Author/Authors :
Ashrafi, Farzaneh epartment of Internal Medicine, School of Medicine - and Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences , Talebi, Ardeshir Kidney Basic Sciences Research Center - and Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences , Nasri, Hamid Kidney Diseases Research Center - and Department of Internal Medicine - School of Medicine, Isfahan University of Medical Sciences , Nematbakhsh, Mehdi Kidney Basic Sciences Research Center - and Department of Physiology - School of Medicine - and Kidney diseases Research Center, Isfahan University of Medical Sciences , Eshraghi-Jazi, Fatemeh Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences , Haghighi, Maryam Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences , Pezeshki, Zahra Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences , Safari, Tahereh Kidney Basic Sciences Research Center, Isfahan University of Medical Sciences
Abstract :
BACKGROUND: Cisplatin (CP) as a potential drug for solid tumors produces nephrotoxicity and disturbs endothelial
function. CP induced nephrotoxicity may be gender related. Nitric oxide plays a pivotal role in endothelial function and
L-arginine as endogenous NO donor promotes endothelial function. The role of L-arginine in CP induced nephrotoxicity
model and its gender related was investigated in this study.
METHODS: Thirty three Wistar rats were randomly assigned to four groups. The groups 1 (male, n = 6) and 2 (female,
n = 11) received a single dose of L-arginine (300 mg/kg, ip), and the day after, they received a single dose of CP
(7 mg/kg). The group 3 (male, n = 9) and 4 (female, n = 7) were assigned to the same regimen except for saline instead
of L-arginine. All animals were sacrificed one week after CP administration. The levels of blood urea nitrogen (BUN),
creatinine and nitrite were measured. The kidneys were also removed for pathological investigations.
RESULTS: Five animals died. All CP treated animals lost weight. The normalized weigh loss was significantly different
between male and female in CP+L-arginine treated animals (p < 0.05). BUN and creatinine were increased significantly
in male treated with CP and in female treated with CP+L-arginine (p < 0.05). L-arginine reduced BUN in male (not in
female) when compared with control groups (p < 0.05). The level of nitrite was increased significantly in L-arginine
treated animals. Kidney tissue damage score and normalized kidney weight were greater in females treated with CP+
L-arginine than female received CP alone (p < 0.05).
Keywords :
Gender , L-arginine , Cisplatin , Nephrotoxicity , Rat