Cucumeropsis mannii seed oil ameliorates Bisphenol-A-induced adipokines dysfunctions and dyslipidemia.

This study demonstrated the therapeutic potentials of Cucumeropsis mannii seed oil (CMSO) capable of alleviating BPA-induced dyslipidemia and adipokine dysfunction. In this study, we evaluated the effects of CMSO on adipokine dysfunctions and dyslipidemia in bisphenol-A (BPA)-induced male Wistar rats. Six-week-old 36 albino rats of 100-200 g weight were assigned randomly to six groups, which received varied doses of BPA and/or CMSO. The administration of BPA and CMSO was done at the same time for 42 days by oral intubation. The adipokine levels and lipid profile were measured in adipose tissue and plasma using standard methods. BPA induced significant (p < .05) increases in triglycerides, cholesterol, leptin, LDL-C, and atherogenic and coronary risk indices in adipose tissue and plasma, as well as a decrease in adiponectin and HDL-C levels in Group II animals. BPA administration significantly (p < .05) elevated Leptin levels and reduced adiponectin levels. BPA plus CMSO reduced triglycerides, cholesterol, leptin, LDL-C, and atherogenic and coronary risk indices while increasing adiponectin levels and HDL-C in adipose tissue and plasma (p < .05). The results showed that BPA exposure increased adipose tissue as well as serum levels of the atherogenic index, triglycerides, cholesterol, coronary risk index, LDL-C, leptin, and body weight with decreased adiponectin levels and HDL-C. Treatment with CMSO reduced the toxicities caused by BPA in rats by modulating the body weight, adiponectin/leptin levels, and lipid profiles in serum and adipose tissue. This study has shown that CMSO ameliorates BPA-induced dyslipidemia and adipokine dysfunctions. We suggest for further clinical trial to establish the clinical applications.

Downregulation of redox imbalance and iNOS/NF-ĸB/caspase-3 signalling with zinc supplementation prevents urotoxicity of cyclophosphamide-induced hemorrhagic cystitis in rats.

AIM: Cyclophosphamide (CYP) chemotherapy induces bladder toxicity and hemorrhagic cystitis in cancer patients constituting a current clinical concern. Oxidative inflammatory cascades have been implicated as the mechanism contributing to CYP bladder urotoxicity. We thus assayed to explore whether zinc (Zn) supplementation could mitigate CYP-induced urotoxicity and evaluate the possible underlying mechanism in rats. MAIN METHOD: Rats were orally administered Zn (100 mg/kg b.w./day) for 10 days against urotoxicity induced by single injection of CYP (150 mg/kg b.w., ip) on day 7. KEY FINDINGS: CYP significantly depressed bladder activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels, whereas malondialdehyde level was increased prominently. In addition, CYP induced marked increases in the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by histological alterations. CYP prominently increased bladder inducible nitric oxide synthase (iNOS) activity, nuclear factor-kappa B (NF-ĸB) and expression of caspase-3 protein. Zinc supplementation considerably abrogated the bladder urotoxicity by restoring redox balance, proinflammatory and apoptotic cascades and alleviated histopathological changes. SIGNIFICANCE: This is the first to reveal zinc potential to prevent CYP-induced urotoxic hemorrhagic cystitis via restoring redox balance and enhancing anti-inflammatory and antiapoptotic mechanisms in rat bladder.

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.

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.

Moringa oleifera seed oil or virgin coconut oil supplementation abrogates cerebral neurotoxicity induced by antineoplastic agent methotrexate by suppression of oxidative stress and neuro-inflammation in rats.

Methotrexate (MTX) is an effective antineoplastic drug associated with wide organ toxicity. Accumulating evidence implicates oxidative stress to be a leading underlying mechanism of MTX-induced neurotoxicity. The study explores antioxidant potential of virgin coconut oil (VCO) or Moringa oleifera seed oil (MOO) in MTX-induced oxidative stress-mediated cerebral neurotoxicity and inflammation in rats. Rats treated with VCO or MOO (5 ml/kg bw) for 17 days were administered MTX (20 mg/kg, intraperitoneally) on day 14 only. Cerebral activities of acetylcholinesterase, antioxidant enzymes, lipid peroxidation, reduced glutathione and nitric oxide levels as well as cytokines were evaluated. MTX-induced neurotoxic alterations were significantly abrogated by MOO and VCO supplementation via inhibition of cholinesterase, oxidative stress, and anti-inflammatory mechanisms. VCO and MOO showed comparable antioxidant potentials with the standards in DPPH and FRAP assays. VCO and MOO are promising natural oils for modulating MTX neurotoxicity in cancer patients. PRACTICAL APPLICATIONS: Methotrexate chemotherapy induces neurotoxicity in cancer patients, and this is a source of worry for clinicians. This study reports, for the first time, the beneficial health effects of functional food oils, Moringa oleifera seed oil, and virgin coconut oil against anticancer drug methotrexate-induced cerebral neurotoxicity. Supplementation of these natural oils may be beneficial in the prevention of cerebral neurotoxic side effect in cancer patients undergoing methotrexate chemotherapy.

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.

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.