saroglitazar and Fibrosis

Obstructive nephropathy is a common clinical case that causes chronic kidney disease and ultimately progresses to end-stage renal disease. The activation of peroxisome proliferator-activated receptor-α (PPAR-α) reduces tubulointerstitial fibrosis and inflammation associated with obstructive nephropathy.. This study was carried out to investigate the potential effect of saroglitazar, dual PPAR-α/γ agonist, in alleviating renal fibrosis induced by unilateralureteral obstruction (UUO).. Twenty-four male Sprague Dawley rats were haphazardly divided into four groups of six rats each, including sham operated group, vehicle- or saroglitazar-treated UUO and saroglitazar groups. Rats received oral gavage of saroglitazar (3 mg/kg/day) for 13 days. On day 14, all rats were sacrificed; blood and renal tissues were collected.. Saroglitazar inhibited UUO-induced oxidative stress; it decreased the elevated levels of MDA and nitric oxide and increased levels of GSH and SOD in renal tissue. Moreover, saroglitazar repressed UUO-induced inflammation; it decreased the renal levels of nuclear factor kappa B (NF-κB) and interleukin-6 (IL-6). Furthermore, saroglitazar inhibited the accumulation of extracellular matrix via decreasing collagen, hydroxylproline and matrix metalloproteinase-9 (MMP-9) levels. Saroglitazar also decreased the expression of both the alpha smooth muscle actin (α-SMA) and tumor growth factor-beta (TGF-β). These effects were in parallel with reduction in mothers against decapentaplegic homolog 3 (smad3) expression and plasminogen activator inhibitor-1 (PAI-1) levels.. Collectively, the protective impact of saroglitazar might be attributed to its antioxidant, anti-inflammatory and anti-fibrotic effects against UUO-induced tubulointerstitial fibrosis through its regulatory effect on TGF-β1/Smad3 signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Fibrosis; Inflammation; Kidney Diseases; Male; Oxidative Stress; Phenylpropionates; PPAR alpha; PPAR gamma; Pyrroles; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta1; Ureteral Obstruction