Korean J Physiol Pharmacol.  2016 Jul;20(4):333-340. 10.4196/kjpp.2016.20.4.333.

Effect of edaravone in diabetes mellitus-induced nephropathy in rats

• Varatharajan R
• Lim LX
• Tan K
• Tay CS
• Teoh YL
• Akhtar SS
• Rupeshkumar M
• Chung I
• Abdullah N
• Banik U
• Dhanaraj S
• Balakumar

• KMID: 2371050
• DOI: http://doi.org/10.4196/kjpp.2016.20.4.333

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.

Keyword

Diabetic nephropathy; Edaravone; Lipid alteration; Renoprotection

MeSH Terms

Animals
Body Weight
Creatinine
Diabetes Mellitus
Diabetes Mellitus, Experimental
Diabetic Nephropathies
Glucose
Kidney
Lipoproteins, HDL
Lisinopril
Rats*
Streptozocin
Triglycerides
Urea
Vascular Resistance
Creatinine
Glucose
Lipoproteins, HDL
Lisinopril
Streptozocin
Triglycerides
Urea

Figure

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  Fig. 1 Effect of edaravone on body weight at week 10.Data are expressed as mean±SEM. Body weight did not statistically differ among the five study groups.

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  Fig. 2 Effect of edaravone on kidney weight to body weight ratio (KW/BW).Data are expressed as mean±SEM. aaap<0.001 vs Normal control; bp<0.05; bbbp<0.001 vs Diabetic control.

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  Fig. 3 Effect of edaravone on blood glucose (mg/dL) concentration.Data are expressed as mean±SEM. aap<0.01 vs Normal control; bp<0.05 vs Diabetic control.

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  Fig. 4 Effect of edaravone on serum creatinine (mg/dL) concentration.Data are expressed as mean±SEM aaap<0.001 vs Normal control; bp<0.05 vs Diabetic control.

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  Fig. 5 Effect of edaravone on serum urea (mg/dL) concentration.Data are expressed as mean±SEM. aaap<0.001 vs Normal control; bbp<0.01 vs Diabetic control.

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  Fig. 6 Effect of edaravone on serum triglycerides (mg/dL) concentration.Data are expressed as mean±SEM. aap<0.01 vs Normal control; bp<0.05 and bbp<0.01 vs Corresponding Diabetes control.

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  Fig. 7 Effect of edaravone on serum HDL (mg/dL) concentration.Data are expressed as mean±SEM. aap<0.01 vs Normal control; bp<0.05 and bbp<0.01 vs Corresponding Diabetes control.

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  Fig. 8 Effect of edaravone on renal histology using Haematoxylin and eosin staining.

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  Fig. 9 Effect of edaravone on renal histology using Periodic acid-Schiff staining.

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  Fig. 10 Effect of edaravone on renal histology using Masson trichrome staining.

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