Gentamicin (GM) is a broad-spectrum antibiotic widely used for severe bacterial infections, but itis associated with acute nephrotoxicity. Ambrosia maritima L. is an annual herbaceous plant that has avariety of medicinal and antioxidant activities. Vitamin D3 is involved in a multitude of biological functions and essential antioxidant pathways. This study aims to investigate the protective effects of Damsissa (Ambrosia maritima) versus vitamin D3 against GM-induced nephrotoxicity using 72 male rats that were randomly divided into six groups: control, Damsissa (100 mg/kg/day), vitamin D3 (1000 IU/kg/day), GM(100 mg/kg/day for 7 days), GM + Damsissa, and GM + vitamin D3. Renal function, oxidative stress biomarkers (MDA, CAT, SOD, GSH), cytokine levels (IL-1β, IL-6, TNF-α, IL-4), and gene expression (Caspase-3, Keap1, PPARγ, Nrf2) were assessed. Histopathological and ultrastructural kidney analyses were conducted using H&E, Masson's trichrome, PCNA staining, and transmission electron microscopy. Blood samples were tested for renal and liver markers (creatinine, BUN, AST, ALT). Damsissa enhanced survival rates, returned the renal indices to near normal, and ameliorated pathological changes based on immunohistopathological and ultrastructural results. They further reduced pro-inflammatory cytokine production, optimized oxidative stress markers, and normalized gene expression levels. Both treatments exhibited abundant antioxidant and anti-inflammatory effects, which remarkably reduced GM-induced acute kidney injury. These results suggest that both Damsissa and vitamin D3 may exert protective effects against drug-induced nephrotoxicity.

Combination treatment enhances the therapeutic potential for diabetes, particularly for patients with severe complications. Combining standard therapeutic drugs with alternative bioactive compounds provides a promising option for long-term treatment, given the high safety profile of bioactive substances. Objective in this study, we aimed to evaluate the synergistic effects of metformin and Clinacanthus nutans (Burm. f.) Lindau (CN) on glucose metabolism and renal dysfunction parameters in a type 2 diabetic rat model.

Male Wistar rats were fed a high-fat diet for 4 weeks and then received a low dose of streptozotocin to induce type 2 diabetes. The diabetic rats were randomly divided into four groups: untreated diabetic rats (DM), diabetic rats treated with CN at doses of 100 or 200 mg/kg/day (DM100 or DM200), diabetic rats treated with a combination of CN and metformin (DMCOM), and diabetic rats treated with metformin at 100 mg/kg/day (DMMET). The treatments were administered by gavage for 4 weeks.

Compared to single treatments, DMCOM showed a remarkable effect in reducing several parameters, including serum creatinine and blood urea nitrogen, while enhancing creatinine clearance in diabetic rats. Additionally, DMCOM significantly decreased malondialdehyde levels. Notably, diabetic rats treated with DMCOM exhibited a significant reduction in parameters associated with renal dysfunction, as evidenced by decreased inflammation markers, along with downregulated fibrotic markers.

Our findings provide a scientific basis for the clinical application of CN and suggest a new strategy for preventing nephrotoxicity and other kidney diseases in diabetic patients.

The well-known antibiotic gentamicin (GEN) works well against a variety of pathogenic bacteria, nevertheless its therapeutic use might be limited by the possibility of nephrotoxicity. The naturally occurring flavonoid galangin (GAL) has several interesting anti-inflammatory and antioxidant properties. The present study evaluated the nephroprotective effect of GAL on GEN-induced renal injury. Rats received GAL for 14 days and GEN from day 8 to day 14. There was a significant increase in serum urea and creatinine along with several histopathological changes in the kidney following GEN administration. GEN-treated rats also showed increased levels of kidney MDA and NO, and decreased GSH content and activities of antioxidant enzymes. Rats received GEN also demonstrated increased NF-κB p65, iNOS, TNF-α, IL-1β and IL-6 levels in the kidney. GAL remarkably prevented tissue injury, attenuated MDA and NO levels, improved antioxidants, and decreased levels of inflammatory mediators in the kidney of GEN-treated rats. Furthermore, GEN-administrated rats exhibited increased Bax and caspase-3 with concomitant decline in Bcl-2 levels in the kidney, an effect that GAL attenuated. In conclusion, GAL prevents GEN-induced nephrotoxicity by attenuating oxidative stress, inflammation, and apoptosis and augmenting antioxidant defense, suggesting its therapeutic potential against drug nephrotoxicity.

