Effect of the inducer of interleukin-6 (ME3738) on rat liver treated with ethanol.

Abstract

BACKGROUND:

Recently, ME3738, a derivative of soyasapogenol B, was developed as an inducer of interleukin (IL)-6. It has been demonstrated that ME3738 is stimulate to produce IL-6 and that it protects against concanavalin A-induced liver failure. It has also been reported that IL-6 prevents alcoholic fatty liver in mice. These results suggest that ME3738 may prevent alcoholic liver injury. In the present study, we investigated whether ME3738 prevents fatty liver in ethanol-fed rats.

METHODS:

Twenty-four male rats were fed with liquid diets containing ethanol or carbohydrates for 8 weeks. Liquid diets were prepared with or without ME3738 (0.8 mg/mL). Liver sections were stained for histology and IL-6 expression. Fatty changes of liver were classified into 4 grades: 0, 1+, 2+, and 3+. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), triglyceride, total cholesterol, and IL-6 were measured, as was hepatic ATP content.

RESULTS:

The extent of fatty degeneration in ethanol-fed rats was significantly greater (p=0.023) than that in controls. Fatty changes in rats fed ethanol containing ME3738 decreased, but were not significantly different from those in rats fed ethanol. Immunohistochemical staining of IL-6 was observed in perivenular hepatocytes of all rats, with its intensity becoming stronger in the order of controls, controls containing ME3738, ethanol, and ethanol-containing ME3738-fed rats. Plasma levels of AST and ALT in rats fed ethanol were significantly higher than those in controls. In rats fed ethanol-containing ME3738, these levels decreased to those of control-fed rats, but were not significantly different from those in rats fed ethanol. Plasma IL-6 was not detected in any rats. Hepatic ATP content in rats fed ethanol was significantly (p<0.05) lower than that in control-fed rats; however, in rats fed ethanol-containing ME3738, it increased to that in control-fed rats.

CONCLUSIONS:

Oral administration of ME3738, inducer of IL-6 may prevent the development of fatty liver caused by chronic ethanol consumption.

• Authors: Atsushi Fukumura, Mikihiro Tsutsumi, Mutsumi Tsuchishima, Nobuhiko Hayashi, Masayuki Fukura, Hirokazu Yano, Kazuaki Ozaki, Shujiro Takase
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 31 Issue 1 Suppl Pg. S49-53 (Jan 2007) ISSN: 1530-0277 [Electronic] England
• PMID: 17331166 (Publication Type: Journal Article)

Chemical References

• Interleukin-6
• ME3738
• Triglycerides
• Oleanolic Acid
• Adenosine Triphosphate
• Cholesterol
• gamma-Glutamyltransferase
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• Adenosine Triphosphate (blood)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Cholesterol (blood)
• Fatty Liver, Alcoholic (immunology, pathology, prevention & control)
• Interleukin-6 (metabolism)
• Liver (immunology, pathology)
• Liver Function Tests
• Male
• Oleanolic Acid (analogs & derivatives, pharmacology)
• Rats
• Triglycerides (blood)
• gamma-Glutamyltransferase