Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a g...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2014-10, Vol.280 (2), p.216-223
Main Authors: Aburto, Andrés, Barría, Agustín, Cárdenas, Areli, Carpio, Daniel, Figueroa, Carlos D., Burgos, Maria E., Ardiles, Leopoldo
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Acute Kidney Injury - chemically induced
ANIMAL TISSUES
Animals
Antineoplastic agents
Antineoplastic Agents - toxicity
APOPTOSIS
Biological and medical sciences
Cell Adhesion Molecules - analysis
Chemotherapy
Cisplatin
Cisplatin - toxicity
DIET
EXCRETION
INJURIES
INTRAPERITONEAL INJECTION
KALLIKREIN
Kallikreins - physiology
Kidney - drug effects
KIDNEYS
Male
Malondialdehyde - urine
Medical sciences
Nephrotoxicity
OXIDATION
Oxidative stress
Pharmacology. Drug treatments
POTASSIUM
RATS
Rats, Sprague-Dawley
STIMULATION
Superoxide Dismutase - metabolism
Superoxide Dismutase-1
TOXICITY
Toxicology
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Summary:Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. [Display omitted] •Mechanisms of cisplatin-induced-renal damage have not been completely clarified.•Cisplatin induces oxidative stress and apoptosis.•The renal kallikrein-kinin system is protective in experimental acute renal damage.•Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin.•Protection of the kallikrein-kinin system may reduce cisplatin toxicity.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2014.07.023