Hepatoprotective effect of polyphenols isolated from virgin coconut oil against sub-chronic cadmium hepatotoxicity in rats is associated with improvement in antioxidant defense system.

Cadmium (Cd) is a ubiquitous non-essential environmental and industrial toxicant that affects various organs in humans and experimental animals. Robust evidence confirms the contribution of oxidative stress to the pathogenesis of Cd-induced hepatic damage. Potent polyphenols found in virgin coconut oil (VCO) are free radical scavengers that may be beneficial against Cd hepatotoxicity. Thus, we aimed to evaluate the possible protective effect of polyphenols isolated from VCO on Cd-induced hepatotoxicity and oxidative stress in rats. Rats were pretreated with polyphenols isolated from VCO (10, 20, and 50 mg/kg, orally) 2 weeks prior to concurrent Cd administration (5 mg/kg, orally) for 5 weeks. Subsequently, liver damage, hepatic oxidative stress, and histopathological alterations were evaluated. In vitro antioxidant assays (DPPH and FRAP) were carried out on VCO polyphenols. Cadmium induced liver damage demonstrated by significant alterations in serum markers of liver damage, as well as pronounced decrease in albumin and total protein compared to control. Further, Cd remarkably depressed hepatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) content. Hepatic lipid peroxidation was markedly increased as highlighted by malondialdehyde (MDA) content. Sub-chronic administration of VCO polyphenols to Cd-treated rats produced a significant hepatoprotective effect and restored hepatic oxidative stress markers comparable to control. The prominent improvement in histopathology of rat liver confirmed the biochemical findings. The findings suggest potential beneficial effect of VCO polyphenols on Cd-induced hepatotoxicity and oxidative stress in rats; the mechanism underlying this action is associated with improvement in antioxidant defense system.

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.

Antioxidant, anti-inflammatory, and antiapoptotic effects of virgin coconut oil against antibiotic drug gentamicin-induced nephrotoxicity via the suppression of oxidative stress and modulation of iNOS/NF-ĸB/caspase-3 signaling pathway in Wistar rats.

Gentamicin is an effective antibiotic against severe infections; however, its major side effect is oxidative nephrotoxicity. We explored whether virgin coconut oil (VCO) could mitigate gentamicin-induced nephrotoxicity. Rats were fed with VCO-supplemented diet for 16 days against renal toxicity induced by gentamicin (100 mg/kg bw, ip) from Day 11 to 16. Gentamicin caused marked elevated serum urea, uric acid, and creatinine levels, followed by considerable depletion in renal antioxidant enzymes, glutathione (GSH), while the malondialdehyde (MDA) level increased significantly. It significantly increased renal cytokines and nitric oxide (NO) levels, confirmed by renal histopathology. The expression of inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-ĸB), and caspase-3 was prominently increased. VCO-supplemented diet significantly modulated the levels of biochemical indices, downregulated the expression of NO, iNOS, NF-ĸB, caspase-3, cytokines, and alleviated histopathological lesions. VCO protects against gentamicin-induced nephrotoxicity; thus, it could be a promising dietary supplement for patients undergoing gentamicin treatment. PRACTICAL APPLICATIONS: Gentamicin is an efficacious clinical antibiotic used against severe infections; however, the robust body of evidence indicates that the nephrotoxic side effect constrained its use. Virgin coconut oil (VCO) is an edible oil with growing human consumption and pharmacological effects. Our study has reported herein, for the first time, that VCO diet prevented the nephrotoxicity of gentamicin. Dietary supplementation of this oil could be beneficial in alleviating the nephrotoxic side effect of gentamicin in patients.

Abrogation of Hepatic Damage Induced by Anticancer Drug Methotrexate by Zobo (Hibiscus sabdariffa extract) Supplementation via Targeting Oxidative Hepatotoxicity in Rats.

Clinical use of methotrexate (MTX) in cancer chemotherapy is limited due to its side effects, notably associated with increased oxidative stress and hepatotoxicity. Zobo is an aqueous extract of Hibiscus sabdariffa known to contain natural antioxidants. The present study investigated the hepatoprotective effect of zobo drink (ZD) on MTX-induced oxidative stress and hepatotoxicity in rats. Rats randomized to control group received distilled water orally; MTX group received intraperitoneal (ip) injection of MTX (20 mg/kg) on day 11; ZD + MTX group was administered ZD (10 ml/kg) for 14 days and was injected with MTX on day 11. Three days after MTX injection, enzyme markers of liver injury, protein profile, and bilirubin were assessed in serum. Hepatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of lipid peroxidation were estimated. Histopathological changes were carried out on the liver tissue. MTX induced prominent oxidative hepatotoxicity demonstrated by significant (p < .01) increases in serum liver enzymes and bilirubin, while protein profile was markedly reduced (p < .05). Hepatic activities of SOD, CAT, and GPx considerably decreased, whereas lipid peroxidation increased significantly in the MTX group compared to control. By contrast, ZD administration attenuated and restored the markers of liver injury, hepatic antioxidant enzymes, and lipid peroxidation near to control, while histopathological alterations were ameliorated compared to the MTX group. ZD affords superior protection against MTX-induced oxidative hepatotoxicity via improvement in antioxidant defense systems in rats. ZD could be a potent natural product against hepatotoxicity associated with MTX chemotherapy in cancer patients.

Beneficial role of virgin coconut oil supplementation against acute methotrexate chemotherapy-induced oxidative toxicity and inflammation in rats.

BACKGROUND: Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid agent whose efficacy is limited by marked organ toxicities associated with oxidative stress. The study investigated beneficial effect of virgin coconut oil (VCO) supplementation on MTX-induced oxidative stress and inflammation in rats. METHODS: Rats were divided into 4 groups (n = 6): Control, MTX (20 mg/kg bw), VCO (5%) + MTX and VCO (15%) + MTX. The pre-treatment with VCO for 14 days was followed by single intraperitoneal injection of MTX and the rats were sacrificed after 3 days. Serum activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and levels of reduced glutathione (GSH) and malondialdehyde (MDA) were determined. Interleukin-6 (IL-6), C-reactive protein (CRP) and nitric oxide (NO) levels were also evaluated. RESULTS: MTX induced a distinct diminution in serum activities of oxidative stress markers (SOD, CAT, GPx and GSH), while lipid peroxidation considerably increased demonstrated by MDA level. Similarly, levels of IL-6, CRP and NO increased prominently in MTX control rats. The VCO supplementation markedly enhanced resistance to the MTX-induced biochemical alterations in rats. CONCLUSION: VCO can be a useful adjuvant natural product in MTX chemotherapy by reducing oxidative stress and pro-inflammatory responses.

Repeatedly heated palm kernel oil induces hyperlipidemia, atherogenic indices and hepatorenal toxicity in rats: Beneficial role of virgin coconut oil supplementation.

BACKGROUND: The literature reports that the health benefits of vegetable oil can be deteriorated by repeated heating, which leads to lipid oxidation and the formation of free radicals. Virgin coconut oil (VCO) is emerging as a functional food oil and its health benefits are attributed to its potent polyphenolic compounds. We investigated the beneficial effect of VCO supplementation on lipid profile, liver and kidney markers in rats fed repeatedly heated palm kernel oil (HPO). METHODS: Rats were divided into four groups (n = 5). The control group rats were fed with   a normal diet; group 2 rats were fed a 10% VCO supplemented diet; group 3 administered 10 ml HPO/kg b.w. orally; group 4 were fed 10% VCO + 10 ml HPO/kg for 28 days. Subsequently, serum markers of liver damage (ALT, AST, ALP and albumin), kidney damage (urea, creatinine and uric acid), lipid profile and lipid ratios as cardiovascular risk indices were evaluated. RESULTS: HPO induced a significant increase in serum markers of liver and kidney damage as well as con- comitant lipid abnormalities and a marked reduction in serum HDL-C. The lipid ratios evaluated for atherogenic and coronary risk indices in rats administered HPO only were remarkably higher than control. It was observed that VCO supplementation attenuated the biochemical alterations, including the indices of cardiovascular risks. CONCLUSIONS: VCO supplementation demonstrates beneficial health effects against HPO-induced biochemical alterations in rats. VCO may serve to modulate the adverse effects associated with consumption of repeatedly heated palm kernel oil.