Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment.
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 F(2)-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 F(2)-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 < or = 0.05. In conclusion, melatonin, a broad spectrum antioxidant, reduces hepatic and renal damage and lowers the death rate in diquat-treated mice.
Xu
Jingming
J
Division of Life Science and Technology, Ocean University of China, Qingdao, China.
Sun
Shichun
S
Wei
Wei
W
Fu
Jianmin
J
Qi
Wenbo
W
Manchester
Lucien C
LC
Tan
Dun-Xian
DX
Reiter
Russel J
RJ
D000818:Animals; D004178:Diquat / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D006540:Herbicides / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008550:Melatonin / Q000502:physiology*; D051379:Mice; D009026:Mortality; D010084:Oxidation-Reduction
D006540:Herbicides; D004178:Diquat; D008550:Melatonin