Effect of the inducer of interleukin-6 (ME3738) on rat liver treated with ethanol.
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.
Fukumura
Atsushi
A
Department of Gastroenterology, Kanazawa Medical University, Ishikawa, Japan.
Tsutsumi
Mikihiro
M
Tsuchishima
Mutsumi
M
Hayashi
Nobuhiko
N
Fukura
Masayuki
M
Yano
Hirokazu
H
Ozaki
Kazuaki
K
Takase
Shujiro
S
D000255:Adenosine Triphosphate / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D005235:Fatty Liver, Alcoholic / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D014280:Triglycerides / Q000097:blood; D005723:gamma-Glutamyltransferase
D015850:Interleukin-6; C477463:ME3738; D014280:Triglycerides; D009828:Oleanolic Acid; D000255:Adenosine Triphosphate; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase