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Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats.
Chem Biol Interact. 2020 Jan 05; 315:108863.CB

Abstract

Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and the potential mechanisms in rats. Rats were randomly divided into four groups as follows: group1: normal control, group 2: received gentamicin only (100 mg/kg intraperitoneally), group 3: concurrently received gentamicin and celecoxib (30 mg/kg, orally) and group 4: received celecoxib. Celecoxib administration decreased gentamicin-induced rise in kidney weight, renal somatic index (RSI), blood urea nitrogen (BUN), serum creatinine (Cr), protein in urine, lactate dehydrogenase (LDH), nitric oxide (NOx), meanwhile, it increased serum albumin, urine Cr level and creatinine clearance (CCr), increased the renal endogenous antioxidant status, revealed by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH). Gentamicin-induced elevated nuclear factor kappa B-P65 subunit (NFκB-p65), tumor necrosis factor-alpha (TNF-α) and apoptotic markers (tumor suppressor protein (p53) and caspase-3) protein levels were significantly decreased upon celecoxib treatment. Moreover, celecoxib suppressed renal myeloperoxidase (MPO) activity and posed improvement of histological features. In immunohistochemistry, celecoxib-treated rats showed decreased immunoreactivity against COX-2 in tubular cells and a mild positive immunoreactivity against heat shock protein 70 (HSP70) in renal interstitial cells. These findings propose that celecoxib treatment mitigates renal dysfunction via decreasing renal inflammation, oxidative/nitrosative stress, and apoptosis.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taibah University, Al-Madina Al-Munawwarah, 30001, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt. Electronic address: marwaelsayed90@mans.edu.eg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31628940

Citation

Abdelrahman, Rehab S., and Marwa E. Abdelmageed. "Renoprotective Effect of Celecoxib Against Gentamicin-induced Nephrotoxicity Through Suppressing NFκB and Caspase-3 Signaling Pathways in Rats." Chemico-biological Interactions, vol. 315, 2020, p. 108863.
Abdelrahman RS, Abdelmageed ME. Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats. Chem Biol Interact. 2020;315:108863.
Abdelrahman, R. S., & Abdelmageed, M. E. (2020). Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats. Chemico-biological Interactions, 315, 108863. https://doi.org/10.1016/j.cbi.2019.108863
Abdelrahman RS, Abdelmageed ME. Renoprotective Effect of Celecoxib Against Gentamicin-induced Nephrotoxicity Through Suppressing NFκB and Caspase-3 Signaling Pathways in Rats. Chem Biol Interact. 2020 Jan 5;315:108863. PubMed PMID: 31628940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renoprotective effect of celecoxib against gentamicin-induced nephrotoxicity through suppressing NFκB and caspase-3 signaling pathways in rats. AU - Abdelrahman,Rehab S, AU - Abdelmageed,Marwa E, Y1 - 2019/10/16/ PY - 2019/07/26/received PY - 2019/09/28/revised PY - 2019/10/12/accepted PY - 2019/10/20/pubmed PY - 2020/2/23/medline PY - 2019/10/20/entrez KW - Caspase-3 KW - Celecoxib KW - Gentamicin KW - NFκB KW - Nephrotoxicity KW - p53 SP - 108863 EP - 108863 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 315 N2 - Gentamicin-induced nephrotoxicity has been well documented, although the causing mechanisms and preventative measures need further investigation. The current study aimed to explore the potential protective impacts of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on gentamicin-induced nephrotoxicity and the potential mechanisms in rats. Rats were randomly divided into four groups as follows: group1: normal control, group 2: received gentamicin only (100 mg/kg intraperitoneally), group 3: concurrently received gentamicin and celecoxib (30 mg/kg, orally) and group 4: received celecoxib. Celecoxib administration decreased gentamicin-induced rise in kidney weight, renal somatic index (RSI), blood urea nitrogen (BUN), serum creatinine (Cr), protein in urine, lactate dehydrogenase (LDH), nitric oxide (NOx), meanwhile, it increased serum albumin, urine Cr level and creatinine clearance (CCr), increased the renal endogenous antioxidant status, revealed by decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and reduced glutathione (GSH). Gentamicin-induced elevated nuclear factor kappa B-P65 subunit (NFκB-p65), tumor necrosis factor-alpha (TNF-α) and apoptotic markers (tumor suppressor protein (p53) and caspase-3) protein levels were significantly decreased upon celecoxib treatment. Moreover, celecoxib suppressed renal myeloperoxidase (MPO) activity and posed improvement of histological features. In immunohistochemistry, celecoxib-treated rats showed decreased immunoreactivity against COX-2 in tubular cells and a mild positive immunoreactivity against heat shock protein 70 (HSP70) in renal interstitial cells. These findings propose that celecoxib treatment mitigates renal dysfunction via decreasing renal inflammation, oxidative/nitrosative stress, and apoptosis. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/31628940/Renoprotective_effect_of_celecoxib_against_gentamicin_induced_nephrotoxicity_through_suppressing_NFκB_and_caspase_3_signaling_pathways_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(19)31275-X DB - PRIME DP - Unbound Medicine ER -