Iron overload-induced rat liver injury: Involvement of protein tyrosine nitration and the effect of baicalin.
Baicalin has been reported to protect against liver injury in iron-overload mice, however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In this study, we systematically studied the protective effect of baicalin on iron overload induced liver injury, as well as the underlying mechanism based on nitrative stress in rat model. We found that when iron overload rats (500mgiron/kg) were fed baicalin-containing diet (0.3% and 1% w/w) for 45days, baicalin dose dependently protected against iron overload induced liver injury, including alleviation of hepatic pathological damage, decrease of SOD activity, iron content, carbonyl content, and the thiobarbituric acid-reactive substances level in hepatic tissues. It also increased serum iron content, SH content and GPx activity, decreased serum ALT and AST activities. Immunohistochemistry and immunoprecipitation analysis revealed that baicalin could also inhibit iron overload induced protein tyrosine nitration in liver. Moreover, in iron overload rat liver, we found that baicalin decreased the iron overload increased level of glutathione-S-transferases (GSTs) expression, oxidation and nitration. These results suggest that not only oxidative stress, but also nitrative stress, is involved in iron overload induced liver injury, and the underlying mechanism might partially relate to the involvement of GSTs expression and post-translational modification. Baicalin can effectively prevent iron overload caused abnormality and can be a candidate medicine for iron overload diseases.
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China.
Yan
Y
Zhang
Yi
Y
Huang
Xiaorong
X
Deng
Yan
Y
Xu
Zhonghong
Z
Gao
Hailing
H
Li
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology*; D005419:Flavonoids / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism* / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D015538:Nitrosation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D005419:Flavonoids; D017392:Thiobarbituric Acid Reactive Substances; C038044:baicalin; D014443:Tyrosine; D007501:Iron; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase