Uncovering the impact of alcohol on internal organs and reproductive health:Exploring TLR4/NF-kB and CYP2E1/ROS/Nrf2 pathways  

作　　者：Eason Qi Zheng Kong Vetriselvan Subramaniyan Natasha Sura Anak Lubau 

机构地区：[1]Pharmacology Unit,Jeffrey Cheah School of Medicine and Health Sciences,Monash University Malaysia,Subang Jaya,Selangor,Malaysia [2]Center for Global Health Research,Saveetha Medical College,Saveetha Institute of Medical and Technical Sciences,Chennai,Tamil Nadu,India

出　　处：《Animal Models and Experimental Medicine》2024年第4期444-459,共16页动物模型与实验医学（英文）

基　　金：supported by the Jeffrey Cheah School of Medicine and Health Sciences and the Library Resources,Monash University Malaysia

摘　　要：This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health,elucidating the underlying mechanisms involving the Toll-like receptor 4(TLR4)/Nuclear factor kappa light chain enhancer of activated B cells(NF-kB)pathway and the Cytochrome P4502E1(CYP2E1)/reactive oxygen spe-cies(ROS)/nuclear factor erythroid 2-related factor 2(Nrf2)pathways.The TLR4/NF-kB pathway,crucial for inflammatory and immune responses,triggers the production of pro-inflammatory agents and type-1 interferon,disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to al-cohol.Alcohol-induced dysbiosis in gut microbes heightens gut wall permeability to pathogen-associated molecular patterns(PAMPs),leading to liver cell infection and subsequent inflammation.Concurrently,CYP2E1-mediated alcohol metabolism gen-erates ROS,causing oxidative stress and damaging cells,lipids,proteins,and deoxy-ribonucleic acid(DNA).To counteract this inflammatory imbalance,Nrf2 regulates gene expression,inhibiting inflammatory progression and promoting antioxidant re-sponses.Excessive alcohol intake results in elevated liver enzymes(ADH,CYP2E1,and catalase),ROS,NADH,acetaldehyde,and acetate,leading to damage in vital organs such as the heart,brain,and lungs.Moreover,alcohol negatively affects reproduc-tive health by inhibiting the hypothalamic-pituitary-gonadal axis,causing infertility in both men and women.These findings underscore the profound health concerns associated with alcohol-induced damage,emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi-organ im-pacts of alcohol consumption.

关 键 词：ALCOHOL health impact inflammation metabolism molecular pathways 

分 类 号：R163[医药卫生—公共卫生与预防医学]