Elazab Sara T, Samir Omar, Abass Marwa E
Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura,35516, Egypt.
Laboratory Animal Resource Center in Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Vet World. 2021 Jul;14(7):1901-1907. doi: 10.14202/vetworld.2021.1901-1907. Epub 2021 Jul 25.
Fipronil (FPN) is a potent pesticide that is heavily used around the world in agriculture. However, its irrational use could potentially have deleterious effects on animals and humans. The present study aimed to investigate the ability of sitagliptin (Sit) and losartan (LOS), when used both individually or concurrently, to guard rat liver against the acute hepatotoxicity caused by FPN.
Forty-two adult male Wistar rats were equally divided into seven groups (6/group). Group I (control) received normal saline (0.5 mL/rat, vehicle for all treatments) by gavage once daily for 10 days. Group II received oral Sit (10 mg/kg body weight [BW]) daily for 10 days and Group III received oral LOS (5 mg/kg BW) daily for 10 days. Group IV received oral FPN (19.4 mg/kg BW; 1/5 of the oral LD) for the past 5 days of the study. Groups V and VI received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) daily, respectively, 5 days prior and 5 days during FPN administration (19.4 mg/kg BW). Group VII received oral Sit (10 mg/kg BW) and LOS (5 mg/kg BW) for 10 days with daily FPN during the past 5 days. After the end of the treatment period, the rats were humanely sacrificed and blood and liver tissue samples were collected for biochemical analysis and histopathological and immunohistochemical investigations.
FPN administration resulted in elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase serum concentrations as well as increased malondialdehyde levels and reduced catalase, superoxide dismutase, glutathione peroxidase, and glutathione activity. The histopathological investigation showed disorganization of the hepatic cords and focal necrosis of the hepatocytes in FPN-intoxicated rats. Furthermore, the immunohistochemical examination showed that hepatic caspase-3 was overexpressed in the FPN-treated rats. The administration of Sit and LOS before and alongside FPN markedly mitigated the alterations caused by FPN and the hepatoprotective effects were more prominent in the combination group.
Sit and LOS, both individually or in combination, confers considerable hepatoprotection against FPN-induced hepatotoxicity.
氟虫腈（FPN）是一种强效杀虫剂，在全球农业中被大量使用。然而，其不合理使用可能对动物和人类产生有害影响。本研究旨在探究西他列汀（Sit）和氯沙坦（LOS）单独使用或联合使用时，对大鼠肝脏免受FPN所致急性肝毒性的保护能力。
42只成年雄性Wistar大鼠平均分为7组（每组6只）。第I组（对照组）每天经口给予生理盐水（0.5 mL/只，所有处理的赋形剂），持续10天。第II组每天口服Sit（10 mg/kg体重[BW]），持续10天，第III组每天口服LOS（5 mg/kg BW），持续10天。在研究的最后5天，第IV组口服FPN（19.4 mg/kg BW；口服半数致死量的1/5）。第V组和第VI组分别在FPN给药前5天和给药期间（19.4 mg/kg BW）每天口服Sit（10 mg/kg BW）和LOS（5 mg/kg BW）。第VII组在过去5天每天口服Sit（10 mg/kg BW）和LOS（5 mg/kg BW），持续10天，并在过去5天每天给予FPN。治疗期结束后，对大鼠实施安乐死并采集血液和肝脏组织样本，用于生化分析、组织病理学和免疫组织化学研究。
给予FPN导致血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶浓度升高，丙二醛水平增加，过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽活性降低。组织病理学检查显示，FPN中毒大鼠肝索紊乱，肝细胞局灶性坏死。此外，免疫组织化学检查显示，FPN处理的大鼠肝脏中caspase-3过度表达。在FPN给药前及给药期间给予Sit和LOS可显著减轻FPN引起的改变，联合用药组的肝保护作用更显著。
Sit和LOS单独或联合使用均可对FPN诱导的肝毒性提供显著的肝保护作用。
