title: Renoprotective effects of angiotensin receptor blocker and stem cells in acute kidney injury: Involvement of inflammatory and apoptotic markers.
abstract: Cisplatin, Cis-diamminedichloroplatinum (CDDP), is a platinum-based chemotherapy drug, and its chemotherapeutic use is restricted by nephrotoxicity. Inflammatory and apoptotic mechanisms play a central role in the pathogenesis of CDDP-induced acute kidney injury (AKI). The aim of this study was to compare the therapeutic potential of candesartan, angiotensin II receptor blocker, versus bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of CDDP-induced nephrotoxicity. Adult male Wistar rats (n = 40) were divided into four groups; Normal control: received saline injection, CDPP group: received CDDP injection (6 mg/kg single dose), Candesartan group: received candesartan (10 mg/kg/day) for 10 days + CDDP at day 3, and Stem cells group: received CDDP + BM-MSCs intravenously one day after CDDP injection. The rats were sacrificed seven days after CDDP injection. Significant elevation in serum creatinine and urea, renal levels of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1, renal expressions of nuclear factor kappa B (NF-κB), p38-mitogen-activated protein kinase (MAPK), caspase-3 and Bcl-2-associated x protein (Bax) were found in CDDP-injected rats when compared to normal rats. Both candesartan and BM-MSCs ameliorated renal function and reduced significantly the inflammatory markers (TNF-α , NF-κB, p38-MAPK and MCP-1) and apoptotic markers (caspase-3 and Bax) in renal tissue after CDDP injection. Candesartan as well as BM-MSCs have anti-inflammatory and anti-apoptotic actions and they can be used as nephroprotective agents against CDDP-induced nephrotoxicity. BM-MSCs is more effective than candesartan in amelioration of AKI induced by CDDP.
authors.affiliation: Pharmaceutical Sciences Department, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Kingdom of Saudi Arabia iosherif@pnu.edu.sa.
authors.forename: Iman O
authors.initials: IO
authors.lastname: Sherif
authors.affiliation: Chemistry Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Kingdom of Saudi Arabia.
authors.forename: Laila A
authors.initials: LA
authors.lastname: Al-Mutabagani
authors.affiliation: Pharmaceutical Sciences Department, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 11671, Kingdom of Saudi Arabia.
authors.forename: Anwar M
authors.initials: AM
authors.lastname: Alnakhli
authors.affiliation: Zoology Department, College of Science, Urology and Nephrology Center, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Sobh
authors.affiliation: Biochemistry Department, College of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
authors.forename: Hoda E
authors.initials: HE
authors.lastname: Mohammed
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000032:analysis; D018932:Chemokine CCL2 / Q000032:analysis; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D005434:Flow Cytometry; D007249:Inflammation / Q000503:physiopathology*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D016328:NF-kappa B / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013777:Tetrazoles / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016328:NF-kappa B; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D002945:Cisplatin; C081643:candesartan
keywords: Angiotensin receptor blocker; apoptosis; inflammation; renal injury; stem cells
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