[Show abstract][Hide abstract] ABSTRACT: to investigate the role of nitric oxide (NO) in ischaemia-reperfusion (I/R) injury in a renal transplant rat model, as I/R injury is a common consequence of renal transplantation and NO has many protective properties that might protect the kidney after I/R injury.
in all, 30 male Sprague-Dawley rats weighing 350-400 g and aged 4-6 months underwent renal transplantation and received FK506 (an immunosuppressant) to overcome early acute rejection episodes. The rats were divided randomly into three groups (10 rats each): Group I, treated with FK506 (2 mg/kg body weight [bw], once daily), served as the control group; Group II, treated with FK506 2 mg/kg bw and L-arginine 300 mg/kg bw; and Group III, treated with FK506 (2 mg/kg bw) and, n-omega-nitro-l-arginine methyl ester (L-NAME; 50 mg/kg bw). Urine and blood samples were taken at 0 (before operation), 2, 7, and 14 days after transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium, and blood urea nitrogen (BUN). Kidney specimens were taken for histological examination by light microscopy.
serum creatinine and BUN levels significantly decreased in the L-arginine-treated group (both P < 0.001) while they were significantly increased in the L-NAME-treated group (P < 0.005 and P < 0.001, respectively) compared with the control group at all time intervals. Light microscopic examination of the renal biopsies in the control group showed acute tubular necrosis, which was minimal in kidneys transplanted and treated with L-arginine and more markedly with L-NAME.
I/R injury impaired graft function during the first week after transplantation. Injection of L-arginine before ischaemia antagonized graft deterioration and improved morphological appearance.
Full-text · Article · Oct 2010 · BJU International
[Show abstract][Hide abstract] ABSTRACT: The aim of this work is to study the safety and the effect of addition of ketoconazole to experimental kidney transplanted rat treated with tacrolimus and predicts the percentage of tacrolimus dose reduction.
The material of this work included 60 male Sprague Dawely rats subjected to renal allotransplantation. They were equally divided into five groups: Group I: served as control group, Group II: received FK506 3.2 mg/kg/bw, Group III: received FK506 2 mg/kg/bw, Group IV: received FK506 1 mg/kg/bw, Group V: received FK506 1 mg/kg/bw plus Ketoconazole 20 mg/kg/day. FK506 trough level and laboratory investigations were determined at 0, 3, 7, 10, 14, and 27 days post-transplantation.
In all groups loss of body weight was observed at day 27 after treatment compared to that before transplantation. Serum creatinine significantly increased at day 27 compared to the basal level in groups treated with 1.0 and 3.2 mg FK506 (1.80 +/- 0.50 versus 0.39 +/- 0.06 P = 0.001) and (1.03 +/- 0.26 versus 0.50 +/- 0.07 P = 0.001) respectively, while for 2.0 mg or 1.0 mg plus keto groups, no significant differences in serum creatinine levels over time (0.56 +/- 0.22 versus 0.44 +/- 0.10 P = 0.106) and (0.55 +/- 0.30 versus 0.42 +/- 0.08 P=0.160) were observed.
Concomitant administration of Ketoconazole and FK506 in transplanted rat model is safe and results in increase of blood trough level concentration of FK506 with 50% reduction of its dose.
No preview · Article · Feb 2005 · International Urology and Nephrology