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Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats.
Biomed Pharmacother. 2017 Sep; 93:646-653.BP

Abstract

BACKGROUND

Cisplatin-induced nephrotoxicity is related to increased reactive oxygen species and inflammatory cytokines in the kidney. Sinapic acid (SA) has both antioxidant and anti-inflammatory activities.

AIMS

We determined the effects of SA on cisplatin-induced nephrotoxicity in rats, and the potential mechanisms by which it augments antioxidant responses and attenuates nephrotoxicity related to oxidative/nitrosative stress, apoptosis, and inflammation.

METHODS

Kidney function markers (i.e., serum urea, uric acid, creatinine, and lactate dehydrogenase), oxidative stress markers (i.e., lipid peroxidation and nitric oxide), antioxidant systems (i.e., superoxide dismutase, catalase, and reduced glutathione), inflammation markers (i.e., tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and myeloperoxidase [MPO]), apoptotic markers (caspase 3, Bax, and Bcl-2), and the levels of nuclear factor-κB (NF-κB [p65]), Nrf2, and heme oxygenase-1 (HO-1) were assessed. Histopathological examinations of the kidney were also used to evaluate cisplatin-induced nephrotoxicity.

KEY FINDINGS

SA (10 and 20mg/kg) pretreatment ameliorated kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels in cisplatin-injected rats, resulting in significant reductions in oxidative stress and replenishment of endogenous antioxidant enzymes. Cisplatin upregulated cytokines (i.e., TNF-α and IL-6) and MPO, increased apoptosis, and downregulated Nrf2 and HO-1. SA pretreatment downregulated the pro-apoptotic caspase-3 and Bax proteins, and upregulated the anti-apoptotic Bcl-2 protein. SA pretreatment also alleviated the extent of histological impairment and reduced neutrophil infiltration in renal tubules.

SIGNIFICANCE

The results suggest that the Nrf2/HO-1 signaling pathway may be the primary target for protection from cisplatin-induced nephrotoxicity by SA, and that SA reduces oxidative stress, inflammation, and apoptosis by inhibiting NF-κB.

Authors+Show Affiliations

Department of Pharmacology & Toxicology College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: muansari@ksu.edu.sa.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28686978

Citation

Ansari, Mushtaq Ahmad. "Sinapic Acid Modulates Nrf2/HO-1 Signaling Pathway in Cisplatin-induced Nephrotoxicity in Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 93, 2017, pp. 646-653.
Ansari MA. Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Biomed Pharmacother. 2017;93:646-653.
Ansari, M. A. (2017). Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 93, 646-653. https://doi.org/10.1016/j.biopha.2017.06.085
Ansari MA. Sinapic Acid Modulates Nrf2/HO-1 Signaling Pathway in Cisplatin-induced Nephrotoxicity in Rats. Biomed Pharmacother. 2017;93:646-653. PubMed PMID: 28686978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. A1 - Ansari,Mushtaq Ahmad, Y1 - 2017/07/04/ PY - 2017/04/04/received PY - 2017/06/12/revised PY - 2017/06/23/accepted PY - 2017/7/8/pubmed PY - 2018/4/26/medline PY - 2017/7/8/entrez KW - Apoptosis KW - Cisplatin-induced nephrotoxicity KW - Inflammation KW - Oxidative stress KW - Sinapic acid SP - 646 EP - 653 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 93 N2 - BACKGROUND: Cisplatin-induced nephrotoxicity is related to increased reactive oxygen species and inflammatory cytokines in the kidney. Sinapic acid (SA) has both antioxidant and anti-inflammatory activities. AIMS: We determined the effects of SA on cisplatin-induced nephrotoxicity in rats, and the potential mechanisms by which it augments antioxidant responses and attenuates nephrotoxicity related to oxidative/nitrosative stress, apoptosis, and inflammation. METHODS: Kidney function markers (i.e., serum urea, uric acid, creatinine, and lactate dehydrogenase), oxidative stress markers (i.e., lipid peroxidation and nitric oxide), antioxidant systems (i.e., superoxide dismutase, catalase, and reduced glutathione), inflammation markers (i.e., tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and myeloperoxidase [MPO]), apoptotic markers (caspase 3, Bax, and Bcl-2), and the levels of nuclear factor-κB (NF-κB [p65]), Nrf2, and heme oxygenase-1 (HO-1) were assessed. Histopathological examinations of the kidney were also used to evaluate cisplatin-induced nephrotoxicity. KEY FINDINGS: SA (10 and 20mg/kg) pretreatment ameliorated kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels in cisplatin-injected rats, resulting in significant reductions in oxidative stress and replenishment of endogenous antioxidant enzymes. Cisplatin upregulated cytokines (i.e., TNF-α and IL-6) and MPO, increased apoptosis, and downregulated Nrf2 and HO-1. SA pretreatment downregulated the pro-apoptotic caspase-3 and Bax proteins, and upregulated the anti-apoptotic Bcl-2 protein. SA pretreatment also alleviated the extent of histological impairment and reduced neutrophil infiltration in renal tubules. SIGNIFICANCE: The results suggest that the Nrf2/HO-1 signaling pathway may be the primary target for protection from cisplatin-induced nephrotoxicity by SA, and that SA reduces oxidative stress, inflammation, and apoptosis by inhibiting NF-κB. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28686978/Sinapic_acid_modulates_Nrf2/HO_1_signaling_pathway_in_cisplatin_induced_nephrotoxicity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)31619-0 DB - PRIME DP - Unbound Medicine ER -