Astaxanthin ameliorates necroptosis through bisphenol-A exposure by regulating brain RIPK1/FADD/RIPK3/MLKL pathway in adult male rats

Bisphenol A (BPA), a common endocrine-disrupting chemical, can cause oxidative damage, apoptosis, and necroptosis in various organs. However, the underlying mechanisms for BPA-induced neurotoxicity were not properly reported. Here, we have evaluated the possible ameliorative roles of astaxanthin (ASX) against BPA-induced brain apoptosis/necroptosis in male rats. Forty male rats were equally grouped (30 days) into control, ASX (75 mg/kg), BPA (50 mg/kg), and BPA/ASX (50 mg/kg/BAP+75 mg/kg/ASX). The present findings demonstrated that ASX could mitigate the diminished acetylcholinesterase (AchE) activity and the increased dopamine, serotonin, and norepinephrine levels, besides anxiety behaviors that resulted from BPA intoxication. Furthermore, ASX significantly reduced BPA-induced brain oxidative injury by mitigating malondialdehyde (MDA), glutathione (GSH), glutathione transferase (GST), superoxide dismutase (SOD), and catalase (CAT) levels. Moreover, ASX could alleviate the histopathological changes promoted by BPA and repair the transcript levels of p53, BcL2, caspase9, FADD, RIPK1/3, MLKL along with Bax, and caspase3 immunoreactivity. In conclusion, ASX reserved brain injury-induced apoptosis, and necroptosis following exposure to BPA through p53/Bcl2/Bax/caspase9/capasase3 and RIPK1/FADD/RIPK3/MLKL pathways.