Effect Of Iodinated Contrast Media On Renal Damage In The Aging Male Rat

Purpose To study the effect of iodinated contrast media on renal damage in the aging male rat and assess whether elder age is a risk factor for the development of contrast-induce nephropathy(CIN);to explore the effects of angiotensin-converting enzyme(ACE), transcription factor Sp 1 and oxidative stress on nephrotoxicity caused by exposure to iodinated contrast media in the aging male rat.Methods According to the age category,48 healthy Sprague-Dawley male rats were firstly divided into three age groups(n=12/group):young(4months),middle-age(12 months) and elder(24 months) group.And then each age group was randomly divided into NS control group and contrast media group.That is,there were six sub-groups,named the young NS control group(YNS),the young contrast meida group(YCM),the middle-age NS control group(MNS),the middle-age contrast meida group(MCM),the elder NS control group(ENS),the elder contrast meida group(ECM).After being diprived of water for 24 h,all three contrast media groups were injected intravascular with 10 ml/kg b.w.of 76%diatrizoate through a caudal vein.At the same time,the other three NS control group were injected with equal volumes of saline.Urine of 24 h before and after administration were collected to detect urine creatinine(UCr) and enzyme activivty of urine N-acety1-beta-D-glucosaminidase(U_NAG).Urine of 24-48 h after administration were continually collectd to detct UCr.48 h later,blood samples were obtained to detect the level of serum creatinine(SCr) and calculate endogenous creatinine clearance rate(Ccr). The left kidney was homogenated to detect malondialdehyde(MDA) level and ACE activity.The fight kidney tissue was fixed by 10%buffered formalin and embedded in paraffin.The kidney samples were cut to sections of two micron and stained by hematoxylin and eosin staining. Histological changes were observed and scored semiquantitatively.The expression of Sp1 protein in renal tissue was measured by immunity histochemistry.Results Compared with ENS group,ECM group showed an evident increase in SCr by＞25%from baseline(P＜0.01) and a decline in Ccr(P＜0.05) after contrast media administration.In ECM group,the enzyme activity of U_NAG 24 h after contrast media administration was significantly higher than 24 h before that(P＜0.001).The levels of ACE and MDA were also increased in renal tissues(P＜0.001,P＜0.01).Scores of tubular injury and index of kidney weight/body weight rose significantly(P＜0.001,P＜0.05).The expression of Sp1 protein in renal tissue was significantly upgratulated(P＜0.01).Compared with MNS group,the level of SCr in MCM group was increased by＜25%from baseline(P＜0.05).There was an increasing trend but no significant statistic difference in levels of MDA and ACE in renal tissue,scores of tubular injury,index of kidney weight/body weight,and expression of Sp1 protein between MNS group and MCM group.Compared with YNS group,YCM group showed no significant difference in all above parameters.Conclusions Angiotensin-converting enzyme(ACE),transcription factor Sp1 and oxidative stress played a role in nephrotoxcity induced by iodinated contrast media in the aging male rat.Elder age is a risk factor for the development of contrast media-induce nephropathy(CIN) in rat.