Department of Experimental Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Port Harcourt, Port Harcourt, Rivers, Nigeria.
J Basic Clin Physiol Pharmacol. 2020 Dec 17;32(6):1065-1074. doi: 10.1515/jbcpp-2020-0136.
Acetaminophen (paracetamol) and alcohol are widely consumed as analgesic/antipyretic and recreational agent, respectively. High doses of both agents induce liver and male reproductive toxicities. This study investigated the toxicological outcome of concurrent administration of paracetamol and ethanol in the liver and testis in mice.
Animals were gavaged paracetamol (250 mg/kg), ethanol (3 g/kg) or paracetamol + ethanol for 2 d. Some groups were sacrificed 12 h after the last dose, while others were sacrificed 21 d posttreatment for reversibility study. Control group received carboxymethylcellulose sodium (0.2%). Serum levels of liver biochemical indices and epididymal sperm were analysed. Histopathological analysis of the liver and testis were also performed.
Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin in serum were elevated (p<0.001); whereas albumin and total protein were reduced (p<0.001) in paracetamol or ethanol groups compared to control. In the combination group, only mild elevation of ALT (p<0.05) was observed. Additionally, hepatocyte necrosis occurred in the livers of paracetamol and ethanol groups, while only mild inflammatory changes were seen in the combination group. All liver indices were normal in reversibility study animals. Furthermore, sperm count, motility, viability and morphology did not change in all treated animals, except that sperm count was decreased (p<0.05) in paracetamol group. Testis histology of all animal groups were normal.
The results demonstrated that simultaneous treatment with acute paracetamol and ethanol doses will possibly minimize hepatotoxicity and reduction of epididymal sperm reserve by the individual agents, and the toxicities are reversible.
对乙酰氨基酚(扑热息痛)和酒精分别作为止痛/退热和解热剂而被广泛使用。两者的高剂量都会导致肝和男性生殖毒性。本研究旨在研究扑热息痛和乙醇同时给药对小鼠肝脏和睾丸的毒理学影响。
动物灌胃给予扑热息痛(250mg/kg)、乙醇(3g/kg)或扑热息痛+乙醇,连续 2 天。部分组在最后一次给药后 12 小时处死,其余组在治疗后 21 天处死进行可逆性研究。对照组给予羧甲基纤维素钠(0.2%)。分析血清肝生化指标和附睾精子水平。还进行了肝和睾丸的组织病理学分析。
与对照组相比,血清碱性磷酸酶(ALP)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和胆红素升高(p<0.001);而白蛋白和总蛋白降低(p<0.001)在扑热息痛或乙醇组中。在联合组中,仅观察到 ALT 轻度升高(p<0.05)。此外,扑热息痛和乙醇组的肝细胞发生坏死,而联合组仅出现轻度炎症改变。在可逆性研究动物中,所有肝脏指标均正常。此外,除扑热息痛组精子计数减少(p<0.05)外,所有处理动物的精子活力、活力和形态均未改变。所有动物组的睾丸组织学均正常。
结果表明,同时给予急性扑热息痛和乙醇剂量可能会最小化两种药物单独引起的肝毒性和附睾精子储备减少,且毒性是可逆的。