ABSTRACT
Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.
Subject(s)
Animals , Rats , Body Weight , Creatinine , Diabetes Mellitus , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Glucose , Kidney , Lipoproteins, HDL , Lisinopril , Streptozocin , Triglycerides , Urea , Vascular ResistanceABSTRACT
Effect of losartan was assessed on systemic haemodynamic responses to angiotensin II [Ang II] and adrenergic agonists in the model of high-fructose-fed rat. Twenty-four Sprague-Dawley [SD] rats were fed for 8 weeks either 20% fructose solution [FFR] or tap water [C] ad libitum. FFR or C group received losartan [10mg/kg/day p.o.] for 1 week at the end of feeding period [FFR-L and L] respectively, then the vasopressor responses to Ang II, noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. The responses [%] to NA, PE, ME and Ang II in FFR were lower [p<0.05] than C [FFR vs. C; 22 +/- 2 vs. 32 +/- 2, 30 +/- 3 vs. 40 +/- 3, 9 +/- 1 vs. 13 +/- 1, 10 +/- 1 vs. 17 +/- 1] respectively. L group had blunted [p<0.05] responses to NA, PE, ME and Ang II compared to C [L vs. C; 26 +/- 2 vs. 32 +/- 2, 30 +/- 3 vs. 40 +/- 3, 7 +/- 0.7 vs. 13 +/- 1, 5 +/- 0.4 vs. 17 +/- 1] respectively. FFR-L group had aggravated [p<0.05] response to NA and ME, but blunted response to Ang II compared to FFR [FFR-L vs. FFR; 39 +/- 3 vs. 22 +/- 2, 11 +/- 1 vs. 9 +/- 1, 3 +/- 0.4 vs. 10 +/- 1] respectively. Fructose intake for 8 weeks results in smaller vasopressor response to adrenergic agonists and Ang II. Data also demonstrated an important role played by Ang II in the control of systemic haemodynamics in FFR and point to its interaction with adrenergic neurotransmission