title: 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.
abstract: 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.
authors.affiliation: National Research Laboratory, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Sillim-dong, Kwanak-gu, Seoul 151-742, South Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Ki
authors.forename: Myong Sok
authors.initials: MS
authors.lastname: Ko
authors.forename: Choon Won
authors.initials: CW
authors.lastname: Kim
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Lee
authors.forename: Young Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
mesh_terms: 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*
chemical_list: 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