Angiotensin II type 1 receptor antagonist prevents hepatic carcinoma in rats with nonalcoholic steatohepatitis.

Abstract

BACKGROUND:

Angiotensin II type 1 receptor blockers (ARBs) have been reported to attenuate hepatic fibrosis in non-alcoholic steatohepatitis (NASH). However, it is uncertain whether ARBs prevent hepatocarcinogenesis in NASH even after hepatic fibrosis has developed.

METHODS:

Male Wistar rats were fed with a choline-deficient, L-amino acid-defined (CDAA) diet for 24 weeks, and then fed with the CDAA diet with telmisartan (2 mg/kg/day), a novel ARB, or vehicle for another 24 weeks. The liver histology and the expression of genes and proteins related to angiogenesis were investigated.

RESULTS:

The 24-week CDAA diet induced liver cirrhosis. The 48-week CDAA diet exacerbated liver cirrhosis, and developed hepatocellular carcinoma (HCC) in 54.6 % of the rats concurrently with increases of hypoxia-inducible factor-1α (HIF-1α) protein and vascular endothelial growth factor (VEGF) mRNA, which are potent angiogenic factors in the liver. Telmisartan inhibited hepatic fibrosis and preneoplastic lesions and prevented the development of HCC along with inducing decreases in HIF-1α protein and VEGF mRNA.

CONCLUSIONS:

These data indicated that telmisartan may prevent hepatocarcinogenesis through the inhibition of hepatic angiogenesis even after liver cirrhosis has been established.

• Authors: Yosui Tamaki, Yukiomi Nakade, Taeko Yamauchi, Yuichi Makino, Shiro Yokohama, Mitsuyoshi Okada, Kazunobu Aso, Hiroyuki Kanamori, Tomohiko Ohashi, Ken Sato, Haruhisa Nakao, Masakazu Haneda, Masashi Yoneda
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 48 Issue 4 Pg. 491-503 (Apr 2013) ISSN: 1435-5922 [Electronic] Japan
• PMID: 22886508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Angiotensin II Type 1 Receptor Blockers
• Anticarcinogenic Agents
• Benzimidazoles
• Benzoates
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Telmisartan

Topics

• Amino Acids (administration & dosage)
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Animals
• Anticarcinogenic Agents (therapeutic use)
• Benzimidazoles (therapeutic use)
• Benzoates (therapeutic use)
• Carcinoma, Hepatocellular (etiology, prevention & control)
• Cell Transformation, Neoplastic (drug effects)
• Choline Deficiency (complications)
• Diet (adverse effects)
• Drug Evaluation, Preclinical (methods)
• Fatty Liver (complications, drug therapy, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis, genetics)
• Liver (blood supply)
• Liver Cirrhosis (complications, drug therapy, metabolism, pathology)
• Liver Neoplasms, Experimental (etiology, prevention & control)
• Male
• Neovascularization, Pathologic (etiology, prevention & control)
• Non-alcoholic Fatty Liver Disease
• Rats
• Rats, Wistar
• Telmisartan
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)