Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations.
BACKGROUND
Despite of the wide spectrum of alcoholism experimental models, the majority of them are very specialized on the short list of investigated parameters and could not provide reproduction of complex metabolic changes in the rats. The aim of the present study was to estimate whether rats selected by high alcohol preference, allowed free access to 15% alcohol for 150 days, develop simultaneous multilevel disturbances of cell macromolecules structure, metabolism and oxidative/nitrosative stress.


METHODS
Wistar albino male rats were divided into groups: I - rats selected by preferences to alcohol were used for chronic alcoholism modeling by replacing water with 15% ethanol (150 days), II - control. Contents of amino acids in serum, liver mRNA CYP2E1 and CYP3A2 expression, DNA fragmentation and lipid peroxidation levels, the reduced glutathione content, superoxide dismutase, catalase, iNOS and cNOS activities were evaluated.


RESULTS
In serum of ethanol-treated rats contents of aspartic acid, serine, glycine, alanine and valine were decreased whereas contents of histidine, methionine and phenylalanine were increased. Liver CYP2E1, CYP3A2 mRNA expression, DNA fragmentation levels significantly elevated. Level of cNOS in ethanol-treated rat's hepatocytes was within the normal limits, whereas iNOS activity was raised 1.6 times. Liver pro- and anti-oxidant system alterations were shown.


CONCLUSIONS
Rats' chronic 15% alcohol consumption (150 days) led solely to complex metabolomic changes at different levels, which simultaneously characterized cell macromolecules structure, metabolism, and oxidative/nitrosative stress. Rodent model of chronic alcoholism in the proposed modification could be an adequate and reasonably priced tool for further preclinical development and testing of pharmacotherapeutic agents.
Ganna M
GM
Shayakhmetova
Larysa B
LB
Bondarenko
Valentina M
VM
Kovalenko
Olga I
OI
Kharchenko
Larisa I
LI
Bohun
Yuliya O
YO
Omelchenko
D000428:Alcohol Drinking / Q000009:adverse effects; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects*; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D019392:Cytochrome P-450 CYP2E1; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A