Antiapoptotic effect of angiotensin-II type-1 receptor blockade in renal tubular cells of hyperoxaluric rats

In this study, we investigated the protective effect of losartan as an AT1 receptor antagonist by evaluating the expression of apoptosis-regulatory genes that contribute to the progressive damage in the renal tubules of hyperoxaluric rats. Rats were divided into 4 groups of 10 each; control (C), ethylene glycol (EG), ethylene glycol + losartan (EG + L) and Losartan (L). For 4 weeks 0.8% EG, as a precursor for oxalate, was administered to EG and EG + L and losartan (300 mg/l) was administered to groups EG + L and L. Urine and blood samples were collected for biochemical determination. Bcl-2, bax, caspase-3 and TGF-beta 1 antibodies were used for immunohisto-chemistry. Apoptosis was determined by TUNEL method. A marked increase in urinary oxalate levels of the rats in EG and EG + L groups was found. In the EG group a diffuse amount of oxalate crystals into the tubular lumina and interstitium in the cortex was observed. In the EG group GBM thickening, interstitial fibrosis and tubular atrophy with infiltration of mononuclear cell findings reduced in the EG + L group were presented as well. In the EG group, immunoreactivity of TGF-beta 1 was increased in glomeruli and tubuli. In the EG + L group, immunoreactivity of TGF-beta 1 was decreased compared to the EG group. Bax expression increased in the renal tubules of EG group and reduced in the EG + L group comparing to the control. In the EG + L group, the immunoreactivity of bcl-2 was increased in glomeruli. In EG + L treated group, number of caspase-3 immunopositive cells were decreased compared to all groups (P < 0.01). Apoptotic cells were increased in the EG-treated group compared to the other groups. Decreased apoptotic cell number was observed in the EG + L compared to the EG group (P < 0.01). Our findings suggest that losartan may provide a beneficial effect against tubulointerstitial damage and decrease renal tubular apoptosis caused by hyperoxaluria. © Springer-Verlag 2010

Effects of erucic acid supplemented feeding on chronic doxorubucin toxicity in rats

One of the undesired complications of the chemotherapy with doxorubicin is cardiotoxicity. Cardiac effect of erucic acid, which is a member of omega-9 fatty acid, is investigated on doxorubicin treatment in this study. Forty-eight rats were divided into eight groups and each group contained six rats. First group rats were fed with milk. In the third and fifth groups we fed rats with milk supplemented 0.5% and 5% erucic acid respectively. The groups 2, 4, 6 were fed as the groups 1, 3, 5 respectively; we injected 2 mg/kg twice weekly intraperitoneal doxorubicin to these groups whereas we injected isovolumous normal saline to the groups 1, 3, 5. Two other groups (groups 7 and 8) were fed with standard pellet. Group 8 received 2 mg/kg doxorubicin twice weekly; group 7 received normal saline. After 4 weeks hearts were isolated and mounted on a Langendorff apparatus perfused by modified Tyrode solution. Surviving rats were significantly less in erucic acid + doxorubicin groups at the end of the treatment period (p<0.05). No significant difference was found between groups for malondialdehyde, catalase, cytochrome c oxidase and isolated heart measurements. Concomitant application of erucic acid and doxorubicin showed profound toxicity