[The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration].
The paracetamol and cyclophosphamid are metabolized in the liver by the cytochrome P450. The formed reactive intermediates are responsible of a hepatocyte depletion of the glutathion and a lipoperoxydation. the vinblastine is also a chemotherapeutic agent hepatotoxic and hematotoxic. Otherwise, flavonoïds are polyphenols substances of plant origin having some biological and anti-oxydative properties. However no information is available on their effects on glutathion and glutathion-s-transferases. In our research, we valued the effect of oral administration of flavonoids (diosmine and quercetine) under shape of propolis extract to 60 mg/kg daily during 14 days, on hematological and hepatic toxicity of a single dose of cyclophosphamide 80 mg/kg by intravenous way, vinblastine 2 mg/kg by intravenous way and the hepatic toxicity of the paracetamol managed by oral way to 200 mg/kg corresponding to 2/3 the DL50 at the rat female albinos wistar. We did a blood numeration, an assessment of serum activities of transaminases and alkali phosphatases as well as quantification of the glutathion and the malondialdehyde (MDA) in liver homogenats of rats treated. Analyses are done at regular intervals; 1, 3, 7 and 14 days after the administration of drugs. In the group of rats treated by the cyclophosphamid paracetamol alone we observed since the 1st day, an increase of lipid peroxide (MDA) of 120% and a downfall of hepatic glutathion including the group receiving the vinblastine (until 210% of reduction). In the same way a severe leucopenia and a thrombopenia (70% of reduction) are observed between the 3rd and the 14th day at rats treated by the chemotherapeutic agents alone (cyclophosphamide and vinblastine). The combination of flavonoids with drugs have clearly reduced the effect of drugs toxicity. Indeed, the aplasic observed with the vinblastine, as well as the leucopenia and thrombopenia of the cyclophosphamide are corrected entirely. In the same way, we noted a restoration of rates of peroxide and glutathion. Flavonoïds seem to act by activation of the turn over of the glutathion and enzymes stimulating particularly glutathion-s-transferases permitting the captation of the reactive metabolites of the studied drugs.
Lahouel
M
M
Laboratoire de pharmacologie et phytochimie, département de biologie, université de Jijel, 18000 Jijel, Algérie. lahouelmesbah@ifrance.com
Boulkour
S
S
Segueni
N
N
Fillastre
J P
JP
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D004145:Diosmin / Q000494:pharmacology; D005260:Female; D044948:Flavonols / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D023421:Models, Animal; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014747:Vinblastine / Q000633:toxicity*
D044948:Flavonols; D000082:Acetaminophen; D008315:Malondialdehyde; D014747:Vinblastine; D004145:Diosmin; D003520:Cyclophosphamide; D011794:Quercetin; D005978:Glutathione