Diabetic retinopathy (DR) is one of the major eye diseases contributing to blindness worldwide. Endoplasmic reticulum (ER) stress in retinal cells is a key factor leading to retinal inflammation and vascular leakage in DR, but its mechanism is still unclear.

To investigate the potential mechanism of LEF1 and related RNAs in DR.

ARPE-19 cells were exposed to high levels of glucose for 24 hours to simulate a diabetic environment. Intraperitoneally injected streptozotocin was used to induce the rat model of DR. The expression levels of genes and related proteins were measured by RT-qPCR and Western blotting; lnc-MGC and miR-495-3p were detected by fluorescent in situ hybridization; CCK-8 and TUNEL assays were used to detect cell viability and apoptosis; enzyme-linked immunosorbent assay was used to detect inflammatory factors; dual-luciferase gene assays were used to verify the targeting relationship; and the retina was observed by HE staining.

LEF1 and lnc-MGC have binding sites, and lnc-MGC can regulate the miR-495-3p/GRP78 molecular axis. In high glucose-treated cells, inflammation was aggravated, the intracellular reactive oxygen species concentration was increased, cell viability was reduced, apoptosis was increased, the ER response was intensified, and ferroptosis was increased. As an ER molecular chaperone, GRP78 regulates the ER and ferroptosis under the targeting of miR-495-3p, whereas inhibiting LEF1 can further downregulate the expression of lnc-MGC, increase the level of miR-495-3p, and sequentially regulate the level of GRP78 to alleviate the occurrence and development of DR. Animal experiments indicated that the knockdown of LEF1 can affect the lnc-MGC/miR-495-3p/GRP78 signaling axis to restrain the progression of DR.

LEF1 knockdown can regulate the miR-495-3p/GRP78 molecular axis through lnc-MGC, which affects ER stress and restrains the progression of DR and ferroptosis in retinal pigment epithelial cells.

Biopolymeric drug delivery systems enhance the bioavailability and therapeutic efficacy of poorly soluble bioactive compounds. In this study, chitosan (Chi), dextran (Dex), carboxymethyl dextran (mDex), lignin (L), and curcumin (Cu) were combined to develop materials with controlled release, antioxidant, and anti-inflammatory properties. The mechanical evaluation showed that Chi-mDex-L-Cu exhibited the highest diametral tensile strength (2.40 MPa), a 1233% increase compared to Chi-mDex-L, due to strong hydrogen bonding interactions between curcumin and matrix components. Curcumin release kinetics, modeled using the Weibull equation, demonstrated that Chi-mDex-L-Cu presented the slowest release rate, reducing the cumulative release by 55.66% as compared to Chi-L-Cu, ensuring prolonged bioactivity. Despite its controlled release, Chi-mDex-L-Cu retained 60% antioxidant and 70% anti-inflammatory activity, making it a promising sustained-release system. The biocompatibility assessment confirmed cell viability above 85%, with Chi-mDex-L-Cu showing a slight (~10%) reduction at higher concentrations while remaining non-cytotoxic. These findings suggest that Chi-mDex-L-Cu is a strong candidate for biomedical applications requiring prolonged therapeutic effects, such as osteoarthritis treatment.

Gentamicin (Genta)-induced nephrotoxicity poses a significant clinical challenge due to its detrimental effects on kidney function. Clopidogrel (Clop), an antiplatelet drug known for its ability to prevent blood clots by inhibiting platelet aggregation, also has potential effects on oxidative stress and cell death. This study investigates Clop's protective role against Genta-induced nephrotoxicity, emphasizing the importance of the coagulation cascade. The 32 adult male albino rats were randomly assigned to four groups of eight (n = 8). The first group received only the vehicle. Genta was injected intraperitoneally at 100 mg/kg/day for 8 days in the second group. Groups 3 and 4 received oral Clop at 10 and 20 mg/kg/day for 1 week before Genta delivery and throughout the experiment. Renal tissue showed renal function tests, oxidative stress, pro-inflammatory cytokines, apoptotic markers, coagulation profile, and fibrin expression. Clop improved Genta-induced kidney function and histopathology. Clop substantially reduced pro-inflammatory cytokines, oxidative stress indicators, pro-apoptotic proteins, and fibrin protein. Clop also significantly boosted renal tissue anti-inflammatory and anti-apoptotic protein expression. Genta-induced nephrotoxicity involves oxidative stress, apoptosis, and coagulation system activation, according to studies. This study underscores that Genta-induced nephrotoxicity is associated with oxidative stress, apoptosis, and activation of the coagulation system. Clop's protective effects on nephrons are attributed to its anticoagulant, antioxidant, anti-inflammatory, and anti-apoptotic properties, presenting it as a promising therapeutic strategy against Genta-induced kidney damage.

