Sinapic acid attenuates cisplatin-induced nephrotoxicity through peroxisome proliferator-activated receptor gamma agonism in rats

Abstract

A BSTRACT Aim: The aim of this study was to investigate the involvement of peroxisome proliferator-activated receptor gamma (PPAR-γ) in renal protection offered by sinapic acid in cisplatin-induced nephrotoxicity in male rats. Materials and Methods: Nephrotoxicity was induced by single dose of cisplatin (5 mg/kg, intraperitoneal [i.p.]) in rats. Cisplatin-induced nephrotoxicity was assessed by measuring serum creatinine, creatinine clearance, urea, uric acid, potassium, magnesium levels, fractional excretion of sodium, and microproteinuria in rats. Superoxide anion generation, thiobarbituric acid reactive substances, myeloperoxidase activity, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin and eosin stain showed renal histological changes. Results: The significant changes in serum and urinary parameters, elevated oxidative stress, and renal histological changes established the induction of nephrotoxicity. Sinapic acid treatment (20 and 40 mg/kg, orally [p.o.]) provides dose-dependent and significant ( P < 0.05) nephroprotection against cisplatin-mediated nephrotoxicity in rats. Nephroprotective effect of sinapic acid was abolished by PPAR-γ inhibitor, bisphenol A diglycidyl ether (30 mg/kg, i.p.) in rats. Conclusion: It is concluded that PPAR-γ agonism serves as one of the mechanisms in sinapic acid-mediated renoprotection.

Evaluation of the renoprotective effect of syringic acid against nephrotoxicity induced by cisplatin in rats

“…The microprotein, sodium, and creatinine clearance were also determined from urine samples by placing the rats in metabolic cages individually. After animal scarification, a portion of kidney tissue was preserved after fixing with formalin for histopathological studies and a small part of kidney tissue was used for assessment of superoxide anion generation (SAG) (Singh et al, 2020).…”

“…The remaining of kidney tissue was used for the estimation of myeloperoxidase (MPO) activity, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) as per the procedure described by Kapil et al (2013), Sehajpal et al (2014, Singh et al (2020). ELISA method was used for the estimation of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor kappa B (NF-κB) levels (Singh et al, 2020) and eNOS in renal tissue as per the procedure described by Czambel et al (2010) along with the instruction of the company manual.…”

“…The accumulation of CP is found to be five times more in kidney as compared to blood (Peres and da Cunha, 2013). Several studies indicates that CP accumulation in kidneys results in production of reactive oxygen species (ROS), inflammation, increases lipid peroxidation, and reduces the level of antioxidant, mitochondrial dysfunction along with deoxyribonucleic acid (DNA) adduct formation and free radicals mediated apoptotic pathways activation (Jilanchi et al, 2018;Manohar and Leung, 2018;Sultana et al, 2012).…”

“…Out of the natural compounds, phenolic acids which possess antioxidant and antiproliferative properties are considered as one of the potential groups of interest for pharmacological properties. Phenolic compounds are found in nuts, fruits, seeds, vegetables, and in all types of red wine and tea (Srinivasulu et al, 2018). Syringic acid (SA) is a natural active phenolic phytoconstituent 4-hydroxy-3, 5 dimethoxy benzoic acid isolated from honey, Radix isatidis, olive, grape, pomegranate, green tea, Isatis indigotica, and mushroom (Sancaktutar et al, 2014).…”

“…Previous studies established that that nitric oxide synthase (NOS)-mediated double-edge sword nitric oxide (NO) plays an imperative role in the pathobiology of nephrotoxicity induced via CP treatment by modulating the oxidative stress in renal tissues (Gharibi et al, 2017;Singh et al, 2019).…”