RESUMO
AIMS: Chronic kidney disease (CKD) is a global non-communicable health problem. Fibrosis is considered the base and the fate of CKD; thus, the goal of this study was to evaluate the effects of sodium molybdate on cisplatin-induced CKD model and demonstrate the possible involved mechanisms. MATERIALS AND METHODS: In cisplatin model, Wistar rats were challenged with cisplatin (1 mg/kg, i.p.) twice weekly for ten weeks. Sodium molybdate (100 and 200 mg/kg, orally) was given one-week prior cisplatin and was continued daily for the next ten weeks. KEY FINDINGS: Administration of sodium molybdate amended kidney function and significantly reduced the pathological changes in renal histopathological sections. Moreover, it modulates oxidative stress parameters by increasing the levels of SOD and GSH and decreasing the level of MDA. Likewise, in renal homogenate, sodium molybdate attenuated inflammation that was revealed by NF-κB and TNF-α levels significant reduction. Additionally, it ameliorated fibrosis that was indicated by decreased Masson's trichome staining in cortex and medulla. Immunohistochemical staining of renal sections against TGF-ß1 showed reduction of positive glomerular and tubular protein expression. Additionally, it decreased profibrotic Smad3 level and increased antifibrotic Smad7 level. SIGNIFICANCE: Administration of sodium molybdate demonstrated a hopeful suppressor effect on cisplatin-induced CKD/fibrosis in rat model. This effect may be through the inhibition pof TGF-ß/Smad signaling pathway and up-regulation of Smad7 expression leading to decreased extracellular collagen accumulation. Moreover, they could ameliorate the inflammation through NF-κB and TNF-α levels reduction, decrease in ROS, and retrieval of antioxidant defenses.