title: Modulatory effects of L-carnitine on tamoxifen toxicity and oncolytic activity: in vivo study.
abstract: The aim of this study was to investigate the protective effect of L-carnitine (L-CAR) in tamoxifen (TAM)-induced toxicity and antitumor activity. Adult female rats were randomly divided into four groups. Group I was served as control, groups II and III were treated with TAM (10 mg/kg, periorally) and L-CAR (300 mg/kg, intraperitoneally), respectively, while group IV was treated with both compounds. The treatment continued daily for 28 days. Administration of TAM resulted in significant increase in serum lipid profiles, liver enzymes, and bilirubin level. TAM produced a significant increase in lipid peroxides (LPO) level and nonsignificant change in nitrogen oxide (NO(x)) level accompanied with significant decrease in superoxide dismutase (SOD) activity of hepatic and uterus tissues and significant decrease in glutathione (GSH) content of uterus tissue. Administration of L-CAR for 1 h prior to TAM treatment decreased serum lipids and liver enzymes significantly and significantly increased SOD activity in liver and uterus tissues compared with TAM-treated group. Furthermore, it restored LPO and GSH levels and increased NO(x) level in uterus tissue. DNA fragmentation and the apoptotic marker, caspase-3, were not detected in the liver of all treated groups. Histopathologically, alterations in the liver and uterus structures after TAM treatment, which was attenuated after L-CAR administration. The antitumor effect and survival of the combined treatment of Ehrlich ascites carcinoma (EAC)-bearing mice was less than each one alone. L-CAR interestingly increased survival rate of EAC-bearing mice more than TAM-treated group. In conclusion, L-CAR has beneficial effects regarding TAM toxicity; however, it interferes with its antitumor effect.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Zawia University, Libya.
authors.forename: A B
authors.initials: AB
authors.lastname: Ibrahim
authors.affiliation: Department of Health Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
authors.forename: H H
authors.initials: HH
authors.lastname: Mansour
authors.affiliation: Department of Cancer Biology, Pharmacology unit, National Cancer Institute, Cairo University, Egypt samiasshouman@yahoo.com.
authors.forename: S A
authors.initials: SA
authors.lastname: Shouman
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Egypt.
authors.forename: A A
authors.initials: AA
authors.lastname: Eissa
authors.affiliation: Department of Health Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt.
authors.forename: S M
authors.initials: SM
authors.lastname: Abu El Nour
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002331:Carnitine / Q000494:pharmacology*; D053938:DNA Fragmentation; D004347:Drug Interactions; D005260:Female; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009589:Nitrogen Oxides / Q000378:metabolism; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology* / Q000633:toxicity*; D014599:Uterus / Q000187:drug effects
chemical_list: D008054:Lipid Peroxides; D009589:Nitrogen Oxides; D013629:Tamoxifen; D013482:Superoxide Dismutase; D002331:Carnitine
keywords:   l-carnitine; Tamoxifen; antioxidants; antitumor activity; organ toxicity