Effect of some antihypertensive drugs on serum creatinine and tubulointerstitial index in adenine induced nephropathy in rats

ABSTRACT

The progression of chronic kidney disease [CKD] is more than just a simple, creeping loss of kidney function finally resulting in end-stage renal disease [ESRD]. The present study was intended to study the potential renoprotective effect of ramipril [angiotensin-converting enzyme inhibitors -ACEI] and valsartan [angiotensin receptor-1 blocker- ATI blacker] on adenine-induced nephropathy in rats. Also, to study the possible effect of combination of above mentioned drugs. Seventy- six male albino rats were used through out the study in Clinical Pharmacology Department, Mansoara University. Twelve rats were taken as negative control without any manipulation. Sixty four male albino rats were given adenine diet [I50mg] in 0.5 ml saline by gavage feeding once daily for 10 days to confirm induction of adenine-induced nephrotoxicity. Sixteen rats died during induction. Rats that survived, started treatment and divided into two main groups animals in each group were classified into 4 subgroups [each contain 6 rats], each of them took the test drugs once daily by stomach tube for 4 weeks Group I started treatment after 2 weeks from administration of adenine and Group II started treatment after 4 weeks from administration of adenine. The sera were taken for measurement of creatinine. The kidneys are rapidly dissected and put in formalin containing bottles and taken for pathological examination by H and E and special stains that included PAS and trichrome stains. Administration of each of -amipril, ualsartan and combination of both ramipril and valsartan showed that they produced highly significant reduction of the mean serum creatinine level [p<0.01, p<0.001, p<0.001] respectively as compared with the positive control. There was non-significant decrease of tubulointerstitial index when comparing ramipril treated group, valsartan treated group, and ramipril plus vaisartafi treated group, versus positive control group. We concluded that adenine induced nephropathy is important model in elucidating tubulointerstitial injury and coincident with chronic renal insufficiency. Drugs under the study play some degree of renoprotectin