Combined but not single administration of vitamin C and l-carnitine ameliorates cisplatin-induced gastric mucosa damage in male rats

Can J Physiol Pharmacol. 2018 Aug;96(8):830-838. doi: 10.1139/cjpp-2017-0751. Epub 2018 Apr 20.

Abstract

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H2O2) and decreased activities of antioxidant (superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase) and non-antioxidant (reduced glutathione) enzymes. These deleterious events were accompanied with significant increases in pro-inflammatory cytokines and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase. However, the administration of both vitamin C and l-carnitine, and not either of the two showed additive effects in attenuating the adverse effects of cisplatin. The histological results agreed with the biochemical assays. The study concluded that the combined administration of vitamin C and l-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissue.

Keywords: antioxidants; antioxydants; cisplatin; cisplatine; infiltration de neutrophiles; l-carnitine; neutrophil infiltration; nitric oxide synthase; oxyde nitrique synthase; vitamin C; vitamine C.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Ascorbic Acid / administration & dosage*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use
  • Biomarkers / metabolism
  • Body Weight / drug effects
  • Carnitine / administration & dosage*
  • Carnitine / pharmacology
  • Carnitine / therapeutic use
  • Cell Count
  • Cisplatin / adverse effects*
  • Cytokines / metabolism
  • Feeding Behavior
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology*
  • Hydrogen Peroxide / metabolism
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mucus / metabolism
  • Nitric Oxide Synthase / metabolism
  • Oxidants / metabolism
  • Peroxidase / metabolism
  • Rats, Wistar

Substances

  • Antioxidants
  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Oxidants
  • Malondialdehyde
  • Hydrogen Peroxide
  • Peroxidase
  • Nitric Oxide Synthase
  • Ascorbic Acid
  • Cisplatin
  • Carnitine