Effect of benzophenones from Hypericum annulatum on carbon tetrachloride-induced toxicity in freshly isolated rat hepatocytes.
Five benzophenones and a xanthone, isolated from Hypericum annulatum Moris, were investigated for their protective effect against carbon tetrachloride toxicity in isolated rat hepatocytes. The benzophenones and the xanthone gentisein were administered alone (100 microM) and in combination with CCl4 (86 microM). CCl4 undergoes dehalogenation in the liver endoplasmic reticulum. This process leads to trichlormethyl radical (*CCl3) formation, initiation of lipid peroxidation, and measurable toxic effects on the hepatocytes. The levels of thiobarbituric acid reactive substances (TBARS) were assayed as an index of lipid peroxidation (LPO). Lactate dehydrogenase (LDH) leakage, cell viability and reduced glutathione (GSH) depletion were used as signs of cytotoxicity. CCl4 significantly decreased hepatocyte viability, GSH level and increased TBARS level and LDH leakage as compared to the control. Our data indicate that 2,3',5',6-tetrahydroxy-4-methoxybenzophenone, 2-O-alpha-L-arabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone and 2-O-alpha-L-3'-acetylarabinofuranosyl-3',5',6-trihydroxy-4-methoxybenzophenone showed weaker toxic effects compared to CCl4 and in combination showed statistically significant protection against the toxic agent.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University - Sofia, Sofia, Bulgaria.
Mitka
M
Mitcheva
Magdalena
M
Kondeva
Vessela
V
Vitcheva
Paraskev
P
Nedialkov
Gerassim
G
Kitanov
D000818:Animals; D001577:Benzophenones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D028084:Clusiaceae / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D001577:Benzophenones; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; D044004:Xanthones; C436833:gentisein; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D005978:Glutathione