Heme oxygenase-1 upregulated by Ginkgo biloba extract: potential protection against ethanol-induced oxidative liver damage.
Oxidative stress plays a pivotal role in the pathogenesis and progression of alcoholic liver disease (ALD) and HO-1 induction is suggested to protect hepatocytes from ethanol hepatotoxicity. Here, we present the data to explore the hepatoprotective effect and underlying mechanism(s) of Ginkgo biloba extract (EGB), a naturally occurring HO-1 inducer, against ethanol-induced oxidative damage. Ethanol-fed (2.4 g/kg) male rats were pretreated by EGB (48 or 96 mg/kg) for 90 days. Liver damage was evaluated by histopathology and serum aminotransferase assay. Hepatic redox parameters were measured by spectrophotometry. Heme oxygenase-1 (HO-1) expression was determined by RT-PCR and flow cytometry on mRNA and protein level, respectively. Our results showed that EGB, especially at high dose, ameliorated ethanol-induced macrovesicular steatosis and parenchymatous degeneration in hepatocytes, and decreased serum aminotransferases level. Furthermore, EGB reduced ethanol-derived glutathione depletion and lipid peroxidation, and inhibited the inactivation of superoxide dismutase, glutathione peroxidase and catalase, although EGB itself had no influence on such parameters. Importantly, EGB induced hepatic microsomal HO-1 on mRNA, protein expression and enzymatic activity, which is paralleled to the EGB-derived hepatoprotective effect. Hence, HO-1 upregulation by EGB may enhance the antioxidative capacity against the ethanol-induced oxidative stress and maintain the cellular redox balance.
Yao
Ping
P
Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, PR China.
Li
Ke
K
Song
Fangfang
F
Zhou
Shaoliang
S
Sun
Xiufa
X
Zhang
Xiping
X
Nüssler
Andreas K
AK
Liu
Liegang
L
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002374:Catalase / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity; D005434:Flow Cytometry; D020441:Ginkgo biloba / Q000737:chemistry*; D043384:Glutamyl Aminopeptidase / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D010936:Plant Extracts; D012333:RNA, Messenger; D000431:Ethanol; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D043384:Glutamyl Aminopeptidase; D005978:Glutathione