ArticleToxicology and applied pharmacology2013
Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity.
Article in Toxicology and applied pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.Environmental health perspectives · 2022Pooled it
- Blood Trihalomethane Concentrations and Gestational Diabetes Mellitus: A Nationwide Cross-Sectional Study.Current medical science · 2026Article
- Occurrence of halonaphthoquinone disinfection byproducts in Shanghai's drinking water and the hepatotoxic effects on lipid accumulation.Frontiers in public health · 2026Article
- Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study.Environmental health perspectives · 2024Article
- A time differentiated dietary intervention effect on the biomarkers of exposure to pyrethroids and neonicotinoids pesticides.iScience · 2023Article
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- Lipocalin 2 induces neuroinflammation and blood-brain barrier dysfunction through liver-brain axis in murine model of nonalcoholic steatohepatitis.Journal of neuroinflammation · 2020Article
- High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease.Redox biology · 2018Article
- Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress and apoptosis in mice.The Journal of nutritional biochemistry · 2016Article
- Coffee but not green tea consumption is associated with prevalence and severity of hepatic steatosis: the impact on leptin level.European journal of clinical nutrition · 2015Article
- Trihalomethane exposure and biomonitoring for the liver injury indicator, alanine aminotransferase, in the United States population (NHANES 1999-2006).The Science of the total environment · 2015Article
- Alcoholic, Nonalcoholic, and Toxicant-Associated Steatohepatitis: Mechanistic Similarities and Differences.Cellular and molecular gastroenterology and hepatology · 2015Review
- Increased Sensitivity to Binge Alcohol-Induced Gut Leakiness and Inflammatory Liver Disease in HIV Transgenic Rats.PloS one · 2015Article
- M1 polarization bias and subsequent nonalcoholic steatohepatitis progression is attenuated by nitric oxide donor DETA NONOate via inhibition of CYP2E1-induced oxidative stress in obese mice.The Journal of pharmacology and experimental therapeutics · 2015Article
- P2X7 receptor as a key player in oxidative stress-driven cell fate in nonalcoholic steatohepatitis.Oxidative medicine and cellular longevity · 2015Review
- Article
- Plasma adipocytokines and antioxidants-status in Korean overweight and obese females with dyslipidemia.Nutrition research and practice · 2014Article
- CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8+ T cells aid progression of environment-linked nonalcoholic steatohepatitis.Toxicology and applied pharmacology · 2014Article
- Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.