Doxorubicin (DOXO) is a powerful anthracycline chemotherapeutic drug, but its clinical usage has been limited by its deleterious effects on different organs, particularly hepatotoxicity. The aim of this study was to establish the combined effects of aerobic interval training (AIT) and curcumin supplementation on mitigating oxidative damage and endoplasmic reticulum (ER) stress-mediated apoptosis in a rat model of DOXO-induced hepatotoxicity. Fifty-six male Sprague-Dawley rats were randomly split into six groups: control (CON), vehicle, doxorubicin (Dox), doxorubicin + curcumin (Dox-C), doxorubicin + AIT (Dox-A), and doxorubicin + curcumin + AIT (Dox-AC). DOXO was intraperitoneally injected weekly (4 mg/kg/week) for five weeks. Curcumin supplementation (100 mg/kg/day) and AIT (4 min at 80-90% of VO2max intermitted by 3 min of active rest at 65-75% of VO2max) were conducted five times a week for six weeks. Finally, the hepatic tissue and blood samples were collected to assess histopathological changes, liver damage biomarkers, and the protein expression of oxidative stress, ER stress, and apoptosis markers. Tissue sections revealed that AIT and curcumin supplementation significantly improved hepatotoxicity induced by DOXO, as evidenced by the positive effects on histopathological alterations and serum markers of hepatic damage (P < 0.05). Both curcumin and AIT significantly reduced DOXO-triggered oxidative damage, ER stress, and apoptosis (P < 0.05), with the latter showing slightly higher effectiveness. Consequently, the combination of AIT with curcumin supplementation exhibits protective effects against chronic hepatotoxicity induced by DOXO, with AIT demonstrating relatively greater efficacy in increasing antioxidant capacity and reducing ER stress and apoptosis.

Gentamicin (GM) is extensively used as an antibiotic for the treatment of infections caused by Gram-negative bacteria. Oxidative stress and proinflammatory cytokines are implicated in GM-induced renal damage. Chrysin (CH), also known as 5,7-dihydroxyflavone, has been used in traditional medicine to treat various kidney disorders. The aim of this study was to investigate the antioxidant, anti-apoptotic, and anti-inflammatory effects of CH against nephrotoxicity induced by GM.

Male rats were separated into four equal groups: a negative control group (NC), a CH-treated group (100 mg/kg/day per os), a group treated with GM (100 mg/kg/day IM), and a group treated with both GM and CH (100 mg/kg/day), for 10 days. Blood and urine renal markers were investigated.

GM caused increases in the serum creatinine and urea levels and decreases in creatinine clearance, urine flow, and urine volume in the GM-treated rats. Moreover, there were increases in the levels of IL-1β, TNF-α, IL-18, and MDA in the renal tissues, with an augmented expression of NF-κB/KIM-1, as well as decreases in antioxidant marker (GSH, GPx, CAT, and SOD) activities and decreased expressions of the anti-inflammatory transcription factors Nrf2 and AKT. The simultaneous treatment with CH in the GM-treated group protected renal tissues against the nephrotoxicity induced by GM, as demonstrated by the normalization of renal markers and improvement in histopathological damage.

This study reveals that CH may attenuate GM-induced renal toxicity in rats.

Ischemic stroke is a devastating neurovascular condition that occurs when cerebral tissue fails to receive an adequate supply of oxygen. Despite being a leading cause of death and disability worldwide, therapeutic interventions are currently limited. Polyamidoamine (PAMAM) dendrimers are nanomolecules commonly used in biomedical applications due to their ability to encapsulate small-molecules and improve their pharmacokinetic properties. Curcumin is known to have anti-inflammatory and antioxidant effects yet suffers from poor solubility and bioavailability. The purpose of this study is to investigate the efficacy of curcumin encapsulated in PAMAM dendrimers as a potential therapeutic treatment for ischemic stroke by studying post-stroke lesion size, astrocyte reactivity, and functional recovery in a rat model of cerebral ischemia.

Forty-eight male and female Sprague-Dawley rats (280-380 g) underwent either a 90-min middle cerebral artery occlusion (MCAo) or sham surgery before receiving one of four treatments: (1) Hanks' balanced salt solution (HBSS) control, (2) empty dendrimer control, (3) curcumin control, or (4) curcumin encapsulated in PAMAM dendrimer. Neurobehavioral outcomes were evaluated at 1-, 3-, 5-, and 7-day post-surgery, after which animals were euthanized on day 8 to assess infarct volume and GFAP immunoreactivity.

