The protective effect of hesperidin on the liver of hypothyroid rats mediated by nuclear factor erythroid 2-related factor 2-dependent activation of heme oxygenase 1.

Hypothyroidism (HPO) has been linked to a higher incidence of hepatic lesions. Hesperidin (HSP) is an antioxidant, anti-adipogenic, anti-inflammatory, anti-hyperlipidemic, and anti-apoptotic agent. Therefore, the study aimed to assess the impact of carbimazole (CBZ)-induced HPO on adult albino rats' liver and explore the possible ameliorating effect of Eltroxin (ELT) and HSP. HPO was induced by CBZ (20 mg/kg/day). Rats were allocated into group I: normal control; group II: received CBZ (20 mg/kg/day) only; group III: received CBZ and HSP (200 mg/kg/day); and group IV: received CBZ and ELT (0.045 mg/kg/day). HSP and ELT attenuated dyslipidemia associated with HPO. HSP and ELT also significantly decreased elevated malondialdehyde and increased reduced glutathione levels and superoxide dismutase and catalase activities. Also, they markedly inhibited the expression of nuclear factor kappa B, inducible nitric oxide synthase, interleukin (IL)-1ß, tumor necrosis factor-alpha, and alpha-smooth muscle actin. On the other hand, HSP successfully elevated nuclear factor erythroid 2-related factor 2, heme oxygenase 1, IL-37, proliferating cell nuclear antigen, and B-cell lymphoma 2 levels. Moreover, HSP decreased the activity of liver transaminases and increased total protein and albumin levels. HSP showed a protective effect on liver tissues of CBZ-treated rats. Our findings confirmed that HSP is an effective antioxidant that prevents and protects the liver from damage by CBZ. Therefore, HSP is a promising candidate for future use to minimize and alleviate HPO risks.