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      Synergistic protective effects of lycopene and N-acetylcysteine against cisplatin-induced hepatorenal toxicity in rats

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          Abstract

          Cisplatin (CP) is one of the most frequently used chemotherapy agents. The objective of this design was to determine the ameliorative effect of lycopene (LP) and/or N-acetylcysteine (NAC) in rats with hepatic and renal toxicity induced by CP. Rats were divided randomly into 7 groups (7 rats/group): control vehicle group (saline only), the LP group (10 mg/kg, orally), the NAC group (150 mg/kg, orally), the CP group (7.5 mg/kg, IP on day 27), the LP-CP group, the NAC-CP group, and the LP-NAC-CP group. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (APK), and levels of urea, creatinine, and lipids (cholesterol, triglycerides, and low-density lipoprotein-cholesterol) increased after CP injection in the serum. Moreover, CP decreased levels of protein, albumin, and HDL cholesterol. Meanwhile, malondialdehyde significantly increased with a decrease in reduced glutathione, superoxide dismutase, and catalase in the liver and kidney tissues. CP also induced some pathological lesions and increased the expression of caspase-3 in the liver and kidney tissues. Administration of LP and NAC alone or in combinations ameliorated hepatorenal toxicity and apoptosis induced by CP.

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          Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

          Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
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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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              The chemistry and biological activities of N-acetylcysteine.

              N-acetylcysteine (NAC) has been in clinical practice for several decades. It has been used as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/AIDS, heavy metal toxicity and psychiatric disorders. The mechanisms underlying the therapeutic and clinical applications of NAC are complex and still unclear. The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry. The antioxidative activity of NAC as of other thiols can be attributed to its fast reactions with OH, NO2, CO3(-) and thiyl radicals as well as to restitution of impaired targets in vital cellular components. NAC reacts relatively slowly with superoxide, hydrogen-peroxide and peroxynitrite, which cast some doubt on the importance of these reactions under physiological conditions. The uniqueness of NAC is most probably due to efficient reduction of disulfide bonds in proteins thus altering their structures and disrupting their ligand bonding, competition with larger reducing molecules in sterically less accessible spaces, and serving as a precursor of cysteine for GSH synthesis. The outlined reactions only partially explain the diverse biological effects of NAC, and further studies are required for determining its ability to cross the cell membrane and the blood-brain barrier as well as elucidating its reactions with components of cell signaling pathways. Copyright © 2013 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                mohamedaboubakrm@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                7 July 2021
                7 July 2021
                2021
                : 11
                : 13979
                Affiliations
                [1 ]GRID grid.411660.4, ISNI 0000 0004 0621 2741, Department of Pharmacology, Faculty of Veterinary Medicine, , Benha University, ; 13736 Moshtohor, Toukh, Qaliobiya Egypt
                [2 ]GRID grid.411660.4, ISNI 0000 0004 0621 2741, Department of Histology, Faculty of Veterinary Medicine, , Benha University, ; 13736 Moshtohor, Toukh, Qaliobiya Egypt
                [3 ]GRID grid.411660.4, ISNI 0000 0004 0621 2741, Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, , Benha University, ; 13736 Moshtohor, Toukh, Qaliobiya Egypt
                [4 ]Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Matrouh University, Matrouh, Egypt
                [5 ]GRID grid.411978.2, ISNI 0000 0004 0578 3577, Pathology Department, Faculty of Veterinary Medicine, , Kafrelsheikh University, ; Kafr Elsheikh, 33516 Egypt
                [6 ]Biochemistry Department, Faculty of Veterinary Medicine, Matrouh University, Matrouh, Egypt
                [7 ]GRID grid.7776.1, ISNI 0000 0004 0639 9286, Pharmacology Department, Faculty of Veterinary Medicine, , Cairo University, ; Giza, 12211 Egypt
                Article
                93196
                10.1038/s41598-021-93196-7
                8263713
                34234176
                a7eb8b84-f900-47a1-8b5f-36eba1f71799
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 February 2021
                : 8 June 2021
                Categories
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                © The Author(s) 2021

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                drug discovery,nephrology
                Uncategorized
                drug discovery, nephrology

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