In vitro Evaluation of the Reno-Protective Effects of Captopril and Spironolactone in Streptozotocin-Induced Diabetic Nephropathy: Synergistic Antioxidant and Anti-Inflammatory Mechanisms

Background

Diabetic Nephropathy (DN) is a major complication of diabetes characterized by oxidative stress and inflammation, leading to progressive renal damage. This study aimed to investigate the reno-protective effects of captopril and spironolactone, individually and in combination, against Streptozotocin (STZ)-induced nephrotoxicity in vitro.

Materials and Methods

Normal Rat Kidney Epithelial (NRK-52E) cells were exposed to STZ to mimic oxidative and inflammatory injury. Cells were treated with captopril, spironolactone, or their combination. Cell viability and morphology were evaluated by MTT assay and microscopy. Antioxidant potential was assessed using Total Antioxidant Capacity (TAC) and Ferric Reducing Antioxidant Power (FRAP) assays, while anti-inflammatory activity was examined via protein denaturation assay and western blotting for IL-6, TNF-α, and TGF-β expression.

Results

STZ exposure induced marked oxidative stress, cell death, and inflammation in NRK-52E cells. Captopril and spironolactone treatment significantly improved cell viability, preserved normal morphology, and reduced oxidative and inflammatory responses. Spironolactone exhibited stronger antioxidant activity than captopril, while the combination therapy produced a synergistic effect, restoring antioxidant balance and suppressing inflammatory cytokines more effectively than monotherapy.

Conclusion

Captopril and spironolactone demonstrate significant antioxidant and anti-inflammatory properties, attenuating STZ-induced renal injury. Their combination enhances reno-protection, supporting the potential role of dual therapy in managing diabetic nephropathy. Further studies are needed to validate these findings and assess clinical translation.