Garlic oil and DDB, comprised in a pharmaceutical composition for the treatment of patients with viral hepatitis, prevents acute liver injuries potentiated by glutathione deficiency in rats.
A pharmaceutical composition PENNEL comprising garlic oil (GO) and dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) as ingredients active for phase II enzyme induction and liver protection, respectively, has been used as a curative preparation for patients with acute or chronic viral hepatitis. In spite of the wide clinical use of PENNEL in Asian and Middle Eastern countries, whether GO+DDB treatment synergistically protects the liver from injuries potentiated by GSH deficiency compared to the individual treatment has not been determined. This study investigated the effects of GO+DDB in comparison with each ingredient alone on chemical-induced liver injury potentiated by a GSH depleting agent. Rats that had been daily pretreated with GO+DDB, GO, DDB, ursodesoxycholic acid or silymarin for 6 days were exposed to buthionine sulfoximine (BSO) and then injected with a single dose of CCl4. The effects of the agents on acute liver toxicities induced by BSO, CCl4 or BSO+CCl4 were assessed by blood biochemistry and histopathology. GO+DDB pretreatment effectively prevented increases in plasma aminotransferases or lactate dehydrogenase activities in rats exposed to BSO+CCl4, compared to GO or DDB treatment alone. Whereas BSO potentiated CCl4-induced liver injuries as evidenced by elevations in central necrosis, hepatocyte degeneration and inflammation, pretreatment with GO+DDB abrogated BSO+CCl4-induced liver injuries more efficaciously than did that with GO or DDB. The hepatoprotective effect of GO+DDB was superior to that of ursodesoxycholic acid or silymarin. Also, blood biochemistry indicated that GO+DDB pretreatment prevented increases in plasma triglyceride contents in rats insulted with CCl4 or BSO+CCl4. The present study demonstrated that GO+DDB, when daily pretreated for six consecutive days, exerted synergistic protection of the liver from chemical-induced injury potentiated by the condition of GSH deficiency, and has additional advantages in lowering the plasma lipids.
Park
Eun Young
EY
National Research Laboratory, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Sillim-dong, Kwanak-gu, Seoul 151-742, South Korea.
Ki
Sung Hwan
SH
Ko
Myong Sok
MS
Kim
Choon Won
CW
Lee
Min Ho
MH
Lee
Young Sok
YS
Kim
Sang Geon
SG
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000498:Allyl Compounds / Q000627:therapeutic use*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004149:Dioxoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005978:Glutathione / Q000037:antagonists & inhibitors*; D006525:Hepatitis, Viral, Human / Q000188:drug therapy*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000627:therapeutic use*
D000498:Allyl Compounds; D001713:Biphenyl Compounds; D004149:Dioxoles; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D013440:Sulfides; C038491:allyl sulfide; C043146:7-hydroxy-7'-methoxy-4,4'-bis(1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione