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      L-Carnitine Mitigates Oxidative Stress and Disorganization of Cytoskeleton Intermediate Filaments in Cisplatin-Induced Hepato-Renal Toxicity in Rats

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          Abstract

          Cisplatin (CP) is one of the most active medications in cancer treatment and has some adverse effects such as hepatotoxicity and nephrotoxicity. The present research was planned to determine the protective effects of L-carnitine (LC) against CP-induced hepato-renal oxidative stress in rats, via investigating of some serum biochemical and tissue oxidative/antioxidant parameters, histological alterations, and immunohistochemical expressions of two different intermediate filaments (IFs) proteins; vimentin (VIM) and cytokeratin 18 (CK18). Twenty-eight rats were divided into four groups (7 rats each). Groups I and II were orally administered saline and LC (100 mg/kg body weight), respectively, once daily for 30 consecutive days. Group III received saline orally once daily and a single dose of CP on the 27th day of the experiment [7.5 mg/kg, intraperitoneal (IP)]. Group IV received both LC and CP. Injection of CP significantly ( P ≤ 0.05) increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities and creatinine and urea levels, while serum total protein, albumin, and globulin concentrations significantly ( P ≤ 0.05) decreased. In addition, CP induced a dramatic increase in the Malondialdehyde (MDA) level along with a substantial decrease in reduced glutathione (GSH) and catalase (CAT) in the hepato-renal tissues. Histologically, both liver and kidney of the CP treated group revealed marked degenerative changes. Moreover, overexpression of both VIM and CK18 in hepato-renal tissues were noted after CP injection. On the other hand, the administration of LC in the CP injected group (Group IV) restored the biochemical parameters, histological, and immunohistochemical pictures toward the normalcy. In conclusion, LC may be supplemented for chemotherapy with CP to ameliorate its oxidative stress and restore the normal organization of IFs, especially VIM and CK18 within the CP intoxicated hepato-renal cells.

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          Most cited references 73

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          Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.

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            Mechanisms of Cisplatin Nephrotoxicity

            Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention.
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              [13] Catalase in vitro

               Hugo Aebi (1984)
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                29 September 2020
                2020
                : 11
                Affiliations
                1 Department of Pharmacology, Faculty of Veterinary Medicine, Benha University , Toukh, Egypt
                2 Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Matrouh University , Matrouh, Egypt
                3 Department of Biochemistry, Faculty of Veterinary Medicine, Matrouh University , Matrouh, Egypt
                4 Department of Histology, Faculty of Veterinary Medicine, Benha University , Toukh, Egypt
                5 Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University , Toukh, Egypt
                6 Department of Zoology, College of Science, King Saud University , Riyadh, Saudi Arabia
                7 Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University , Ismailia, Egypt
                Author notes

                Edited by: Mosaad A Abdel-Wahhab, National Research Centre, Egypt

                Reviewed by: Yasser S. El-Sayed, Damanhour University, Egypt; Ahmed Esmat Abdel Moneim, Helwan University, Egypt; Saad Hussin Alkahtani, King Saud University, Saudi Arabia; Basiru Olaitan Ajiboye, Afe Babalola University, Nigeria

                *Correspondence: Sabreen Ezzat Fadl, nourmallak@ 123456yahoo.com

                This article was submitted to Predictive Toxicology, a section of the journal Frontiers in Pharmacology

                †ORCID: Mohamed Aboubakr, orcid.org/0000-0003-1719-4844; Ehab Yahya Abdelhiee, orcid.org/0000-0002-2276-877X; Sabreen Ezzat Fadl, orcid.org/0000-0001-5541-6159; Mohamed M. Abdel-Daim, orcid.org/0000-0002-4341-2713

                Article
                10.3389/fphar.2020.574441
                7552923
                Copyright © 2020 Elkomy, Abdelhiee, Fadl, Emam, Gad, Sallam, Alarifi, Abdel-Daim and Aboubakr

                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.

                Page count
                Figures: 6, Tables: 4, Equations: 0, References: 75, Pages: 12, Words: 5237
                Funding
                Funded by: King Saud University 10.13039/501100002383
                Award ID: RSP 2020/27
                Categories
                Pharmacology
                Original Research

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