Exploring the neuroprotective potential of losartan against acrylamide-induced oxidative stress and apoptosis in PC12 cells.

Abstract

Acrylamide (ACR), a potential neurotoxin, is produced during industrial and food processing. The mechanisms of ACR neurotoxicity are still under debate, and effective strategies need to be investigated. We examined the neuroprotective potential of losartan (LOS), an antihypertensive drug, against ACR-induced neurotoxicity. PC12 cells were treated with concentrations of LOS (10, 20, and 50 μM) for 24 h and then exposed to ACR (5 mM) for a further 24 h. Antioxidant markers (SOD and CAT) and oxidative damage markers (ROS and TBARS) were measured. Real-time PCR was used to examine the mRNA expression of Bax and Bcl-2. Western blotting was used to evaluate the protein expression of Nrf2, Keap1, HO-1, as well as total and cleaved caspase-3. Exposure to ACR caused a significant increase in ROS and TBARS levels and reduced activities of SOD and CAT. Exposure to ACR affected the mRNA expression of key apoptotic regulators Bax and Bcl-2, resulting in a higher Bax/Bcl-2 expression. Furthermore, ACR elevated the protein expression of total and cleaved caspase-3 and Nrf2, while decreasing Keap1 levels. ACR-induced changes were reversed by LOS treatment. The findings demonstrated that LOS can protect PC12 cells from ACR-induced neurotoxicity by enhancing antioxidant defenses and modulating apoptotic signaling.

Key Findings

• Acrylamide exposure increased ROS and TBARS levels while reducing SOD and CAT activities in PC12 cells.
• Acrylamide altered apoptotic gene expression by increasing Bax/Bcl-2 ratio and elevating total and cleaved caspase-3 protein levels.
• Losartan treatment reversed acrylamide-induced oxidative stress and apoptotic changes by enhancing antioxidant defenses and modulating Nrf2, Keap1, and HO-1 protein expression.

Clinical Significance

Citation

Molavinia Shahrzad, Shariati Saeedeh, Mohtadi Shokoohet al.. Exploring the neuroprotective potential of losartan against acrylamide-induced oxidative stress and apoptosis in PC12 cells. International journal of environmental health research. 2026-Jun-29.