Diphenyl Diselenide Mitigates Renal and Thyroid Dysfunction Associated With Doxorubicin Administration in Wistar Rats

The versatility of doxorubicin (DOX) as an antineoplastic agent makes it a widely prescribed drug against different types of malignancies. However, the clinical use of DOX is associated with nephrotoxicity due to induction of oxidative stress, inflammation and apoptosis. Diphenyl diselenide (DPDS) is an emerging therapeutic agent recognized for its potential prophylactic attributes. This study aimed to elucidate the possible protective efficacy of DPDS against renal and thyroid dysfunction associated with doxorubicin administration. Fifty male Wistar rats were grouped into five (n = 10). Intraperitoneal DOX administration at 7.5 mg/kg of body weight was done once, followed by daily administration of DPDS at 5 and 10 mg/kg for 7 days. DPDS administration protected against DOX-induced increase in biomarkers of renal toxicity (serum urea and creatinine levels), decrease in triiodothyronine (T₃) and thyroxine (T₄) levels, and T₃/T₄ ratio. DOX administration caused significant (p < 0.05) decline in the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase along with diminished glutathione level. Levels of oxidative stress indices, notably, hydrogen peroxide, reactive oxygen and nitrogen species (RONS), and lipid peroxidation levels were significantly (p < 0.05) increased in DOX alone-treated rats. Moreover, DOX administration elevated nitric oxide level and increased myeloperoxidase activity (biomarkers of inflammation) with extensive damage to both the proximal and distal cross-sections of the kidney tissues. However, DPDS effectively mitigated DOX-induced renal oxidative damage by restoring antioxidant enzyme activities, subdual of renal inflammation and pathological lesion. These findings suggest that DPDS could be a viable option for reducing nephrotoxicity in patients treated with DOX.