Protective effects of the angiotensin II receptor blocker losartan on cisplatin-induced kidney injury.
BACKGROUND
In the present study, we investigated the possible modulatory effect of losartan, an angiotensin receptor blocker, on oxidative stress induced by cisplatin (CDDP) as well as on CDDP uptake by the kidney.


METHODS
Rats were injected with a single dose of CDDP (7 mg/kg) and/or losartan (in either a single dose of 60 mg/kg or divided doses (10 mg/kg daily for 6 days), starting 1 h before CDDP injection. In addition, rat renal cortical slices were incubated with CDDP (2 mM) and/or losartan (2 mM) for 4 h. Nephrotoxicity was evaluated by measuring serum creatinine and blood urea nitrogen (BUN) in vivo and lactate dehydrogenase (LDH) leakage in vitro; histopathological examination of kidney tissue was also done. Oxidative stress markers including reduced glutathione (GSH) and lipid peroxides were also assessed. Furthermore, CDDP uptake by renal cortical slices was determined.


RESULTS
Losartan has protective effects against CDDP-induced nephrotoxicity as evidenced by restoration of normal serum levels of creatinine and BUN, and LDH leakage. Histopathological examination of the kidney confirmed these results. Also, losartan significantly counteracted CDDP-induced lipid peroxidation and GSH depletion. However, losartan did not affect CDDP uptake by the kidney.


CONCLUSIONS
Our results indicate that losartan has proved to be a promising drug for clinical use as a nephroprotectant against CDDP-induced nephrotoxicity.
Saleh
Samira
S
Department of Pharmacology and Toxicology, Faculties of Pharmacy, University of Cairo, Cairo, Egypt.
Ain-Shoka
Afaf A
AA
El-Demerdash
Ebtehal
E
Khalef
Marwa M
MM
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
D047228:Angiotensin II Type 1 Receptor Blockers; D000970:Antineoplastic Agents; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019808:Losartan; D002945:Cisplatin