Animals that received formulations containing dendrimers (curcumin encapsulated in dendrimers or empty dendrimers) demonstrated significantly lower levels of GFAP immunoreactivity and improved functional recovery, including weight and neurobehavioral scores, compared to the formulations that did not contain dendrimers (curcumin and HBSS control). Additionally, the dendrimer-curcumin treatment group exhibited a significantly improved paw laterality index over the course of the study compared with the other three treatment groups.

Although the post-stroke administration of curcumin encapsulated in PAMAM dendrimers modulates the astrocytic response and promotes functional recovery following ischemic stroke in rats, its therapeutic benefits may be driven by PAMAM dendrimers as the empty dendrimer treatment group also showed significant improvements post-stroke. Further investigation regarding PAMAM dendrimers in treating neuroinflammatory conditions remains warranted.

Gut microbiota is a complex and dynamic system that plays critical roles in human health and various disease. Progressive chronic kidney disease (CKD) suggests that patients irreversibly progress to end-stage kidney disease and need renal replacement treatments, including dialysis and transplantation. Ample evidence indicates that local oxidative stress and inflammation play pivotal roles in the pathogenesis and progression of CKD and dysbiosis of gut microbiota. CKD is always accompanied by intestinal inflammation and oxidative stress, which lead to rapid systemic translocation of bacterial-derived uraemic toxins, including indoxyl sulphate, phenyl sulphate and indole-3-acetic acid, and the consequent development and aggravation of renal fibrosis. Although inflammation and oxidative stress have been extensively discussed, there is a paucity of reports on the effects of gut microbiota on renal fibrosis and gut microbiota mediation of oxidative stress and inflammation. This review provides an overview of gut microbiota on inflammation and oxidative stress in renal fibrosis, briefly discusses regulation of the gut flora using microecological preparations and natural products, such as resveratrol, curcumin and emodin as treatments for CKD, and provides a clear pathophysiological rationale for the design of promising therapeutic strategies.

Gentamicin-induced nephrotoxicity primarily results from renal inflammatory cascades and increased oxidative stress. This study aims to examine the effects of hydrogen-rich water (HRW) on gentamicin-induced renal damage in rats. Thirty-two rats were equally divided into four groups, including control (no treatment), hydrogen, gentamicin, and gentamicin+hydrogen. At the end of one week, all animals were euthanized following ethical rules, and blood and tissue samples were analyzed for examining Malondialdehyde (MDA), glutathione (GSH), Tumor Necrosis Factor-Alfa (TNF-α), Tumor Necrosis Factor-Beta (TNF-β), Interleukin 6 (IL-6), endoglin, endocan, urea, creatinine, Na+, and K+ parameters. Levels of 8-Hydroxyguanosine (8-OHdG), MDA, and Bax were immunohistochemically analyzed. Data showed that while MDA (control P<0.0001, H2P<0.0001, ‎Genta+H2P<0.0007), TNF-α (control P<0.0002, H2P<0.0040, ‎Genta+H2P<0.0381), IL-6 (control P<0.0044, H2P<0.0070, ‎Genta+H2P<0.0109), endocan (control P<0.0460, H2P<0.0286, ‎Genta+H2P<0.0452), and endoglin (control P<0.0131, H2P<0.0164, ‎Genta+H2P<0.0397), urea (control P<0.0024, H2P<0.0001, ‎Genta+H2P<0.0180), and creatinine parameters (control P<0.0017, H2P<0.0178, ‎Genta+H2P<0.0011) increased in the gentamicin group compared to the other groups, a decrease in these parameters was observed in the gentamicin+hydrogen group compared to the gentamicin group. The Genta group had greater levels of TNF-β than the control (P<0.0042) and H2 groups (P<0.0268). GSH content was higher in the hydrogen group compared to the gentamicin group. Immunohistochemically, 8-OHdG, MDA, and Bax expressions increased in the gentamicin group compared to the control group, whereas they decreased in the gentamicin+hydrogen group compared to the gentamicin group. Hydrogen may be an alternative treatment for oxidative stress-induced nephrotoxicity.

