title: Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats.
abstract: OBJECTIVE
  Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats.
  
  
  METHODS
  Rats were treated with CAR (250 mg kg(-1) day(-1); intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities.
  
  
  RESULTS
  DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues.
  
  
  CONCLUSIONS
  Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes.
authors.affiliation: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Kumral
authors.affiliation: Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Giriş
authors.affiliation: Oncology Institute, Department of Pathology, Istanbul University, Istanbul, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Soluk-Tekkeşin
authors.affiliation: Oncology Institute, Department of Pathology, Istanbul University, Istanbul, Turkey.
authors.forename: V
authors.initials: V
authors.lastname: Olgaç
authors.affiliation: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Doğru-Abbasoğlu
authors.affiliation: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Ü
authors.initials: Ü
authors.lastname: Türkoğlu
authors.affiliation: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey m.mujdatuysal@hotmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Uysal
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000633:toxicity*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002336:Carnosine / Q000008:administration & dosage / Q000494:pharmacology*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000633:toxicity*; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D019210:Troponin I; D014810:Vitamin E; D004317:Doxorubicin; D002336:Carnosine
keywords: Doxorubicin toxicity; carnosine; oxidative stress; tissues; vitamin E