Girolami Flavia, Candellone Alessia, Jarriyawattanachaikul Watanya, Meineri Giorgia, Nebbia Carlo, Badino Paola
Department of Veterinary Sciences, University of Torino, L. go Braccini 2, 10095 Grugliasco, TO, Italy.
Vet Sci. 2021 Oct 8;8(10):220. doi: 10.3390/vetsci8100220.
The treatment of choice for feline hyperthyroidism is the administration of the antithyroid drug methimazole. Both the endocrinopathy and the drug adverse reactions (e.g., hepatotoxicosis, gastrointestinal disorders, and renal injury) are partly due to oxidative stress and redox unbalance. This study investigated the free radical production and the impairment of the antioxidant barrier induced by methimazole in an in vitro model of feline renal epithelium. The protective effects of quercetin and resveratrol were also explored. CRFK cells were incubated with a methimazole concentration equivalent to the maximum plasma levels in orally treated cats (4 µM), in the presence or absence of either one of the two selected antioxidants at different time-points (up to 72 h). Cell viability, ROS production, GSH levels, and mRNA expression of antioxidant enzymes (i.e., CAT, SOD, GPx, and GST) were assessed. Methimazole impaired cell viability and increased ROS levels in a time-dependent manner. Similarly, GSH content and CAT, SOD, and GPx3 expression were higher compared with control cells. Such effects were significantly counteracted by quercetin. These results provide new insights about the mechanisms underlying the methimazole-related side effects frequently observed in hyperthyroid cats. They also support the use of quercetin in the management of feline hyperthyroidism.
猫甲状腺功能亢进的首选治疗方法是给予抗甲状腺药物甲巯咪唑。内分泌病和药物不良反应（如肝中毒、胃肠道疾病和肾损伤）部分归因于氧化应激和氧化还原失衡。本研究在猫肾上皮细胞的体外模型中，研究了甲巯咪唑诱导的自由基产生和抗氧化屏障的损伤。还探讨了槲皮素和白藜芦醇的保护作用。将CRFK细胞与相当于口服治疗猫的最大血浆水平（4µM）的甲巯咪唑浓度孵育，在不同时间点（长达72小时）存在或不存在两种选定抗氧化剂中的一种。评估细胞活力、活性氧生成、谷胱甘肽水平和抗氧化酶（即过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶）的mRNA表达。甲巯咪唑以时间依赖性方式损害细胞活力并增加活性氧水平。同样，与对照细胞相比，谷胱甘肽含量以及过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶3的表达更高。槲皮素可显著抵消这些作用。这些结果为甲状腺功能亢进猫中经常观察到的与甲巯咪唑相关的副作用的潜在机制提供了新的见解。它们还支持槲皮素在猫甲状腺功能亢进管理中的应用。