Spinal cord injury (SCI) is damage to the spinal cord that permanently or temporarily disrupts its function, causing considerable autonomic, sensory, and motor disorders, and involves between 10 and 83 cases per million yearly. Traumatic SCI happens following primary acute mechanical damage, leading to injury to the spinal cord tissue and worsening clinical outcomes. The present therapeutic strategies for this complex disease fundamentally rely on surgical approaches and conservative remedies. However, these modalities are not effective enough for neurological recovery. Therefore, it is necessary to discover more efficient methods to treat patients with SCI. Today, considerable attention has been drawn to bioactive compounds-based remedies and stem cell therapy for curing various ailments and disorders, such as neurological diseases. Some researchers have recommended that harnessing curcumin, a polyphenol obtained from turmeric, in combination with stem cells, like mesenchymal stem cells, neural stem cells, and ependymal stem cells, can remarkably improve neurological recovery-related parameters more effective than the treatment with these two methods separately in experimental models. Hereby, this literature review delves into the functionality of curcumin combined with stem cells in treating SCI with a focus on cellular and molecular mechanisms.

The use of gentamicin (GNT) is associated with acute kidney injury (AKI). Ferroptosis is a newly recognized iron-dependent, non-apoptotic cell death that can lead to AKI. Lactoferrin (LF), an iron-binding glycoprotein, was previously reported to be renoprotective. Nonetheless, LF's impact on GNT-induced AKI and ferroptosis has not yet been investigated. Accordingly, we assessed the dose-dependent effect of LF on GNT-induced AKI and its influence on ferroptosis. Thirty-six male rats were allocated as control, LF, GNT (100 mg/kg/day, i.p.), and groups given LF (100, 200, and 300 mg/kg, p.o.) for 14 days prior concurrently with GNT (Day 8-14). The high dose of LF (300 mg/kg) showed better histopathological picture, higher creatinine clearance, reduced serum and urine levels of kidney injury markers when compared to the GNT group and the lower two doses. These nephroprotective effects of LF can be attributed to the observed reduction in renal ferrous iron, 4-HNE, and MDA, miR-378a-3p and ALOX15 expression, TFR1, NCOA4, and ACSL4 protein expression and the increased LINC00618 expression, GSH levels, GPX4, SLC7A11, and FSP1 protein expression. In conclusion, LF high dose was the most renoprotective against GNT-induced AKI, in which suppression of ferroptosis pathways was a likely contributor to its protective mechanism.

The increased rate of antibiotic resistance strongly limits the resolution of Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. Therefore, new strategies to control bacterial infections are urgently needed. Bacillus subtilis (B. subtilis) and its metabolites are desirable antibacterial agents. Here, we aimed to evaluate the antibacterial activity of the novel B. subtilis strain GXYX (No: PRJNA940956) crude lipopeptide against S. Typhimurium. In vitro, GXYX crude lipopeptides affected S. Typhimurium biofilm formation and swimming and attenuated the adhesion and invasion abilities of S. Typhimurium toward BHK-21 cells; in addition, it inhibited the mRNA expression of the filA, filC, csgA, and csgB genes, which are related to the adhesion and invasion ability of S. Typhimurium. In vivo, pretreatment with GXYX crude lipopeptide via intragastric administration improved the survival rate by 30%, which was related to reductions in organ bacterial loads and clinical signs in mice. Intragastric administration of GXYX crude lipopeptide significantly downregulated the mRNA levels of TNF-α, IL-1β, IL-12 and IL-6 in response to S. Typhimurium-induced inflammation compared with intraperitoneal injection. Moreover, it significantly improved the intestinal barrier-related gene (ZO-1, claudin-1, occludin-1) mRNA levels in intestinal tissue damaged by S. Typhimurium infection. In conclusion, GXYX crude lipopeptides were effective at reducing S. Typhimurium colonization, laying a foundation for the further development of novel antibacterial agents.

Acute kidney injury (AKI) is a global health problem, given its substantial morbidity and mortality rates. A better understanding of the mechanisms and factors contributing to AKI has the potential to guide interventions aimed at mitigating the risk of AKI and its subsequent unfavorable outcomes. Endoplasmic reticulum stress (ERS) is an intrinsic protective mechanism against external stressors. ERS occurs when the endoplasmic reticulum (ER) cannot deal with accumulated misfolded proteins completely. Excess ERS can eventually cause pathological reactions, triggering various programmed cell death (autophagy, ferroptosis, apoptosis, pyroptosis). This article provides an overview of the latest research progress in deciphering the interaction between ERS and different programmed cell death. Additionally, the report consolidates insights into the roles of ERS in AKI and highlights the potential avenues for targeting ERS as a treatment direction toward for AKI.

