Antibiotics prevent liver injury in rats following long-term exposure to ethanol
Abstract
Background/aims Kupffer's cells participate in alcohol-induced liver injury, and endotoxemia is observed in human alcoholics and in a rat model. This study evaluated the effect of reducing bacterial endotoxin production by intestinal sterilization on alcohol-induced liver injury.Methods Male Wistar rats were exposed to ethanol continuously for up to 3 weeks via intragastric feeding. The gut was sterilized with polymyxin B and neomycin.Results Fecal culture of stool samples from ethanol-fed rats treated with antibiotics showed virtually no growth of gram-negative bacteria. Endotoxin levels of 80-90 pg/mL in plasma of ethanol-fed rats were reduced to < 25 pg/mL by antibiotics. Antibiotic treatment also completely prevented elevated aspartate aminotransferase levels and significantly reduced the average hepatic pathological score in rats exposed to ethanol. Oxygen tension on the surface of the liver measured in vivo was decreased significantly from control values of 48 +/- 1 to 39 +/- 1 mumol/L in ethanol-treated rats. This hypoxia was prevented by treatment with antibiotics. Moreover, the increase in rates of ethanol elimination due to long-term ethanol treatment was prevented by antibiotic treatment.Conclusions Intestinal sterilization prevented alcohol-induced liver injury in the rat, supporting the idea that hypermetabolism and consequent hypoxia caused by activation of Kupffer's cells by endotoxin is involved in the mechanism.
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Global TLR4 deficiency in mice and gut sterilization with nonabsorbable antibiotics in rats reduce hepatic steatosis, oxidative stress and inflammation.
“Global TLR4 deficiency in mice as well as gut sterilization with nonabsorbable antibiotics in rats reduces hepatic steatosis, oxidative stress and inflammation46–48.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [48]
Murine data show that nonabsorbable antibiotics and norfloxacin improve alcoholic liver disease and insulin resistance in NAFLD.
“As data from murine studies show that non-absorbable antibiotics and norfloxacin improve ALD48,116 and insulin resistance in NAFLD117, they might be particularly attractive for HCC prevention in these patient groups.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [48]
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- Authors
- Adachi, Y., Moore, L. E., Bradford, B. U., Gao, W., & Thurman, R. G.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Moore, Laura E.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 1995-01
- Volume
- 108
- Issue
- 1
- Pages
- 218-224
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2014185375
- Cited by
- 692
- References
- 36
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 17 · 2020: 25 · 2019: 20 · 2018: 29 · 2017: 33 · 2016: 26 · 2015: 36 · 2014: 29 · 2013: 28 · 2012: 30
- FWCI
- 17.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA03624, AA09156, R01AA009156)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- alcohol-induced liver injury, ethanol, polymyxin B, neomycin, endotoxemia, Kupffer cells, hepatic hypoxia, ethanol elimination, Gram-negative bacteria, aspartate aminotransferase, hepatic steatosis
- MeSH terms
- Ethanol, Animals, Anti-Bacterial Agents, Dietary Fats, Endotoxins, Liver, Liver Diseases, Alcoholic, Male, Neomycin, Polymyxin B, Time Factors, Rats, Wistar, Rats
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