Rossicaside B protects against carbon tetrachloride-induced hepatotoxicity in mice.
The protective effect of rossicaside B, the major phenylpropanoid glycoside from Boschniakia rossica, on CCl(4)-induced hepatotoxicity and the mechanisms underlying its protective effect were investigated. The mice were administered orally with rossicaside B (100 or 200 mg/kg of body weight) 48, 24 and 1 hr before CCl(4) (0.5 ml/kg of body weight) administration. The CCl(4) challenge caused a marked increase in the levels of serum aspartate aminotransferase, alanine aminotransferase and of tumour necrosis factor-alpha, and propagated lipid peroxidation with a concomitant reduction in reduced glutathione (GSH) and antioxidative enzyme activities in the liver. The administration of rossicaside B to CCl(4)-treated mice not only decreased the serum toxicity marker enzymes and TNF-alpha but also reduced hepatic oxidative stress, as demonstrated by decreased lipid hydroperoxide and thiobarbituric acid-reactive substance concentrations, combined with elevated GSH content and antioxidative enzyme activities in the liver tissues. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and haem oxygenase-1 (HO-1) were elevated after CCl(4) treatment while the cytochrome P450 2E1 (CYP2E1)-specific monooxygenase activity was suppressed. Rossicaside B treatment inhibited the formation of liver nitrite, reduced the over-expression of iNOS and COX-2 proteins, but increased the CYP2E1 function compared with the CCl(4)-treated mice. However, the protein expression of HO-1 was further elevated by rossicaside B treatment. The results demonstrate that rossicaside B provides a protective action on CCl(4)-induced acute hepatic injury, which may be related to its antioxidative activity, suppressed inflammatory responses, induced HO-1 expression and improved CYP2E1 function in the liver.
Department of Biochemistry and Molecular Biology, Medical College of Yanbian University, Yanji, China.
Jishu
J
Quan
Long
L
Piao
Xia
X
Wang
Tian
T
Li
Xuezhe
X
Yin
D000818:Animals; D002109:Caffeic Acids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004187:Disaccharides / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009573:Nitrites / Q000378:metabolism; D031670:Orobanchaceae / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D002109:Caffeic Acids; D004187:Disaccharides; D008054:Lipid Peroxides; D009573:Nitrites; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C547390:rossicaside B; D002251:Carbon Tetrachloride; D010088:Oxidoreductases; D005978:Glutathione