Chronic supplementation of creatine and vitamins C and E increases survival and improves biochemical parameters after Doxorubicin treatment in rats.
1. Doxorubicin is an anti-cancer drug with well-described effects against a wide range of tumours. However, doxorubicin also exhibits dose-dependent cytotoxicity. The purpose of the present study was to determine whether chronic supplementation of creatine or a mix of vitamins C and E could increase survival and improve plasma parameters 48 h after doxorubicin treatment. 2. Rats were divided into four groups: (i) saline (control); (ii) doxorubicin treated; (iii) a creatine (0.2 g/kg per day)-supplemented group; and (iv) a vitamin C (250 mg/kg per day) and E (400 IU/kg per day)-supplemented group. After 30 days supplementation of rats with either creatine or the vitamins, one dose of doxorubicin (15 mg/kg, i.p.) was administered. 3. There was no difference in weight loss among the groups until the 3rd day after doxorubicin treatment, but the creatine- and vitamin-supplemented groups lived longer compared with the doxorubicin only treated group (6, 7 and 3 days, respectively). The doxorubicin-treated group lost 13.4% bodyweight over 3 days, whereas the creatine- and vitamin-supplemented groups lost approximately 35% 3 days after the administration of doxorubicin. Doxorubicin treatment resulted in an increase in alanine aminotransferase (ALT; P < 0.05), lactate dehydrogenase (LDH; P < 0.05), urea (P < 0.05) and creatinine (P < 0.05) compared with levels observed in the control group. Conversely, creatine supplementation promoted a partial return to control values for LDH (P < 0.05) and creatinine (P < 0.05), whereas the vitamin mix reversed the changes in ALT (P < 0.05), LDH (P < 0.05), urea (P < 0.05) and creatinine (P < 0.05). 4. In conclusion, the results of the present study indicate that the two supplementation protocols decreased the cytotoxic effects of doxorubicin and that a protective effect was more noticeable in animals supplemented with the mixture of vitamins C and E.
Santos
Ronaldo V T
RV
Laboratory of Metabolism, Institute of Biomedical Sciences, University of São Paulo, and Department of Health Science, Federal University of São Paulo, Baixada Santista, Brazil. rvca@usp.br
Batista
Miguel L
ML
Caperuto
Erico C
EC
Costa Rosa
Luis Fbp
LF
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology*; D003401:Creatine / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D004359:Drug Therapy, Combination; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014508:Urea / Q000097:blood; D014810:Vitamin E / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology; D015431:Weight Loss / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D020011:Protective Agents; D014815:Vitamins; D014810:Vitamin E; D004317:Doxorubicin; D014508:Urea; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D003401:Creatine; D001205:Ascorbic Acid