Gentamicin (GEN) is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Our study aimed to explore curcumin's (CMN) protective role against GEN-induced renal and cardiac toxicity. Rats were randomly classified into 4 equal groups; Control (cont), GEN (100 mg/kg b.wt, i.p.) for seven days, CMN (200 mg/kg b.wt, orally) for 21 days, and CMN + GEN groups. GEN caused renal and cardiac dysfunctions; increased urea, creatinine, uric acid, cystatin C, CK-MB, LDH, and troponin I serum levels. MDA level was elevated significantly while activities of SOD, CAT, and GSH level were reduced significantly in renal and cardiac tissues. GEN-intoxicated rats showed up-regulation of NF-κB, IL-1β, Keap1, HMOX1, and BAX with down-regulation of Nrf2, and Bcl-2 mRNA expression in renal and cardiac tissues. Also, GEN-induced up-regulation of renal mRNA expression of KIM-1, NGAL, and intermediate filament proteins [desmin, nestin, and vimentin] as well cardiac gene expression of cMyBP-C and H-FABP. GEN-induced toxicity was significantly attenuated by CMN co-treatment as CMN improved renal and cardiac biomarkers, reduced oxidative stress and inflammatory response, and reversed alterations in mRNA expression of all tested renal and cardiac genes. These outcomes indicated that CMN could protect renal and cardiac tissues against GEN-induced oxidative stress, inflammation, and apoptosis.

Background: Nephrotoxicity refers to the toxigenic impact of compounds and medications on kidney function. There are a variety of drug formulations, and some medicines that may affect renal function in multiple ways via nephrotoxins production. Nephrotoxins are substances that are harmful to the kidneys. Purpose: This investigation examines the renoprotective effect of gymnemic acid (GA) on Wistar rats in gentamicin-induced nephrotoxicity by analyzing serum, kidney, and histopathological markers. Study-design/methods: The current study investigated the protective effect of GA at doses of 20, 40, and 60 mg/kg against gentamicin-induced nephrotoxicity in rats. Vitamin E was administered to compare the antioxidant capacity and efficacy of GA. In addition to the treatment groups, 100 mg/kg of gentamicin was administered intraperitoneal for 14 days. At the end of the study protocol, kidney homogenate, blood, and serum were evaluated biochemically. Serum creatinine, blood urea, glomerular filtration rate (GFR), mitochondrial dysfunctions, inflammatory cytokines, and renal oxidative stress were examined to assess gentamicin-induced nephrotoxicity. In addition, the impact of GA on the above-mentioned nephrotoxic markers were evaluated and further confirmed by histological analysis. Results: This study establishes a correlation between antibiotic use, especifically aminoglycosides and acute renal failure. The research demonstrates the nephrotoxic effects of aminoglycosides, inducing mitochondrial ETC-complex dysfunction, and renal tissue inflammation in experimental rats. GA's antioxidant properties restored renal oxidative stress markers, reducing kidney inflammation and injury. Histopathological analysis revealed a significant reduction in renal injury with GA treatment. Additionally, GA demonstrated greater efficacy than Vitamin E in restoring antioxidant potential and mitochondrial enzymes. Conclusion: Consequently, our findings imply that long-term use of GA may be a suitable therapeutic strategy for reducing aminoglycoside toxicity. The current study suggests GA's potential in treating gentamicin-induced nephrotoxicity and acute renal failure, meriting further investigation using advanced techniques.

It has been for thousands of years in China known medicinal homologous foods that can be employed both as foods and medicines to benefit human and animal health. These edible herbal materials perform divert roles in the regulation of metabolic disorders, cancers, and immune-related diseases. Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. However, the potential mechanisms of curcumin-derived modulation still need to be developed and attract more attention worldwide. Given that these signal pathways are enrolled in important bioactive reactions, we collected curcumin's last achievements predominantly on the immune-regulation signals with the underlying targetable strategies in the last 10 years. This mini-review will be helpful to accelerate curcumin and other extracts from medicinal homologous foods use in future human clinical applications.

Fipronil is a phenylpyrazole insecticide that is widely used in agricultural, veterinary, and public health fields for controlling a wide variety of insect species and it is an environmentally potent toxic substance. Curcumin and quercetin, which are well-known natural antioxidants, are widely used to prevent the harmful effects of free radicals on biological systems. The present study aimed to determine the potential ameliorative effects of quercetin and/or curcumin on fipronil-induced nephrotoxicity in rats. Curcumin (100 mg/kg of body weight), quercetin (50 mg/kg of body weight), and fipronil (3.88 mg/kg of body weight) were administered to male rats by intragastric gavage for 28 consecutive days. In the present study, body weight, kidney weight, the renal function markers (blood urea nitrogen, creatinine, and uric acid levels) in the blood, antioxidant enzyme activities, and malondialdehyde level as markers of oxidative stress, and histological changes of the renal tissue were evaluated. The levels of serum blood urea nitrogen, creatinine, and uric acid were significantly increased in fipronil-treated animals. Additionally, while superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase activities were decreased in the kidney tissue of rats treated with fipronil, malondialdehyde level was significantly increased. Histopathological analyses showed that the glomerular and tubular injury occurred in the renal tissue of fipronil-treated animals. Also, the supplementation of quercetin and/or curcumin with fipronil significantly improved fipronil-induced alterations in renal function markers, antioxidant enzyme activities, malondialdehyde levels, and histological features of renal tissue.

