Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment

Jingming Xu, Shichun Sun, Wei Wei, Jianmin Fu, Wenbo Qi, Lucien C. Manchester, Dun Xian Tan, Russel J. Reiter

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The bipyridyl herbicide, diquat, is a potent prooxidant that generates superoxide anions through redox cycling in vivo. Exposure to elevated levels of this compound causes acute hepatic and renal toxicity as well as death in rodents. In the present study, we investigated whether melatonin, a free radical scavenger and antioxidant, could protect against diquat-induced hepatic and renal damage and whether the indole would improve survival of Kunming mice given a lethal dose of diquat. When mice were intraperitoneally (i.p.) given a single dose of diquat (50 mg/kg body weight), liver and kidney injuries were observed at 6 hr as indicated by elevated serum levels of both alanine aminotransferase (ALT) activity and blood urea nitrogen (BUN). In addition, lipid peroxidation levels in both liver and kidney showed significant increases as shown by elevated concentrations of F2-isoprostanes. The administration of melatonin (20 mg/kg) 30 min before the diquat injection resulted in a significant reduction in serum levels of ALT and BUN as well as hepatic and renal F2-isoprostanes levels. For the survival study, 75 mg/kg diquat was administered i.p. into mice to induce acute death. Without melatonin treatment, 10 of 23 (43.5%) mice died within 24 hr after diquat injection. Pretreatment with melatonin (20 mg/kg) 30 min prior to the injection of diquat and thereafter at 4-hr intervals until the end of the observation period (24 hr), reduced the death rate to two of 22 (9.1%) mice. Chi-squared test revealed a significant difference with P ≤ 0.05. In conclusion, melatonin, a broad spectrum antioxidant, reduces hepatic and renal damage and lowers the death rate in diquat-treated mice.

Original languageEnglish (US)
Pages (from-to)166-171
Number of pages6
JournalJournal of pineal research
Volume42
Issue number2
DOIs
StatePublished - Mar 1 2007

Keywords

  • Diquat
  • F-isoprostanes
  • Free radicals
  • Lipid peroxidation
  • Melatonin
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology

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