| Rotenone is a natural pesticides,extracted from the roots and stems of plant species,due to the character of strong pesticide effect and unstable in the presence of light and air,it is widely used in the agriculture,but some epideemiological experts have found that there would be some similar symptoms of parkinson's disease(PD)after long-term exposure of rotenone.Nowadays,the toxicity of rotenone is mainly focused on neurotoxicity studies,and there is little research on visceral toxicity.In this paper,we investigated the effects of rotenone on rats liver toxicity induced by rotenone,the biochemical indexes,the expression of inflammatory factors,the changes of oxidative function and the pathological changes of the liver.Our results suggest that rotenone should be used at the lowest effective concentration to kill pests,thereby reducing toxicity to animals.Sixty SD male rats(180±20 g)were divided into the following five groups: control,dimethyl sulfoxide(DMSO),rotenone low-dose(1 mg/kg),rotenone mid-dose(2 mg/kg)and rotenone high-dose(4 mg/kg)groups.The treatments were orally administered daily for 28 days,rats were euthanized by cervical dislocation,eye blood collection and separation of serum,the liver was rapidly excised.Then we detected the activities of Aspartate transaminase(AST)and Alanine aminotransferase(ALT)in serum;detected indexs of oxidative stress: the activities of Superoxide Dismutase(SOD),Catalase(CAT)and Glutathione peroxidase(GSH-Px),the contents of Malondialdehyde(MDA)and Nitrogen Monoxide(NO)to confirm the oxidative damage of rat liver by rotenone;detected indexs of inflammatory factor:the mRNA expressions of Nuclear factor kappaB(NF-?B),inducible nitric oxide synthase(iNOS),Tumor necrosis factor ?(TNF-?),Cyclooxygenase2(COX-2)and Prostaglandin E2(PGE2),the protein expressions of NF-?B and COX-2 to confirm the inflammation damage of rat liver by rotenone.The results showed that:(1)Different doses of rotenone were treated for 28 days,it was found varying degrees of change on activities of AST and ALT in the serum,The trend was the consistent for both indexs,The DMSO group showed no difference compared with the control group in the activities of AST and ALT(P>0.05),activities of AST and ALT were significantly higher in each of the rotenone groups compared with the control group(P<0.05),furthermore,the changes in expression were dose-dependent.The highest activities of AST and ALT in the high-dose group.(2)The rats were treated with different doses of rotenone for 28 days,it was found varying degrees of reduce on activities of SOD,CAT and GSH-Px,The trend was the consistent for the three indexs,The DMSO group showed no difference compared with the control group in these three indexs(P>0.05),activities of SOD,CAT and GSH-Px were significantly lower in each of therotenone groups compared with the control group(P<0.05 or P<0.05),furthermore,the changes in expression were dose-dependent.The MDA content was significantly higher in each of the rotenone group compared with the control group(P<0.05),furthermore,the changes in expression were dose-dependent.The NO content was significantly higher in mid-and high-group compared with the control group(P<0.05),but it was showed no difference in low-dose group(P>0.05).(3)The rats were treated with different doses of rotenone for 28 days,the mRNA expression levels of NF-?B,iNOS,TNF-?,COX-2 and PGE2 were showed no difference between DMSO group and the control group for any of the factors tested(P>0.05).NF-?B,COX-2 and PGE2 mRNA expression levels were significantly higher in each of the rotenone groups compared with the control group(P<0.05),furthermore,the changes in expression were dose-dependent.iNOS and TNF-?mRNA expression levels showed significant higher in the mid-dose and high-dose groups(P<0.05),not in the low-dose group compared with the corresponding control group(P>0.05).NF-?B protein expression was significantly higher in the mid-and high-dose groups compared with the control group(P<0.05),the low-dose and DMSO groups were not significantly different compared with the control group(P>0.05).The protein expression of COX-2 was significantly higher in each of the rotenone treatment groups compared with the control group(P<0.05),furthermore,the changes in expression were dose-dependent.(4)Rotenone could cause the symptom of infiltration of inflammatory cells in the portal area,atrophy of liver cells,fat vacuoles and the congestion of the hepatic sinusoids in rat liver.Conclusion: rotenone could cause the damage in rat liver via oxidative damage(supressing the activity of antioxidant enzymes and increasing the content of oxidizing substances)and induce expression of inflammatory factors. |
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