The Changes Of MRNA Expression Of NF-κBP65 MCP-1 In Rats Administrated By Paraquat And Effect On Anisodamine Preventing Paraquat Toxicity

Objective The purpose of this study was to pursue the toxicology of paraquatand to determine whether anisodamine prevented paraquat toxicity and itsmechanism.Methods and Results There were two parts in this study. In the first part, fourhours after paraquat administrated, the mRNA expression of NF-кBP65,MCP-1 inlung and liver of rats was respectively detected by semi-quantitative RT-PCRcompared to normal control group. In the second part, rats were randomly dividedinto three groups: normal control group, anisodamine group and paraguat group. Ratsof the last two groups were administrated by paraquat. Two hours after paraquatinjection, rats of anisodamine group were treated with anisodamine (30mg/kg i.p,three times everyday). The PaO2 and the plasma concentration of TNF-α, T-AOC,ALT in rats of the paraquat group was measured at 3,5,7 days(T1,T2,T3). Compared tothat of normal control group, mRNA expression of NF-кBP65, MCP-1 wassignificantly increased (P<0.01) in rats administrated by paraquat in the first part.Inthe second part, the plasma concentration of TNF-α, ALT in rats of paraquat group atthree time points was increased too, while T-AOC, PaO2 reduced. There weresignificantly different in results between normal control group and paraquat group.Treatment with anisodamine markedly attenuated the increase in plasma content ofTNF-αat three time points compared to that of paraquat group (P<0.01), but theywere higher than that of normal control group (P<0.05). It also attenuated the decreasein results of T-AOC, PaO2 as well as it attenuated the increase in ALT in anisodaminegroup. Compared to the paraquat group, there were significantly different in results ofT-AOC, PaO2, ALT at T3 point in anisodamine group (P<0.01).Conclution The mRNA expression of NF-кBP65,MCP-1 in lung and liver ofrats administrated by paraquat increased significantly, and the plasma concentration ofTNF-αincreased too. These results suggested that NF-кBP65,MCP-1, TNF-αmaybe involved in the pathogenesis induced by paraquat. Anisodamine inhibitedparaquat-induced the increase in plasma concentration of TNF-αand ALT, attenuatedthe decrease in results of T-AOC, PaO2, mitigated lung and liver injury and may thusbe used as a therapeutic agent for paraquat poisoning.