Protective Effects of Graviola and its Nanoparticles against Hyperthyroidism-Induced Kidney and Thyroid Injuries in Rats through Antioxidant and Anti-Apoptotic Pathways

Hyperthyroidism is a prevalent endocrine disorder that disrupts several physiological processes and is often linked to renal and thyroid dysfunction through mechanisms involving oxidative stress, apoptosis, and fibrosis. This study aimed to evaluate the pathological consequences of hyperthyroidism and the protective role of graviola and its nanoparticle formulations on renal and thyroid function in male rats. Eighty male rats (120–140 g) were randomly divided into eight groups: control, hyperthyroid (L-thyroxine, 0.3 mg/kg), graviola (200 mg/kg), graviola nanoparticles (200 mg/kg), and co-treated groups receiving L-thyroxine with graviola or its nanoparticles at doses of 200, 100, or 50 mg/kg body weight for 28 days. On the 29th day, blood and tissue samples were collected for biochemical, oxidative stress, gene expression analyses and histopathological examination. Hyperthyroidism elevated serum T3, T4, and MDA levels while reducing TSH, creatinine, urea, TAC, GSH, altered expression of Bax, TGF-β1, IL-1β, and Bcl-2 and marked tissue degeneration were also observed. Co-administration of graviola or its nanoparticles mitigated these alterations. The greatest improvement in biochemical parameters, gene expression and histological findings was recorded with graviola nanoparticles at 50 mg/kg. In conclusion, the findings of this study confirm that graviola, particularly in its nanoform, has a strong protective effect against the complications of hyperthyroidism. It significantly improved thyroid and kidney functions, reduced oxidative stress and apoptosis, and restored the balance of gene expression related to inflammation and cellular damage. These results highlight the promising potential of graviola and its nanoparticles as natural therapeutic agents for supporting the treatment and prevention of disorders associated with hyperthyroidism.