Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats.
OBJECTIVE
In this study, the renoprotective functions of sinapic acid (SA), a polyphenol, on gentamicin-induced nephrotoxicity and the pathway that mediates this function were examined.


METHODS
Kidney function markers (serum urea, uric acid, creatinine, LDH, and γ-GGT) and histopathological examinations of the kidney were used to evaluate gentamicin-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.


RESULTS
SA (10 and 20mg/kg) pretreatment along with gentamicin restored kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels, resulting in significant decreases in oxidative and nitrosative stress. Gentamicin promoted the upregulation of renal cytokines (TNF-α and IL-6), nuclear NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity were significantly down regulated upon SA pretreatment. Furthermore, SA pretreatment downregulated caspase 3 and Bax protein expressions and upregulated Bcl-2 protein expression. SA pretreatment also mitigated the magnitude of histological damage and reduced neutrophil infiltration in renal tubules.


CONCLUSIONS
These outcomes indicated that SA pretreatment mitigates renal impairment and structural injuries via the downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney.
Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: muansari@ksu.edu.sa.
Mushtaq Ahmad
MA
Ansari
Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Mohammad
M
Raish
Clinical Pharmacy, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Ajaz
A
Ahmad
Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Sheikh Fayaz
SF
Ahmad
Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
Shahid
S
Mudassar
Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Kazi
K
Mohsin
Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Faiyaz
F
Shakeel
Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Hesham M
HM
Korashy
Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Saleh A
SA
Bakheet
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003373:Coumaric Acids / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005839:Gentamicins / Q000009:adverse effects*; D007249:Inflammation / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D015538:Nitrosation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D003373:Coumaric Acids; D016207:Cytokines; D005839:Gentamicins; C073734:sinapinic acid
Apoptosis; Gentamicin-induced nephrotoxicity; Inflammation; Nitrosative stress; Oxidative stress; Sinapic acid