Effects of fructose-1, 6-diphosphate on adriamycin induce myocardial tyrosine nitration in rats / 中国药理学通报

ABSTRACT

AIM: To study the effect of fructose-1, 6-diphosphate (FDP) on adriamycin (ADM) induced myocardial tyrosine nitration in rats. METHODS: Rats were treated with ADM by intraperitoneal injection (2.50 mg·kg-1 body weight at six times every other day), and then the ADM treated rats were intervened by FDP on different dosages by intraperitoneal injection (at twenty-one times every other day). TBA method, nitrate reductase method and pyrogallol autoxidation method were used to determine the content of lipid peroxide (LPO) and nitric oxide (NO), the activity of superoxide dismutase (SOD) of myocardium, respectively. The nitrotyrosine (NT) and expression of inducible nitric oxide synthase (iNOS) mRNA of myocardium was detected by immunohistochemical method and in situ hybridization. The expression level of iNOS mRNA and level of NT in myocardium was semi-quantitatively analyzed. RESULTS: FDP (300, 600, 1 200 mg·kg-1) significantly reduced the content of LPO and NO in myocardium, the expression level of iNOS mRNA and level of NT in myocardium, and significantly increased the activity of SOD in myocardium, when ADM treated rats were intervened by FDP (P<0.01). CONCLUSION: FDP can inhibit myocardial tyrosine nitration induced by ADM, and thereby reduce injury of cardiotoxicity induced by ADM. The mechanism may be relate to FDP inhibit expression of iNOS mRNA in myocardium induced by ADM, reduce to produce NO in myocardium, and it protect the activity of SOD in myocardium, enhance capability of scavenge superoxide anion in myocardiurn, thereby reducing to produce peroxynitrite in myocardium.