P-Coumaric acid alleviates experimental diabetic nephropathy through modulation of Toll like receptor-4 in rats

Diabetic nephropathy (DN) is responsible for the occurrence of 30-47% of the incident cases of end-stage renal disease (ESRD) worldwide. DN is a chronic inflammatory disorder, which results from hyperglycemia-induced alterations and leads to renal fibrosis and ESRD. Toll like receptor-4 (TLR-4) participates in regulation of inflammatory response through controlling of innate immune system. P-Coumaric Acid (P-CA) is a natural hydroxycinnamic acid derivative and is widely present in vegetables, fruits, mushrooms and cereals. This study aimed to explore the renoprotective effect of P-CA, as anti-inflammatory and antioxidant natural compound, against experimental DN.

DN was induced by single intraperitoneal injection of streptozotocin (45 mg/kg) in rats. In kidney homogenate, levels of TLR-4, interleukin-6 (IL-6) and transforming growth factor β1 (TGFβ1) were measured using ELISA technique. Also, kidney collagen content was determined colorimetrically.

Oral administration of P-CA (100 mg/kg) for 8 weeks significantly alleviated the DN. P-CA significantly reduced serum concentrations of glucose, creatinine, blood urea nitrogen (BUN) and reduced protein content in urine. Also, P-CA significantly increased superoxide dismutase (SOD) activity and significantly reduced kidney contents of malondialdehyde (MDA), TLR-4, IL-6, TGFβ1 and collagen when compared with DN group. Moreover, P-CA significantly improved DN-induced histopathological abnormalities.

P-CA confers protection against the progression of DN. This renoprotective effect can be attributed to its ability to decrease the generation of inflammatory and fibrotic cytokines in addition to restoring oxidant/antioxidant balance through its ability to down-regulate TLR-4 activation.