Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats.
BACKGROUND
Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. Ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models.


OBJECTIVE
To analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity.


METHODS
Male Sprague-Dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase.


RESULTS
Ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. These protective effects of ozone were dose dependent.


CONCLUSIONS
Intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.
Borrego
Aluet
A
Department of Biomedicine, Ozone Research Center, National Center for Scientific Research, P.O. Box 6414 Havana City, Cuba. ozono@infomed.sld.cu
Zamora
Zullyt B
ZB
González
Ricardo
R
Romay
Cheyla
C
Menéndez
Silvia
S
Hernández
Frank
F
Montero
Teresita
T
Rojas
Enys
E
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D010126:Ozone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000970:Antineoplastic Agents; D017392:Thiobarbituric Acid Reactive Substances; D010126:Ozone; D003404:Creatinine; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin