Nephroprotective effect of Vanillic acid in STZ-induced diabetic rats

Abstract

Purpose: To investigate the protective effect of vanillic acid (VA) in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats.

Methods: Experimental diabetes mellitus in rats was induced by intraperitoneally administration of single dose of STZ (55 mg/kg). The animals were divided into 5 groups viz., normal control, diabetic control, glimepiride (0.5 mg/kg, orally) and VA treatment (50 and 100 mg/kg, orally) groups. The treatment was started after the confirmation of hyperglycemia (> 250 mg/dl) and continued for 6 weeks. Serum glucose level, and body weight were measured weekly. At the end of study, HbA1c in whole blood, insulin, lipid profile, urea, creatinine and albumin in serum. Creatinine and albumin were measured in urine along with creatinine clearance. In addition, kidney weight and histopathology were assessed.

Results: Treatment with VA markedly attenuated STZ-induced body weight loss and hyperglycemia, along with improved lipid profile and HbA1c, without significant alteration of serum insulin levels. It also decreased urea, creatinine and increased albumin in serum. Moreover, VA, significantly reduced urine volume, urinary albumin along with marked improvement in creatinine clearance. Further, the VA treatment significantly reverse the raised levels of oxidative stress markers, pro-inflammatory and fibrotic markers viz. TNF-α, IL-1β, IL-6, TGF-β1 and NFκB activity in kidney tissue. These effects are associated with amelioration of histopathological alterations compared to diabetic control rats. While glimepiride produced similar antihyperglycemic effect but the effect on albuminuria, oxidative stress markers and cytokine levels were less significant as compared to VA (100 mg/kg).

Conclusions: In conclusion, VA exhibited nephroprotective effect through amelioration of kidney dysfunction and damage in diabetic rats. The observed nephroprotective effect of VA may be ascribed to inhibition of hyperglycemia induced oxido-inflammatory stress and necroptosis of renal tissue possibly due to its antihyperglycemic, antioxidant and anti-inflammatory actions.

Keywords: Albuminuria; Antioxidants; Gimepiride; Insulin; Necroptosis; Vanillic acid.

Fig. 1

Effect of VA on histopathological changes in H & E stained renal tissue (X400). a Normal control: showing normal architecture of glomerular capillaries (green arrows), mesangial cells (orange arrow), Bowman’s capsule (blue arrow). b STZ, Diabetic control: showing glomerulosclerosis (yellow arrows) and increased glomerular space (blue arrow). c STZ+ Glimepiride (0.5mg/kg): showing increased mesangial matrix (red arrows). d STZ+VA (50 mg/kg): showing degeneration of capillary network (orange arrows). e STZ+VA (100mg/kg): showing glomerular capillaries normal (green arrows) and slight mesangial expansion (orange arrow)

Fig. 2

Effect of VA on histopathological changes in PAS stained renal tissue (X400). a Normal control: showing normal glomerular capillaries (green arrows), glomerular basement membrane (blue arrow) and mesangial region (orange arrow). b STZ, Diabetic control: showing glomerulosclerosis (yellow arrow), thick glomerular basement membrane (blue arrow) and increased mesangial matrix (orange arrow). c STZ+ Glimepiride (0.5mg/kg): showing focal glomerulosclerosis (orange arrows). d STZ+ VA (50 mg/kg) : showing focal glomerulosclerosis (orange arrows). e STZ+ VA (100mg/kg) : showing normal architecture of glomerular capillaries (green arrows), glomerular basement membrane (blue arrow) and slight mesangial expansion (orange arrow)

Fig. 3

Effect of VA on histopathological changes in MTS stained renal tissue (X400) a Normal control: showing normal histology of glomerulus (green arrows). b STZ, Diabetic control: showing collagen deposition in glomerulus and tubules (yellow arrows). c STZ+ Glimepiride (0.5mg/kg): showing lesser collagen deposition (red arrow). d STZ+ VA (50 mg/kg) : showing increasedcollagen deposition (red arrows). e STZ+ VA (100mg/kg) : showing normal architecture of glomerulus (green arrows) and insignificant collagen deposition (orange arrow) when compared with the diabetic control group