| As a kind of insecticide, rotenone has the characteristics of wide insecticidal spectrum, short residue effect, no pollution to the environment and not easy to produce drug resistance. So far the study about rotenone was mainly focused on Central Nervous System, especially the pathogenesis of Parkinson’s disease. But the study about the toxicity of rotenone to main organ was very deficiency. Through the toxicity test of rotenone on rats, this study res each the toxicity and its mechanism of the kidney.Acute toxicity test:Total 70 male SD rats weighting 180～200 g were divided randomly into 7 groups. The dosage was 8,16,30,57,108,206 mg/kg body weight and DMSO group was given the same dose of DMSO. Rats were intragastrically administered with rotenone and clinical signs and histopathological changes were observed. Postmortem examination of the dead rats, taking heart, liver, spleen, stomach, kidney, lung and other tissues did HE staining observation.Subchronic toxicity test:Total 60 male SD rats were randomly divided into five groups. Group Ⅰ:normal rats orally received nothing; Group Ⅱ:normal rats orally received only the DMSO; Group Ⅲ:rats orally received rotenone at a dose of 1 mg/kg; Group Ⅳ:rats orally received rotenone at a dose of 2 mg/kg; Group Ⅴ:rats orally received rotenone at a dose of 4 mg/kg. In gavage for 28 days, rats were euthanized by cervical dislocation. Through the blood biochemical indexes of urea nitrogen (BUN), creatinine (Cr), uric acid (UA) and kidney tissues of OM, TEM to observe rotenone on rat kidney damage. By oxidative stress-related biochemical indicators of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were measured to observe the degree of renal oxidative damage. By detecting kidney tissue mitochondrial membrane potential and voltage-dependent anion channel, cytochrome C, Caspase-9 and Caspase-3 protein expression levels to observe its effect on apoptosis.The results showed that:(1)The median lethal dose (LD50) and 95% confidence limit of rotenone were respectively 34.10 mg/kg body weight and 23.44～49.62 mg/kg body weight. The main acute toxicity in rats were nausea, dyspneic respiration, convulsions, ataxia. These clinical signs were dose-dependent. Histopathological alterations included myocardial cell swelling, vacuolization deformation, the cytoplasm of dye powder particles; central venous congestion of liver, liver cells visible fat vacuoles; lung part widened alveolar septum and inflammatory cell infiltration; renal tubular epithelial cell vacuoles and dye powder particles.(2)Rotenone intoxication in rats could reduce the body weight and increase kidney index. The results showed that serum BUN, Cr, UAcontent increased in rotenone administration groups. We observed kidney tissue appeared obvious vacuolar degeneration and inflammatory cell infiltration. This showed that rotenone could cause certain damage to the kidney of rats. Renal tissue SOD, GSH-Px decreased and GSH, MDA, ROS levels increased. It indicated that rotenone could cause oxidative damage to the kidney tissue. It could prompt the mitochondrial membrane potential drop, made the rat kidney VDAC, cytochrome C, Caspase-9 and Caspase-3 protein expression increase. This suggested that rotenone could induce apoptosis through the mitochondrial pathway.Conclusion:The median lethal dose (LD50) of rotenone are 34.10 mg/kg body weight, rotenone caused acute toxicity, damaging heart, livers, lungs, kidneys, stomach and other organs of SD rats. Rotenone could cause certain damage to the kidneys of rats and the mechanism might be through its oxidative damage of kidney tissue and mitochondrial pathway mediated apoptosis. |
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