Phytochemical Compounds Attenuate Nonylphenol Induced Oxidative Stress, Liver injury and Estradiol Disruption: Experimental and Molecular Docking Insights

Nonylphenol (NP) is a synthetic xenoestrogen causes sex hormones imbalance and oxidative stress inducer. Resveratrol (RES) and Naringenin (NG) are phytochemicals possessing antioxidant properties and estrogenic activity. This study was conducted to study the toxicity of NP and the mitigating effects of RES and NG on NP toxic impacts in rats. Thirty male rats were classified into 5 groups as follows: 1- Normal control (NC) group, 2- Dimethyl sulfoxide (DMSO) group, 3- NP group, 4- NP+RES and 5- NP+NG. Results revealed that NP treatment significantly decreased the Glutathione (GSH)and sulfhydryl (R-SH) groups content compared to NC group. In addition, significant escalation was observed in the levels of liver functions parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), except total protein level was decreased compared to NC. Besides, lipid profile parameters, total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglycerides exhibited significant increase compared to NC, but high density lipoprotein (HDL) level showed significant reduction. All the recorded effects induced by NP treatment were effectively countered by co-treatment with RES or NG. in addition, molecular docking studies were carried out to investigate the interactions between Estradiol, NP, RES, NG and estrogen receptor alpha which provide a possible mechanism for their potential estrogenic activity. Overall, our study contributes to a deeper understanding of the toxic effect of NP on antioxidant capacity, liver and kidney function, blood composition, regulated lipid levels and estradiol disruption. Besides, it underscores the potential therapeutic utility of RES and NG in alleviating these adverse effects.