The current experiment aimed to identify the possible protective role of rivastigmine (RIVA) in gentamicin (GNT)-induced acute kidney injury (AKI) in rats. RIVA was administered in the presence and absence of GNT. Kidney function markers and serum and renal GNT concentrations were measured. Renal oxidative stress parameters as well as inflammatory and apoptotic biomarkers were evaluated. Renal histopathological assessment and nuclear factor kappa-B (NF-κB) immunohistochemical study were performed. GNT administration increased serum creatinine, urea, and cystatin C concentrations. RIVA ameliorated these changes via mitigating GNT-induced increases of renal oxidative stress, inflammation, and apoptotic parameters. RIVA showed a prompt improvement in the histopathological renal damage and a decrease in NF-κB immunoexpression. In conclusion, RIVA protective effects against GNT-induced AKI are mediated by decreasing GNT concentration in renal tissue and other effects like antioxidant and antiapoptotic effects possibly through its cholinergic anti-inflammatory action.

Gentamicin remains widely used in all age groups despite its well-documented nephrotoxicity; however, no adjuvant therapies have been established to counteract this side effect. Our study aimed to experimentally determine whether curcumin and vitamin C have nephroprotective effects and whether certain reactive species could be used as markers of early gentamicin nephrotoxicity. Wistar adult male rats were evenly distributed into four groups: control, gentamicin, curcumin and gentamicin, vitamin C and gentamicin (gentamicin: 60 mg/kg/day, intraperitoneally, 7 days). We determined renal function (urea, creatinine), oxidative stress (malondialdehyde, nitric oxide, 3-nitrotyrosine, total oxidative stress), and antioxidant and anti-inflammatory status (thiols, total antioxidant capacity, interleukin-10). Nephrotoxicity was successfully induced, as shown by the elevated creatinine levels in the gentamicin group. In contrast, supplementation with curcumin and vitamin C prevented an increase in urea levels while decreasing total oxidative stress levels compared to the gentamicin group. Moreover, vitamin C and curcumin distinctively modulate the levels of nitric oxide and malondialdehyde. Histological analysis showed more discrete lesions in rats that received vitamin C compared to the curcumin group.

This study aimed to establish the relationship between two endoplasmic reticulum (ER) stress proteins, glucose-regulated protein 78 (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK), and oxidative stress markers in cisplatin (CIS)-induced and gentamicin (GEN)-induced nephrotoxicity.The study consisted of five groups: control (saline solution only), CIS D2 (2.5 mg/kg for 2 days), CIS D7 (2.5 mg/kg for 7 days), GEN D2 (160 mg/kg for 2 days), and GEN D7 (160 mg/kg for 7 days). All rats were sacrificed 24 h after the last injection for standard clinical chemistry, and ultrastructural and histological evaluation of the kidney.CIS and GEN increased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as total oxidant status (TOS), while decreasing total antioxidant status (TAS) level in CIS D7 and GEN D7 groups. Histopathological and ultrastructural findings were also consistent with renal tubular damage. In addition, expression of markers of renal inflammation (tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β)) and ER stress markers (GRP78 and PERK) was significantly increased in the kidney tissue of rats treated with CIS and GEN for 7 days.These findings suggest that CIS and GEN administration for 7 days aggravates nephrotoxicity through the enhancement of oxidative stress, inflammation, and ER stress-related markers. As a result, the recommended course of action is to utilize CIS and GEN as an immediate but brief induction therapy, stopping after 3 days and switching to other drugs instead.

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Gentamycin-induced nephrotoxicity is related to stimulation of oxidative stress and inflammatory cascades leading to apoptotic renal damage. Heme oxygenase-1 (HO-1) induction considered to be an adaptive response against oxidative tissue damage. Our study aimed to investigate the possible nephroprotective role of HO-1 inducers (hemin and erythropoietin (EPO)) and elucidate their potential underlying molecular mechanisms by assessing their antioxidant, anti-apoptotic, and anti-inflammatory properties.

