Antioxidant and Anti-Inflammatory Effects of Virgin Coconut Oil Supplementation Abrogate Acute Chemotherapy Oxidative Nephrotoxicity Induced by Anticancer Drug Methotrexate in Rats

Biomed Pharmacother. 2017 Dec;96:905-911. doi: 10.1016/j.biopha.2017.12.008. Epub 2017 Dec 7.

Abstract

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.

Keywords: Chemotherapy; Methotrexate; Nephrotoxicity; Oxidative stress; Virgin coconut oil.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents / adverse effects*
  • Antioxidants / pharmacology*
  • Coconut Oil / pharmacology*
  • Dietary Supplements
  • Glutathione / metabolism
  • Kidney / drug effects
  • Kidney Diseases / chemically induced
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Methotrexate / adverse effects*
  • Oxidation-Reduction / drug effects*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Malondialdehyde
  • Superoxide Dismutase
  • Glutathione
  • Coconut Oil
  • Methotrexate