Liver protection of alprostadil against early paraquat-poisoning in rats

GUO Hong-xing; GAO Ke; DENG Qing-wen; LUO Liang; DENG Rui-hua; GUO Min; LIU Liang-ming

Abstract：Objective To observe the liver protection of alprostadil against paraquat -induced early acute liver injury in rats and its mechanism .Methods 72 rats were divided into control group , exposure group and treatment group , among which each 8 rats were subasigned to different durations of exposure by 1, 3 and 7 days.The rats in the exposure and treatment groups received intraperitoneal injections of 20%paraquat (30 mg/kg) to establish the paraquat -poisoning model, while the rats in control group were treated with sterile 0.9%sodium chloride solution (30 mg/kg) only.The rats in treatment group received intraperitoneal injection of alprostadil (1μg/kg) evreyday until excution , while replaced ster-ile saline were given to the other 2 groups .The rats were sacrificed in the corresponding time points and their sera and liv-er tissues were collected .Liver tissues were fixed and stained with hematoxylin and eosin ( HE) for optical microscopic ex-amination.The serum cytokine expression was assessed by ELISA .The inducible nitric oxide synthase ( iNOS) and p53 genes were assessed by RT-PCR, while the liver Caspase-3, -8, -9, and -12 activities were measured by chromo-genic substrate method 3 days after exposure .Results Diffuse large areas of necrosis , inflammatory cell infiltration and impaired hepatocell regeneration were observed in exposure group ;while spared lobular architecture , spotted necrosis , low degreed of congestion and inflammatory cell infiltration were observed in treatment group .The serum TNF-αand IL-1βlevels were significantly higher in exposure group than control group (P<0.01), which was significantly reversed in treat-ment group (P<0.01).Liver Caspase-3, -8, -9 and -12 activities were significantly higher in exposure group than control group (P<0.01), which were also singificantly reversed in treatment group (P<0.01);so was the expression of iNOS and p53 ( P<0.01) .Conclusion Alprostadil can significantly reduce the inflammatory cytokine levels , inhibit the Caspase-3, -8, -9 and -12 activities, and down-regulate the expression of iNOS and p 53 in early paraquat -poi-soning rats, thus provides protective effects against liver injury .