ABSTRACT
A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.
ABSTRACT
Background: Chronic alcohol consumption gives rise to various health risks that include liver disease, heart disease, pancreatitis, central nervous system disorders and certain forms of cancer. Alcoholic liver disease (ALD) is a spectrum of clinicopathological abnormalities, reflecting an acute or chronic inflammation of the liver parenchyma induced by alcohol use. It is associated with changes in various biochemical parameters and also various clinical manifestations in the patients. The objective of the present study to evaluate clinical and biochemical profile of acute alcoholic liver disease.Methods: The prospective hospital-based case control study was done at MNR Medical College, in the department of General Medicine for duration of one year from March 2017 to April 2018. A total of 120 cases diagnosed clinically and biochemically as Acute alcoholic liver disease were included in the study.Results: The age group ranged from 20 to 60 years and the male to female ratio was 2.42. Majority of the patients were in the age group of 30-40 years (54.1%). Majority of the patients (66.6%) consumed >60 grams/24hours of alcohol. Jaundice, nausea and vomiting were seen in 83.3% cases followed by hepatomegaly in 66.6% cases. Majority of them had been consuming alcohol for more than 5 years.Conclusions: Chronic alcohol consumption is more common in adult males. Chronic alcoholics consume more amount of alcohol. Alcoholic liver disease has a varied clinical presentation and is associated with deranged biochemical parameters.
ABSTRACT
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
ABSTRACT
Alcoholic liver disease (ALD) is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR) and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a) and PPARα (peroxisome proliferator-activated receptor alpha) in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.