Therapeutic benefit of melatonin in 5-fluorouracil-induced renal and hepatic injury

Basic Clin Pharmacol Toxicol. 2024 Mar;134(3):397-411. doi: 10.1111/bcpt.13976. Epub 2024 Jan 15.

Abstract

Nephrotoxicity and hepatotoxicity include increased oxidative stress and apoptosis; as a result, liver and kidney damage are related to its pathogenesis. These are significant side effects caused in cancer patients treated with 5-FU. In the research, 25 rats were divided into five groups, including control, 5-FU and 5-FU + 2.5, 5 and 10 mg/kg melatonin (MEL), and the protective impact of MEL against 5-FU-induced hepatorenal damage in rats was investigated. 5-FU caused significant harm, resulting in severe renal failure and histopathological changes. It also increased BUN, creatinine and hepatic function markers levels while decreasing superoxide dismutase and glutathione peroxidase activity. Additionally, 5-FU led to a notable increase in malondialdehyde content. However, MEL co-administration to rats reversed most biochemical and histologic effects. In the control and MEL + 5-FU groups, the values were comparable. The doses of MEL treatment had a significant positive impact on 5-FU-induced oxidative stress, apoptosis, lipid peroxidation and kidney damage. Our data concluded that MEL has an ameliorative effect on hepatorenal damage caused by 5-FU.

Keywords: apoptosis; hepatocellular carcinoma; histopathology; melatonin.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Fluorouracil / toxicity
  • Humans
  • Kidney
  • Kidney Diseases* / drug therapy
  • Liver
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • Oxidative Stress
  • Rats
  • Superoxide Dismutase / metabolism

Substances

  • Melatonin
  • Fluorouracil
  • Antioxidants
  • Superoxide Dismutase