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

Abstract

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.