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.