Kidney function markers (urea and creatinine), lipid peroxidation and antioxidant markers (MDA and GPx), inflammation and apoptotic markers (IL-6 and Bcl-2), and the relative gene expression levels of Nrf2 and HO-1 were assessed. Histopathological changes of the kidney were examined.

Nephrotoxic rats pretreated with hemin showed significant decrease in serum level of urea, creatinine, and MDA, compared to non-treated group. The kidney tissues also showed significant elevation of Bcl2 level, but significant decrease of IL-6, compared to non-treated group. Moreover, hemin pre-treatment significantly upregulated gene expression of Nrf2 and HO-1 in kidney tissue to near the normal control group. On the other hand, pretreatment with EPO showed significant upregulation of HO-1 gene expression but didn't show significant difference in Nrf2 gene expression compared to control group. The histopathological examination of kidney supported the biochemical results.

The current results proved that hemin rather than EPO, showed reno-protective effects in rats, which was mediated by activation of Nrf2 signaling pathway. This could be also attributed to the observed anti-inflammatory, antioxidant, and anti-apoptotic properties of hemin. In this regard, EPO showed lower potency.

Drug-induced acute kidney injury (AKI), especially from exposure to antibiotics, has a high prevalence secondary to their frequent prescription. Typically, drug-induced AKI results from acute tubular necrosis or acute interstitial nephritis. While some risk factors for the development of AKI in individuals treated with antibiotics are modifiable, others such as concomitant drug therapies to treat comorbidities, age, and pre-existing chronic kidney disease are not modifiable. As such, there is an urgent need to identify strategies to reduce the risk of AKI in individuals requiring antibiotic therapy. Natural products, especially those rich in active constituents possessing antioxidant properties are an attractive option to mitigate AKI risk. Given that mitochondrial dysfunction precedes AKI and natural products can restore mitochondrial health and counter the oxidative stress secondary to mitochondrial damage investigating their utility warrants further attention. The following review summarizes the available preclinical and clinical evidence that provides a foundation for future study.

Primary and secondary immunodeficiencies cause an alteration in the immune response which can increase the rate of infectious diseases and worsened prognoses. They can also alter the immune response, thus, making the infection even worse. Curcumin is the most biologically active component of the turmeric root and appears to be an antimicrobial agent. Curcumin cooperates with various cells such as macrophages, dendritic cells, B, T, and natural killer cells to modify the body's defence capacity. Curcumin also inhibits inflammatory responses by suppressing different metabolic pathways, reduces the production of inflammatory cytokines, and increases the expression of anti-inflammatory cytokines. Curcumin may also affect oxidative stress and the non-coding genetic material. This review analyses the relationships between immunodeficiency and the onset of infectious diseases and discusses the effects of curcumin and its derivatives on the immune response. In addition, we analyse some of the preclinical and clinical studies that support its possible use in prophylaxis or in the treatment of infectious diseases. Lastly, we examine how nanotechnologies can enhance the clinical use of curcumin.

Lead (Pb) has many applications in daily life, but in recent years, various problems caused by lead exposure have aroused people's concern. Folic acid is widely found in fruits and has received more attention for its antioxidant function. However, the role of folic acid in lead-induced kidney injury in rats is unclear. This study was designed to investigate the effects of folic acid on oxidative stress and endoplasmic reticulum stress in the kidney of rats caused by lead exposure.

Forty specific pathogen-free male Rattus norvegicus rats were randomly divided into control, lead, intervention, and folic acid groups. The levels of SOD, GSH-Px, GSH, and MDA were measured by biochemical kits. The protein levels of Nrf2, HO-1, CHOP, and GRP78 were measured by immunofluorescence.

This study showed that lead exposure increased the blood levels of lead in mice. However, the intervention of folic acid decreased the levels of lead, but the difference was not statistically significant. Lead exposure causes oxidative stress by decreasing kidney SOD, GSH-Px, and GSH levels and increasing MDA levels. However, folic acid alleviated the oxidative damage caused by lead exposure by increasing the levels of GSH-Px and GSH and decreasing the levels of MDA. Immunofluorescence results showed that folic acid intervention downregulated the upregulation of kidney Nrf2, HO-1, GRP78, and CHOP expression caused by lead exposure.

Overall, folic acid alleviates kidney oxidative stress induced by lead exposure by regulating Nrf2 and HO-1, while regulating CHOP and GRP78 to mitigate apoptosis caused by excessive endoplasmic reticulum stress.