Evaluation of polyethylene microplastics toxicity using Nrf2/ARE and MAPK/Nrf2 signaling pathways

Microplastics (MPs) have emerged as a serious global environmental threat due to their resistance to degradation and persistence in ecosystems. Given their potential risks to human health, it is essential to thoroughly investigate the mechanisms of toxicity and associated health consequences. This study examined the toxicological and reproductive effects of varying doses of polyethylene microplastics (PE-MPs) in 120 male and female Sprague Dawley rats. A statistically significant, dose-dependent increase in malondialdehyde levels was observed, along with a reduction in catalase activity. Furthermore, alterations were detected in sexual hormone levels and disruptions were noted in both the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-ARE (antioxidant response element) and p38 MAPK-Nrf2 signaling pathways. PE-MP exposure also produced marked histopathological changes in the testes and ovaries. These findings indicate that reproductive toxicity from PE-MPs is associated with impairments in the Keap1-Nrf2-ARE and p38 MAPK-Nrf2 pathways. The results underscore the importance of limiting MP exposure to mitigate potential health hazards and provide new data on the potential mechanisms of toxicity of MPs.