | - Majid Asadi-Samani
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Qian Yang
- Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany
| | - Ali Saeedi-Boroujeni
- Department of Immunology, School of Medicine, Jundishapur University of Medical Sciences, Ahvaz, Iran
| |
Collapse
|
|
6
|
Zhang Y, Luo JX, Hu XY, Yang F, Zhong S, Lin W. Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats. World J Gastroenterol 2016; 22:2558-2565. [PMID: 26937143 PMCID: PMC4768201 DOI: 10.3748/wjg.v22.i8.2558] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 10/13/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats.
METHODS: Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed.
RESULTS: D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/β-actin (0.06 ± 0.03, 0.11 ± 0.04 vs 0.25 ± 0.04, P < 0.05); TLR4 mRNA/β-actin (0.07 ± 0.02, 0.22 ± 0.08 vs 0.41 ± 0.22, P < 0.05); NF-κB mRNA/β-actin (0.74 ± 0.41, 1.78 ± 0.64 vs 2.68 ± 1.35, P < 0.05); and caspase-3 mRNA/β-actin levels were all significantly reduced (1.61 ± 0.45, 2.57 ± 1.04 vs 3.41 ± 0.85, P < 0.05). The gene expression levels were significantly lower in the IPTT group than in the SNMC group (P < 0.05). Compared with the model group, the PCNA expression in liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 ± 4.91, 25.57 ± 2.94 vs 17.55 ± 2.40, P < 0.05).
CONCLUSION: IPTT attenuates inflammation in ALF via inhibition of HMGB1 production, which may contribute to limited liver regeneration.
Collapse
|
|
7
|
Park D, Jo IG, Jang JY, Kwak TH, Yoo SK, Jeon JH, Choi EK, Joo SS, Kim O, Kim YB. A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis. Biomol Ther (Seoul) 2015; 23:449-457. [PMID: 26336585 PMCID: PMC4556205 DOI: 10.4062/biomolther.2015.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 04/29/2015] [Accepted: 05/06/2015] [Indexed: 01/12/2023] Open
Abstract
The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.
Collapse
Affiliation(s)
- Dongsun Park
- College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763
- Department of Physiology, Ajou University School of Medicine, Suwon 443-749,
Republic of Korea
| | - In Geun Jo
- College of Pharmacy, Advanced Science, Dankook University, Cheonan 330-714
| | - Ja Young Jang
- College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763
| | - Tae Hwan Kwak
- KT&G Life Science Corporation R&D Center, Suwon 443-702
| | - Sang Ku Yoo
- Erum Biotechnologies Incorporation, Suwon 443-380
| | - Jeong Hee Jeon
- College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763
| | - Ehn-Kyoung Choi
- College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763
| | - Seong Soo Joo
- Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University, Gangneung 210-702
| | - Okjin Kim
- College of Natural Resources, Wonkwang University, Iksan 570-749
| | - Yun-Bae Kim
- College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763
| |
Collapse
|
|
8
|
Tinospora cordifolia as a protective and immunomodulatory agent in combination with cisplatin against murine visceral leishmaniasis. Exp Parasitol 2013; 137:53-65. [PMID: 24370645 DOI: 10.1016/j.exppara.2013.12.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Revised: 12/11/2013] [Accepted: 12/16/2013] [Indexed: 12/11/2022]
Abstract
Effect of pure herb, Tinospora cordifolia was studied for its hepatoprotective, nephroprotective and immunomodulatory activity against high dose cisplatin treatment in Leishmania donovani infected BALB/c mice. Administration of cisplatin (5mg/kg b.wt. daily for 5 days, i.p.) reduced the parasite load in L. donovani infected BALB/c mice but produced damage in liver and kidney as manifested biochemically by an increase in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum urea, serum creatinine and various electrolytes etc. These biochemical analyses were further supported by cisplatin induced morphological changes in kidney, liver and spleen. To combat this pure herb, T. cordifolia (100mg/kg b.wt. for 15 days daily) was used in combination with cisplatin in L. donovani infected BALB/c mice and it was found that all the aforementioned changes were effectively attenuated by T. cordifolia when administered in combination with cisplatin. Moreover, flow cytometric analysis of lymphocyte surface markers of T cells (CD3+, CD4+ and CD8+), NK1.1 and B cells (CD19) indicated prominent enhancement in proliferation and differentiation of lymphocytes. T. cordifolia in combination with cisplatin selectively induced Th1 type of immune response as depicted by enhanced levels of IFN-γ and IL-2 whereas Th2 specific cytokines IL-4 and IL-10 observed a moderate decline. Confirmation of Th1 polarization was further obtained from augmented levels of IgG2a over IgG1 and heightened DTH (delayed type hypersensitivity) response. Thus, our results suggest that treatment by T. cordifolia may be a critical remedy for the amelioration of adverse effects of cisplatin. Thus, this might serve as a novel combination against visceral leishmaniasis in future.
