Lack of sexual dimorphism in alcohol-induced liver damage (ALD) in rats treated chronically with ethanol-containing low carbohydrate diets: The role of ethanol metabolism and endotoxin.
Evidence has been presented suggesting that females are significantly more susceptible to alcohol-induced liver damage (ALD) than males. In the current study, we examined sexual dimorphism in hepatic pathology, metabolism and cytokine profiles using two different rat models of ALD. Male and female Sprague-Dawley or Wistar rats were fed ethanol-containing low-carbohydrate liquid diets using oral or intragastric methods for 42 or 60 days. In both models, ethanol treatment produced similar significant liver hyperplasia accompanied by increases in plasma ALT, steatosis, inflammation and necrosis (p < 0.05). Greater pathology scores were observed in the intragastrically infused rats. Males did not differ significantly from females in serum ALT values or pathology despite greater elevations in TNFalpha and IL-1beta mRNAs in ethanol-treated female rat livers (p < 0.05). Furthermore, there was no sexual dimorphism in blood ethanol concentrations or CYP2E1-induction even though sexually dimorphic alterations in other hepatic cytochrome P450 enzymes were observed. These data do not support previous observations that female rats have a greater susceptibility to ethanol-induced hepatotoxicity than males.
Ronis
Martin J J
MJ
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. RonisMartinJ@uams.edu
Korourian
Soheila
S
Yoon
Seokjoo
S
Ingelman-Sundberg
Magnus
M
Albano
Emanuele
E
Lindros
Kai O
KO
Badger
Thomas M
TM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002241:Carbohydrates / Q000172:deficiency*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004731:Endotoxins / Q000097:blood*; D004790:Enzyme Induction; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006965:Hyperplasia; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012727:Sex Characteristics; D013045:Species Specificity
D002241:Carbohydrates; D016207:Cytokines; D004040:Dietary Carbohydrates; D004731:Endotoxins; D005609:Free Radicals; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase