Abstract:
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 P450 2E1 (CYP2E1)/reactive oxygen species (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 alcohol. 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 generates ROS, causing oxidative stress and damaging cells, lipids, proteins, and deoxyribonucleic acid (DNA). To counteract this inflammatory imbalance, Nrf2 regulates gene expression, inhibiting inflammatory progression and promoting antioxidant responses. 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 reproductive 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 impacts of alcohol consumption.
摘要:
这篇综述探讨了饮酒对内脏器官和生殖健康的有害影响,阐明涉及活化B细胞的Toll样受体4(TLR4)/核因子κ轻链增强剂(NF-kB)途径和细胞色素P4502E1(CYP2E1)/活性氧(ROS)/核因子红细胞相关因子2(Nrf2)途径的潜在机制。TLR4/NF-kB通路,对于炎症和免疫反应至关重要,引发促炎因子和1型干扰素的产生,当组织长期暴露于酒精时,会破坏炎症和抗氧化反应之间的平衡。酒精诱导的肠道微生物菌群失调会增加肠道壁对病原体相关分子模式(PAMPs)的渗透性,导致肝细胞感染和随后的炎症。同时,CYP2E1介导的酒精代谢产生ROS,引起氧化应激和损伤细胞,脂质,蛋白质,和脱氧核糖核酸(DNA)。为了抵消这种炎症失衡,Nrf2调节基因表达,抑制炎症进程和促进抗氧化反应。过量饮酒会导致肝酶升高(ADH,CYP2E1和过氧化氢酶),ROS,NADH,乙醛,和醋酸盐,导致心脏等重要器官受损,大脑,还有肺.此外,酒精通过抑制下丘脑-垂体-性腺轴来对生殖健康产生负面影响,导致男性和女性不孕。这些发现强调了与酒精引起的损害相关的深刻健康问题,强调需要提高公众对免疫反应和饮酒的多器官影响之间复杂的相互作用的认识。