Biochemistry Division, Faculty of Science, Cairo University, Giza, 12613, Egypt.
Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Dokki, Giza, 12618, Egypt.
Regul Toxicol Pharmacol. 2019 Oct;107:104400. doi: 10.1016/j.yrtph.2019.05.025. Epub 2019 May 29.
Fipronil (FPN) can induce oxidative tissue damage and may be contemplated as an apoptosis inducer. Our aim is to investigate the possible hepatoprotective roles of garlic or allopurinol (ALP) against fipronil subacute toxicity. Thirty-six mature male albino rats were randomly divided into six groups; the first group was saved as control (C), the 2nd (G) was orally intubated with 500 mg/kg aqueous garlic extract, and the 3rd (A) received 150 mg/L allopurinol in their drinking water. The 4th group (F) was administered 13.277 mg/kg fipronil by gavage, while the 5th (G + F) and 6th (A + F) groups received the same doses of garlic and allopurinol, respectively two hours before fipronil intoxication. Our results revealed that FPN significantly increased the hepatic malondialdehyde, protein carbonyl levels, and the enzymatic activities of superoxide dismutase, catalase, glutathione peroxidase, and xanthine oxidase, but it decreased glutathione-S-transferase compared to the control group. Moreover, FPN exhibited significant up-regulation in the hepatic pro-apoptotic (Bax) and caspase-3 genes expression, down-regulation in the anti-apoptotic (Bcl-2) mRNA gene expression and induced DNA fragmentation. Surprisingly, garlic or allopurinol co-treatment ameliorated the hepatic lipid peroxidation, antioxidants disruption, and apoptosis induced by FPN. In conclusion, garlic and allopurinol relieved the oxidative injury and reduced the fipronil-induced apoptosis probably by improving the tissue antioxidant defense system.
氟虫腈（FPN）可诱导氧化组织损伤，并可能被视为凋亡诱导剂。我们的目的是研究大蒜或别嘌醇（ALP）对氟虫腈亚急性毒性的可能肝保护作用。36 只成熟雄性白化大鼠被随机分为六组；第一组为对照组（C），第二组（G）经口灌胃 500mg/kg 水提大蒜提取物，第三组（A）饮用含 150mg/L 别嘌醇的水。第四组（F）经灌胃给予 13.277mg/kg 氟虫腈，而第五组（G+F）和第六组（A+F）分别在氟虫腈中毒前两小时给予相同剂量的大蒜和别嘌醇。我们的结果表明，FPN 显著增加肝丙二醛、蛋白质羰基水平以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和黄嘌呤氧化酶的酶活性，但与对照组相比，它降低了谷胱甘肽-S-转移酶。此外，FPN 显著上调肝促凋亡（Bax）和 caspase-3 基因表达，下调抗凋亡（Bcl-2）mRNA 基因表达，并诱导 DNA 片段化。令人惊讶的是，大蒜或别嘌醇联合治疗改善了 FPN 诱导的肝脂质过氧化、抗氧化剂破坏和细胞凋亡。总之，大蒜和别嘌醇缓解了氧化损伤，减少了氟虫腈诱导的细胞凋亡，可能是通过改善组织抗氧化防御系统。
