Protective effect of a mixture of Aloe vera and Silybum marianum against carbon tetrachloride-induced acute hepatotoxicity and liver fibrosis.
The hepatoprotective effects of ACTIValoe N-931 complex, a mixture of Aloe vera and Silybum marianum, against acute and chronic carbon tetrachloride (CCl(4))-induced liver injuries were investigated. Acute hepatotoxicity was induced by intraperitoneal injection of CCl(4) (50 microl/kg), and ACTIValoe N-931 complex at 85, 170, and 340 mg/kg was administered orally 48, 24, and 2 h before and 6 h after injection of CCl(4). Hepatotoxicity was assessed 24 h after CCl(4) treatment. Liver fibrosis was induced by intraperitoneal injection of CCl(4) for 8 weeks (0.5 ml/kg, twice per week), and mice were treated with ACTIValoe N-931 complex at 85, 170, or 340 mg/kg once a day (p.o.). In both acute hepatotoxicity and liver fibrosis, serum aminotransferase levels and lipid peroxidation were increased and the hepatic glutathione content was decreased. These changes were prevented by ACTIValoe N-931 complex. The ACTIValoe N-931 complex attenuated the increase in tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), mRNA expressions in acute hepatotoxicity. In antifibrotic experiments, tissue inhibitor of metalloprotease-1 (TIMP-1) mRNA expression was attenuated by treatment with ACTIValoe N-931 complex. The ACTIValoe N-931 complex decreased the hepatic hydroxyproline content and the transforming growth factor-beta1 levels. Our results suggest that the ACTIValoe N-931 complex has hepatoprotective effects in both acute and chronic liver injuries induced by CCl(4).
Kim
Sung-Hwa
SH
College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea.
Cheon
Ho Jun
HJ
Yun
Nari
N
Oh
Sun-Tack
ST
Shin
Eunju
E
Shim
Kyu Suk
KS
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000504:Aloe / Q000737:chemistry*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D045424:Complex Mixtures / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D020944:Silybum marianum / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D045424:Complex Mixtures; D004338:Drug Combinations; D010936:Plant Extracts; D020011:Protective Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D006909:Hydroxyproline