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.
ABSTRACT
Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins. Hematoxylin-eosin, periodic acid Schiff and Masson trichrome staining confirmed renal pathological changes in diabetic rats that included glomerular capsular wall distortion, mesangial cell expansion, glomerular microvascular condensation, tubular damage and degeneration and fibrosis. Low-dose fenofibrate (30mg/kg, p.o., 4 weeks) and low-dose dipyridamole (20mg/kg, p.o., 4 weeks) treatment either alone or in combination considerably reduced renal structural and functional abnormalities in diabetic rats, but without affecting the elevated glucose level. Fenofibrate, but not dipyridamole, significantly prevented the lipid alteration and importantly the uric acid elevation in diabetic rats. Lisinopril (5mg/kg, p.o., 4 weeks, reference compound), prevented the hyperglycemia, lipid alteration and development of diabetic nephropathy. Lipid alteration and uric acid elevation, besides hyperglycemia, could play key roles in the development of nephropathy. Low-doses of fenofibrate and dipyridamole treatment either alone or in combination markedly prevented the diabetes-induced nephropathy. Their combination was as effective as to their individual treatment, but not superior in preventing the development of diabetic nephropathy.
