title: Oxidative stress induced in rat liver by anticancer drugs doxorubicin, paclitaxel and docetaxel.
abstract: OBJECTIVE
  Oxidative stress generated by anticancer drugs in non-targeted tissues, is considered as a significant factor responsible for their severe side effects, e.g. cardiotoxicity, neurotoxicity and hepatotoxicity. Lack of data on the effect of concurrent administration of commonly used anticancer drugs: doxorubicin (DOX), paclitaxel (PTX) and docetaxel (DTX) on normal tissue, prompted us to examine the markers of oxidative stress in the liver of rats treated with these drugs.
  
  
  METHODS
  Male Wistar rats of average weight 200 g were injected intraperitoneally (i.p.) with 10 mg/kg of body weight (b.w.) of DOX, PTX and DTX. The drugs were given alone or in combinations DOX+taxane. The activities of superoxide dismutase (SOD), catalase (CAT), low molecular weight and total thiols and thiobarbituric acid-reactive substances (TBARS) were estimated.
  
  
  RESULTS
  Combination of two drugs generated greater changes than single agents. Concurrent administration of DOX and PTX increased SOD activity and TBARS, decreased the amount of low molecular weight and total thiols, but did not cause any changes in the activity of catalase. Combination of DOX and DTX induced similar changes except for the activity of catalase, which decreased after the treatment. Of the three drugs only DTX significantly decreased the activity of SOD. However, both taxanes increased the activity of catalase. Although a decrease in concentration of -SH groups, depletion of glutathione and an increase of TBARS were observed after treatment with single drugs, the changes were not statistically significant.
  
  
  CONCLUSIONS
  Concurrent administration of DOX and taxane induced enhanced oxidative stress in comparison to single drugs, which suggests their synergistic prooxidant mode of action in liver.
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. annap@biol.uni.lodz.pl
authors.forename: A
authors.initials: A
authors.lastname: Pieniążek
authors.forename: J
authors.initials: J
authors.lastname: Czepas
authors.forename: J
authors.initials: J
authors.lastname: Piasecka-Zelga
authors.forename: K
authors.initials: K
authors.lastname: Gwoździński
authors.forename: A
authors.initials: A
authors.lastname: Koceva-Chyła
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D018384:Oxidative Stress; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D013438:Sulfhydryl Compounds; D043823:Taxoids; D017392:Thiobarbituric Acid Reactive Substances; D000077143:Docetaxel; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase; D017239:Paclitaxel