Curcumin alleviates atrazine-induced nephrotoxicity by enhancing mitophagy through PINK1/Parkin signaling pathway in mice

Abstract

Atrazine (ATR), a widely used herbicide, poses significant environmental and health risks due to its high solubility and adsorption in soil. ATR exposure can lead to nephrotoxicity in humans and animals. Curcumin (Cur), an active compound in Curcuma species, is renowned for its antioxidant and anti-inflammatory properties, with potential to mitigate chronic disease risks. We hypothesized that the addition of Cur could alleviate renal impairment associated with ATR exposure and carried out experiments using mice as subjects. This study investigates whether Cur can attenuate ATR-induced nephrotoxicity in mice by modulating mitophagy and apoptotic pathways. Our findings illustrate that consumption with Cur attenuates nephrotoxicity induced by ATR, as evidenced by lowered serum concentrations of uric acid (UA), blood urea nitrogen (BUN), and creatinine (CRE), established biomarkers of renal injury. Moreover, Curcumin enhances renal antioxidant defense mechanisms in ATR-exposed mice, as indicated by elevated levels of total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase (GSH-Px), alongside reduced levels of malondialdehyde (MDA). Histopathological and electron microscopy analyses further corroborate these findings, showing reduced organelle damage, particularly mitochondrial ridge breakage and vacuolization, and increased autophagic lysosomes. Cur further enhances PINK1/Parkin-mediated autophagy, as evidenced by elevated levels of PINK1, Parkin, LC3BII, and P62 compared to ATR-treated mice. Moreover, Cur mitigates the mitochondrial apoptotic pathway, indicated by the down-regulation of apoptosis-related genes (Cytochrome C (Cyto-C), Caspase3, Caspase9) and the pro-apoptotic marker (Bax), along with the up-regulation of the anti-apoptotic marker (Bcl-2) at both transcriptional and translational levels compared to ATR-treated mice. In summary, Cur demonstrates nephroprotective properties against ATR-induced injury through the enhancement of mitochondrial autophagy and display of anti-apoptotic actions, underscoring its curative potency as a treatment for nephrotoxicity caused by ATR.

Keywords

• Pesticide residues
• Herbal extracts
• Oxidative stress
• Autophagy
• Apoptosis
• Kidney injury