Sinapic acid ameliorate cadmium-induced nephrotoxicity: In vivo possible involvement of oxidative stress, apoptosis, and inflammation via NF-κB downregulation
SA, Ansari MA, Raish M, Ahmad A, Alkharfy KM, Ahmad SF, Attia SM, Alsaad AM, Bakheet . 2017
Cadmium (CD), an environmental and industrial pollutant, generates reactive oxygen species (ROS) and NOS responsible for oxidative and nitrosative stress that can lead to nephrotoxic injury, including proximal tubule and glomerulus dysfunction. Sinapic acid (SA) has been found to possess potent antioxidant and anti-inflammatory effects in vitro and in vivo. We aimed to examine the nephroprotective, anti-oxidant, anti-inflammatory, and anti-apoptotic effects of SA against CD-induced nephrotoxicity and its underlying mechanism. Kidney functional markers (serum urea, uric acid, creatinine, LDH, and calcium) and histopathological examinations of the kidney were used to evaluate CD-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-κB [p65], TNF-α, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed. SA (10 and 20mg/kg) pretreatment restored kidney function, upregulated antioxidant levels, and prevented the elevation of lipid peroxidation and nitric oxide levels, significantly reducing oxidative and nitrosative stress. CD upregulated renal cytokine levels (TNF-α, IL-6), nuclear NF-κB (p65) expression, NF-κB-DNA-binding activity, and MPO activity, which were significantly downregulated upon SA pretreatment. Furthermore, SA treatment prevented the upregulation of caspase 3 and Bax protein expression and upregulated Bcl-2 protein expression. SA pretreatment also alleviated the magnitude of histological injuries and reduced neutrophil infiltration in renal tubules. We conclude that the nephroprotective potential of SA in CD-induced nephrotoxicity might be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential via downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney.
The tyrosine kinase inhibitor sunitinib was recently approved for use against gastrointestinal stromal tumors and advanced renal cell carcinoma. Yet, the protective effect of sunitinib against…
Psoriatic patients have systemic inflammation as well as oxidative stress, which are associated with cardiovascular disorders such as atherosclerosis, hypertension myocardial infarction, and…
Cadmium (CD), an environmental and industrial pollutant, generates reactive oxygen species (ROS) and NOS responsible for oxidative and nitrosative stress that can lead to nephrotoxic injury,…