Abstract
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.
Highlights
The most common endocrine disease in middle-aged and geriatric cats is hyperthyroidism (FHT), which is characterized by an excess of thyroid hormones, namely triiodothyronine (T3) and thyroxine (T4) [1]
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
We have recently demonstrated that the dietary supplementation of an antioxidant mixture, containing quercetin (Q), resveratrol (R), curcumin, and vitamin E, counteracts both the oxidative stress and the side-effects elicited by MMI in hyperthyroid cats [20]
Summary
The most common endocrine disease in middle-aged and geriatric cats is hyperthyroidism (FHT), which is characterized by an excess of thyroid hormones, namely triiodothyronine (T3) and thyroxine (T4) [1]. Some studies underlined the relationship between an excess of thyroid hormones and other diseases, such as chronic kidney failure, pulmonary hypertension, and chronic heart disorders [3,4,5]. The gold standard therapy for FHT is the treatment with radioactive iodine. An alternative approach is surgical thyroidectomy, of which application is limited by concurrent geriatric problems that are likely to increase the risk of anesthesia-related complications [6]. Pharmacotherapy with thyroid peroxidase inhibitors, so-called anti-thyroid drugs, is often the sole treatment option for FHT, and methimazole (MMI) is the drug of choice [7]
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