Curcumin attenuates high glucose-induced apoptosis in renal tubular epithelial cells by enhancing the Nrf2/heme oxygenase-1 antioxidant pathway.

BACKGROUND

Diabetic nephropathy (DN) is a major complication that arises from diabetes. Curcumin, a bioactive compound with antioxidant properties, has been shown to modulate multiple cellular pathways and thereby mitigate tissue damage.

AIM: To explore the influence of curcumin on high glucose-triggered apoptosis in renal tubular epithelial cells.

METHODS

Sprague-Dawley rats were divided into control, diabetic, and curcumin treatment groups (n = 10/group). Renal function markers (neutrophil gelatinase-associated lipocalin, KIM-1, and urinary albumin) were assessed, and renal tissues were analyzed using histopathology, TUNEL assays, and immunohistochemistry. Renal tubular epithelial cells were cultured under normal (5.5 mmol/L) or high glucose (30 mmol/L) conditions, with or without curcumin. Apoptosis, reactive oxygen species (ROS) levels, and Nrf2/heme oxygenase-1 (HO-1) signaling pathway markers were evaluated using flow cytometry, quantitative polymerase chain reaction, and immunohistochemistry.

RESULTS

Curcumin improved renal function markers and reduced renal tubular apoptosis in diabetic rats. In vitro, it suppressed high glucose-induced apoptosis and ROS production, while activating the Nrf2/HO-1 antioxidant pathway (upregulated Nrf2 and HO-1 expression, and downregulated Keap1) and modulating the Bcl-2/Bax apoptotic balance (downregulated Bax and upregulated Bcl-2), demonstrating sequential protection against oxidative stress followed by apoptosis inhibition.

CONCLUSION

Curcumin protects against high glucose-induced renal tubular epithelial apoptosis by enhancing Nrf2/HO-1 signaling to reduce oxidative stress and apoptosis, indicating its therapeutic potential for DN.