Namachivayam Arunraj, Valsala Gopalakrishnan Abilash
Department of Biomedical Sciences, School of Bio-Sciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, India.
Heliyon. 2023 Oct 21;9(11):e21267. doi: 10.1016/j.heliyon.2023.e21267. eCollection 2023 Nov.
Ethanol (EtOH) is most widely used in alcoholic beverages to prepare alcohol. As EtOH is mainly metabolised in the liver, the excessive consumption of EtOH forms a primary toxic metabolic product called acetaldehyde, as the gradual increase in acetaldehyde leads to liver injury, as reported. Lauric acid (LA) is rich in antioxidant, antifungal, antibacterial, anticancer, and antiviral properties. LA is an edible component highly present in coconut oil. However, no report on LA protective effects against the EtOH-instigated hepatotoxicity exists. Therefore, the experiment is carried out to investigate the potency effects of LA on EtOH-instigated hepatotoxicity in thirty male albino rats. Rats were divided into five groups (n-6): control DMSO alone, EtOH -intoxicated, EtOH + LA 180 mg/kg, EtOH + LA 360 mg/kg, and LA alone were administered orally using oral gavage. The study measured body weight every weekend in all rat groups. The rats were sacrificed and assessed for serum markers (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase), antioxidant activity (superoxide dismutase, reduced glutathione, glutathione peroxidase), lipid peroxidation (malondialdehyde), histopathological, cytokine levels (TNF-α, IL-1β and IL-6), protein expression (caspase 3 and caspase 8 and Bcl-2 and HNF4α) were evaluated after the 56-days study period. The impact of EtOH intoxication reduces the rat's body weight by 90 g, upregulates the liver enzyme markers, depletes the antioxidant levels, produces malondialdehyde, changes the histoarchitecture (periportal inflammation and hepatocyte damage), downregulates the Bcl-2 expressions and HNF4α, and elevates the expression of cytokines and apoptotic markers. LA alleviated EtOH-induced liver toxicity by significant (p < 0.05) modulation of biochemical levels, caspase-8/3 signalling, reducing pro-inflammatory cytokines, and restoring the normal histoarchitecture, upregulating the Bcl-2 and HNF4α Expressions. In conclusion, LA treatment can protect the liver against EtOH-induced hepatotoxicity, evidenced by alleviating Oxidative stress, lipid peroxidation, inflammation, apoptosis, and upregulation of HNF4α.
乙醇（EtOH）在酒精饮料中被广泛用于制备酒精。由于EtOH主要在肝脏中代谢，过量摄入EtOH会形成一种主要的有毒代谢产物乙醛，正如报道的那样，乙醛的逐渐增加会导致肝损伤。月桂酸（LA）具有丰富的抗氧化、抗真菌、抗菌、抗癌和抗病毒特性。LA是椰子油中高度含有的一种可食用成分。然而，目前尚无关于LA对EtOH诱发的肝毒性的保护作用的报道。因此，本实验旨在研究LA对30只雄性白化大鼠EtOH诱发的肝毒性的潜在影响。将大鼠分为五组（n = 6）：单独给予对照二甲基亚砜（DMSO）、EtOH中毒组、EtOH + 180 mg/kg LA组、EtOH + 360 mg/kg LA组和单独给予LA组，通过灌胃法进行口服给药。该研究在每个周末测量所有大鼠组的体重。在为期56天的研究期结束后，处死大鼠并评估血清标志物（碱性磷酸酶、丙氨酸转氨酶、天冬氨酸转氨酶）、抗氧化活性（超氧化物歧化酶、还原型谷胱甘肽、谷胱甘肽过氧化物酶）、脂质过氧化（丙二醛）、组织病理学、细胞因子水平（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6）、蛋白表达（半胱天冬酶3、半胱天冬酶8、Bcl-2和肝细胞核因子4α）。EtOH中毒的影响使大鼠体重减轻90克，上调肝酶标志物，消耗抗氧化剂水平，产生丙二醛，改变组织结构（汇管区炎症和肝细胞损伤），下调Bcl-2表达和肝细胞核因子4α，并升高细胞因子和凋亡标志物的表达。LA通过显著（p < 0.05）调节生化水平、半胱天冬酶-8/3信号传导、减少促炎细胞因子以及恢复正常组织结构、上调Bcl-2和肝细胞核因子4α表达，减轻了EtOH诱导的肝毒性。总之，LA治疗可以保护肝脏免受EtOH诱导的肝毒性，这通过减轻氧化应激、脂质过氧化、炎症、凋亡以及上调肝细胞核因子4α得以证明。