Collapse
|
|
9
|
Aloia TA, Fahy BN. Chemotherapy-associated hepatotoxicity: how concerned should we be? Expert Rev Anticancer Ther 2010; 10:521-7. [PMID: 20397917 DOI: 10.1586/era.09.185] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Modern oncosurgical strategies are producing dramatic response rates and remarkable long-term survival rates for patients with hepatic colorectal cancer metastases. However, the increasing delivery of preoperative systemic chemotherapy to patients has coincided with recognition of possible chemotherapy-associated injury to the nontumoral liver. Although multiple groups have described gross changes in the appearance of the liver following systemic chemotherapy, the exact histopathologic lesions have not been clearly defined. A review of the literature on the topic indicates that host factors (e.g., diabetes mellitus and obesity) may be responsible for the development of liver injury as much as the drugs being delivered. With a lack of published evidence indicating that chemotherapy-associated liver injury results in adverse outcomes, several groups have recently questioned the clinical significance of this entity. This review describes the current understanding of this topic and seeks to answer the question of whether chemotherapy-associated liver injury actually impacts outcomes.
Collapse
Affiliation(s)
- Thomas A Aloia
- Department of Surgery, The Methodist Hospital Research Institute, 6550 Fannin Street, SM1661, Houston, TX 77030, USA.
| | | |
Collapse
|
|
10
|
Wang J, He D, Zhang Q, Han Y, Jin S, Qi F. Resveratrol Protects Against Cisplatin-Induced Cardiotoxicity by Alleviating Oxidative Damage. Cancer Biother Radiopharm 2009; 24:675-80. [PMID: 20025547 DOI: 10.1089/cbr.2009.0679] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Jingxuan Wang
- Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, China
| | - Dongning He
- Department of Medical Oncology, The 1st Affiliated Hospital of Jinzhou Medical College, Jinzhou, China
| | - Qingyuan Zhang
- Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, China
| | - Ying Han
- Department of Cardiology, The 1st Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shi Jin
- Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, China
| | - Feng Qi
- Department of Cardiac Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China
| |
Collapse
|
|
11
|
Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. ACTA ACUST UNITED AC 2008; 61:223-42. [PMID: 18986801 DOI: 10.1016/j.etp.2008.09.003] [Citation(s) in RCA: 360] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2008] [Revised: 09/04/2008] [Accepted: 09/10/2008] [Indexed: 02/07/2023]
Abstract
cis-Diamminedichloroplatinum (II) (cisplatin) is an important chemotherapeutic agent useful in the treatment of several cancers; however, it has several side effects such as nephrotoxicity. The role of the oxidative and nitrosative stress in cisplatin-induced nephrotoxicity is additionally supported by the protective effect of several free radical scavengers and antioxidants. Furthermore, in in vitro experiments, antioxidants or reactive oxygen species (ROS) scavengers have a cytoprotective effect on cells exposed to cisplatin. Recently, the participation of nitrosative stress has been more explored in cisplatin-induced renal damage. The use of a water-soluble Fe(III) porphyrin complex able to metabolize peroxynitrite (ONOO(-)) has demonstrated that this anion contributes to both in vivo and in vitro cisplatin-induced toxicity. ONOO(-) is produced when nitric oxide (NO*) reacts with superoxide anion (O(2)(*-)); currently, there are evidences suggesting alterations in NO* production after cisplatin treatment and the evidence appear to NO* has a toxic effect. This article goes through current evidence of the mechanism by more than a few compounds have beneficial effects on cisplatin-induced nephrotoxicity, contribute to understanding the role of oxidative and nitrosative stress and suggest several points as part of the mechanism of cisplatin toxicity.
Collapse
Affiliation(s)
- Yolanda I Chirino
- Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Tlalpan, DF, Mexico.
| | | |
Collapse
|