Morin hydrate downregulates inflammation-mediated nitric oxide overproduction and potentiates antioxidant mechanism against anticancer drug doxorubicin oxidative hepatorenal toxicity in rats.

Objective: Doxorubicin (DOX) is a frontline antineoplastic drug that kills cancer cells through genotoxic mechanism; however, it induces organ toxicities. This study assayed whether morin hydrate (MOH) could abrogate DOX hepatorenal toxicity in rats. Materials and Methods: There were 4 groups of rats: Control, MOH, DOX and MOH + DOX. Rats were administered MOH (orally, 100 mg/kg bw) for 7 consecutive days, while DOX was injected (40 mg/kg, ip) on the 5th day only. Hepatorenal function markers, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were estimated in both organs. Hepatorenal glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels were estimated with histopathology. Results: DOX significantly (p<0.05) reduced antioxidant enzyme activities and GSH level, while NO and MDA levels increased (p<0.05) compared to the control. DOX prominently altered hepatorenal indices and induced histopathological alterations. MOH abrogated the DOX hepatorenal toxicity and alleviated the histological lesions in the liver and kidney. Conclusion: MOH restored the indices via antioxidant mechanism and downregulation of NO overproduction in rats.

Ginger juice prevents cisplatin-induced oxidative stress, endocrine imbalance and NO/iNOS/NF-κB signalling via modulating testicular redox-inflammatory mechanism in rats.

The off-target testicular toxicity of the anticancer drug, cisplatin, is a current clinical concern and worrisome to male cancer patients. Growing evidence has implicated oxidative stress and inflammation in cisplatin toxicity. We have explored whether fresh ginger juice could mitigate testicular toxicity induced by anticancer drug cisplatin in rats. Rats were subjected to oral administration of fresh ginger juice (5 ml/kg body weight/day) for 5 days against testicular damage induced by single ip injection of cisplatin (CIS) (10 mg/kg body weight) on day 2 only. Testicular activities of antioxidant enzymes, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), inflammatory cytokines, inducible nitric oxide synthase (iNOS) and nuclear factor-ĸB (NF-ĸB) and serum hormone levels were estimated. CIS-induced prominent decreases in antioxidant enzyme activities, GSH and serum hormone levels, whereas levels of MDA, cytokines, NO, iNOS and NF-ĸB increased remarkably (p < .05) compared to control. Interestingly, the CIS-induced testicular alterations were considerably mitigated by the fresh ginger juice via abrogation of oxidative stress and anti-inflammatory mechanism. The study suggests, for the first time, antioxidant and anti-inflammatory effects of ginger juice against CIS testicular damage. Fresh ginger juice may have beneficial health impact on testicular side effect of CIS chemotherapy.

Nephroprotective activity of virgin coconut oil on diclofenac-induced oxidative nephrotoxicity is associated with antioxidant and anti-inflammatory effects in rats.

OBJECTIVE: Diclofenac is a non-steroidal anti-inflammatory drug linked with considerable organ toxicity caused via increased generation of reactive oxygen species. We evaluated whether the antioxidant effect of virgin coconut oil (VCO) could prevent diclofenac-induced oxidative nephrotoxicity in rats. MATERIALS AND METHODS: Randomized rats were pre-supplemented orally with VCO (5 or 10 ml/kg body weight) from day 1 to 24, and injected with normal saline or diclofenac (100 mg/kg) from day 22 to day 24 intraperitoneally. RESULTS: Diclofenac significantly (p<0.05) increased serum urea and creatinine levels. Renal tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels markedly (p<0.05) increased, whereas renal glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activities considerably (p<0.05) decreased compared to normal control. Histopathological alterations were caused by diclofenac. However, treatment with oral VCO for 21 days prior to diclofenac administration, attenuated histological renal damage, and restored antioxidant enzyme activities and TNF-α levels in kidney. CONCLUSION: These findings revealed that VCO has potential benefits to prevent diclofenac-induced nephrotoxic damage.

Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats.

Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity - a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1ß, (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liver function markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na+), potassium (K+), chloride (Cl-), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats.

BACKGROUND: Methotrexate (MTX) is an efficacious anticancer agent constrained in clinical use due to its toxicity on non-targeted tissue, a considerable source of worry to clinicians. Because the toxicity is associated with oxidative stress and inflammation, the study explored antioxidant and anti-inflammatory effect of virgin coconut oil (VCO) supplementation in nephrotoxicity induced by MTX in rats. METHODS: Rats were randomized into 4 groups (n=6) as follows: Control group; MTX group injected with single dose of MTX (20mg/kg, ip) on day 14; VCO (5%)+MTX and VCO (15%)+MTX groups were pre-treated with VCO diet and injected with single dose of MTX (20mg/kg, ip) on day 14. After 3 days of MTX injection, serum kidney markers, renal activities of antioxidant enzymes and glutathione (GSH) content were determined. Lipid peroxidation level and inflammatory markers- interleukin-6 (IL-6), nitric oxide (NO) and C-reactive protein (CRP) were estimated in kidney. Histopathological alterations were examined for kidney damage. RESULTS: MTX nephrotoxicity was evidenced by markedly elevated serum renal markers along with significant decreases in renal GSH and activities of antioxidant enzymes confirmed by histopathology. Lipid peroxidation level, IL-6, NO and CRP markedly increased compared to control. VCO supplementation prior to MTX injection attenuated MTX-induced oxidative nephrotoxicity via prominent increases in GSH and antioxidant enzyme activities in a dose-dependent manner. The renal inflammatory markers and MDA depleted considerably compared to MTX control group. Histopathological alterations were mitigated to confirm the biochemical indices. CONCLUSION: VCO supplementation demonstrates nephroprotective activity by attenuating MTX oxidative nephrotoxicity via antioxidant and anti-inflammatory activities in kidney. Our results suggested that VCO may benefit cancer patients on MTX chemotherapy against kidney injury.