RT Journal Article
SR Electronic
T1 Binge alcohol is more injurious to liver in female than male rats: histopathological, pharmacological, and epigenetic profiles.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.119.258871
DO 10.1124/jpet.119.258871
A1 Shivendra D. Shukla
A1 Ricardo J Restrepo
A1 Annayya R Aroor
A1 Xuanyou Liu
A1 Robert W Lim
A1 Jacob D Franke
A1 David A Ford
A1 Ronald J Korthuis
YR 2019
UL http://jpet.aspetjournals.org/content/early/2019/06/28/jpet.119.258871.abstract
AB Binge alcohol consumption is a health problem but differences between sexes remain poorly defined. We have examined the in vivo effects of acute three repeat binge alcohol administration on liver in male and female rats. Sprague-Dawley rats were gavaged with alcohol (5 gm /kg body weight) 3 times at 12 hourly intervals. Blood and liver tissues were collected 4 hours after the last binge ethanol. Subsequently, a number of variables were analyzed. Compared to male, female had higher levels of blood alcohol, alanine aminotransferase, and triglycerides. Liver histology showed increased lipid vesicles with larger sizes in females. Protein levels of liver CYP2E1 were higher in female than male liver after binge. Hepatic phospho-ERK1/2 and phosph-p38MAPK protein levels were lower in female compared to male after binge alcohol with no differences in the phospho-JNK levels. PGC1α and CREB protein levels increased more in female than male liver. However, increases in phospho-CREB levels were lower in females. Remarkably, c-fos was reduced substantially in female liver with no differences in c-myc protein. Binge ethanol caused elevation in acetylated (H3AcK9) and phospho-acetylated (H3AcK9PS10) histone H3 in both sexes but without any difference. Binge alcohol caused differential alterations in the levels of various species of phosphatidylethanol (PEth) and a larger increase in the diacylglycerol kinase-α protein levels in female compared to male livers. These data demonstrate for the first time similarities and differences in the gender-specific responses to repeat binge alcohol leading to the increased susceptibility of female liver to injury in vivo.SIGNIFICANCE STATEMENT This study examines the molecular responses of male and female rat liver to acute binge alcohol in vivo and demonstrates significant differences in the susceptibility between genders.