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Front. Pharmacol. | doi: 10.3389/fphar.2019.01259

Corrigendum: Interference With Coagulation Cascade as a Novel Approach to Counteract Cisplatin-Induced Acute Tubular Necrosis; an Experimental Study in Rats

  • 1Nahda University, Egypt
  • 2Department of Pharmacology and Toxicology, Faculty of pharmacy, Beni-Suef University, Egypt
  • 3Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Egypt
  • 4Departnent of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Egypt
  • 5Department of Biochemistry, Faculty of Pharmacy, Minia University, Egypt
  • 6Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt

Coagulation system activation plays an important role in the pathophysiology of different
diseases. In spite of massive research regarding cisplatin-induced nephrotoxicity, the
role of coagulation cascade in such toxicity is still questionable. Here, we aim to
investigate the role of activation of coagulation system in the initiation of cisplatininduced acute renal tubular necrosis. Moreover, the role of the anticoagulant rivaroxaban
against such toxicity was investigated. Briefly, animals were classified into seven groups,
eight rats each. Group 1 served as normal control group, groups (2–7) received i.p.
single doses of cisplatin (6 mg/kg b.w), groups (6–7) were treated with rivaroxaban (5
and 7 mg/kg b.w, p.o., respectively) 7 days before cisplatin injection and completed for
4 days. Animals in groups (2, 3, and 4) were sacrificed after 1, 2 and 3 days of cisplatin
injection, respectively, while groups (1, 5, 6, and 7) were sacrificed after 4 days of
cisplatin injection. Serum cystatin-c, urea, creatinine and g-glutamyl transferase, urinary
Lipocaline-2, and KIM-1 protein densities, as well as glomerular filtration rate (GFR)
were assessed. Immunofluorescence examination of glomeruli fibrin and tissue factor
(TF) was also performed coupled with a histopathological study. Cisplatin administration
increased expression of fibrin and TF starting 24 h of cisplatin injection even before renal
failure markers elevated. Leukocytosis, thrombocytopenia, and increased prothrombin
time were also observed. Cisplatin also induced tubular damage evidenced by increased
serum cystatin-c, urea, and creatinine with significant decrease in GFR and Gamma
glutamyl transferase (GGT) activity. Rivaroxaban significantly decreased elevation of
fibrin and TF with significant reduction in serum creatinine, BUN and cystatin-c levels.
Rivaroxaban also significantly improved hematological markers and histological features
as well. This study showed that activation of coagulation system plays an important role
in the pathophysiology of cisplatin-induced acute renal tubular damage. Interference
with coagulation cascade may be a promising nephroprotective strategy against
chemical nephrotoxicity

Keywords: Coagulation Cascade, Cisplatin, rivaroxaban, Fibrin, tissue factor, nephrotoxicity

Received: 06 Sep 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Ewees, Messiha, Abo-Saif, Bayoumi and Abdel-Bakky. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mohamed G. Ewees, Nahda University, Beni Suef, Egypt, mohamed_pharma86@yahoo.com