Modulation of GBP5/NLRP3 inflammasome signaling by sumatriptan in experimental thyrotoxic cardiomyopathy in rats

Objectives: Excess thyroid hormone adversely affects cardiovascular structure and function and may ultimately lead to dilated cardiomyopathy. This study investigated the cardioprotective effects of low-dose sumatriptan against hyperthyroidism-induced cardiomyopathy in male albino rats, with particular emphasis on the involvement of the guanylate-binding protein 5/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (GBP5/NLRP3) inflammatory pathway. Materials and Methods: Forty-four male albino rats were randomly assigned to four groups (11 rats/group): control, sumatriptan-treated, hyperthyroid, and hyperthyroid treated with sumatriptan. Hyperthyroidism was induced by daily intraperitoneal administration of levothyroxine sodium (100 mg/kg) for four weeks. Sumatriptan (0.1 mg/kg, intraperitoneally) was administered daily for the same period. Thyroid hormones, cardiovascular parameters, cardiac hypertrophy, oxidative stress, inflammatory biomarkers, fibroblast growth factor 23, histopathology, and myocardial GBP5 expression were evaluated. Results: Hyperthyroidism significantly increased circulating thyroid hormone concentrations, induced cardiac hypertrophy and tachycardia, elevated systolic blood pressure, reduced diastolic blood pressure, and promoted oxidative stress, inflammation, and myocardial injury. Sumatriptan did not significantly alter thyroid hormone concentrations but significantly attenuated cardiac hypertrophy, reduced heart rate, decreased creatine kinase-myocardial band levels, restored superoxide dismutase activity, and suppressed fibroblast growth factor 23, GBP5 expression, and NLRP3 inflammasome activation. Histopathological examination demonstrated marked improvement in myocardial architecture and attenuation of fibrosis in sumatriptan-treated hyperthyroid rats. Conclusions: Low-dose sumatriptan protects against hyperthyroidism-induced cardiomyopathy by attenuating oxidative stress, inflammation, and fibrosis through modulation of the GBP5/NLRP3 inflammatory pathway without altering thyroid hormone status. These findings identify a potential therapeutic mechanism; however, confirmation in clinical studies is required.