Protective effects of metformin against aluminum phosphide-induced acute hepato-renal damage in rats: An experimental approach.

Phosphine (PH3), from hydrolysis of magnesium, zinc, and aluminum phosphide (AlP), is a rodenticide and insecticide which is used to avoid losses of the agriculture products. However, using of this agent may affect the human health, in a way that poisoning with AlP has a high rate of mortality and morbidities. This study determined the ameliorative effects of metformin (MET) on AlP-induced hepato- and nephro-toxicity in Wistar rats. Male rats were randomly divided into four experimental groups. Group I was the control group received coconut oil by oral gavage, group II was the model group received AlP (12 mg/kg) distributed in coconut oil by oral gavage, group III received MET (200 mg/kg; i.p.), and group IV received MET (200 mg/kg; i.p.) 30 min after intoxication. After 24 h, the serum, liver and kidney tissues were collected for histopathological and biochemical investigations. The levels of kidney function markers, blood urea nitrogen and creatinine, and liver function markers, ALP, AST and ALT, in the plasma were increased significantly followed by AlP intoxication. The results revealed that phosphine causes a significant enhancement of lipid peroxidation, while decreases the activity of superoxide dismutase in both liver and kidney tissues. Furthermore, phosphine significantly induced the up-regulation of TNF-α and phosphorylation of NF-κB in target tissues. Overall, treatment with MET abolished aforementioned alterations resulted by AlP intoxication. Furthermore, histological evaluation indicated a deleterious effect of AlP on the liver and kidney tissues along with marked increase in kidney and liver injury scores, which is mitigated by MET administration. According to our results, although metformin could not bring the changes to the level of the control group, it was indicated that this drug might possess a protective effect against AlP-induced hepato and nephrotoxicity by inhibiting inflammatory responses and oxidative stress.