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      Neuroprotective effect of N-acetylcysteine against cisplatin-induced toxicity in rat brain by modulation of oxidative stress and inflammation

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          Abstract

          Background

          Neurotoxicity is a major obstacle to the effectiveness of cisplatin (CDDP) in cancer chemotherapy. Oxidative stress and inflammation are considered to be the major mechanisms involved in CDDP-induced neurotoxicity. The rationale of our study was to investigate the efficacy of N-acetylcysteine (NAC) at two different doses in the management of CDDP-induced toxicity in rat brain by monitoring its antioxidant and anti-inflammatory effects.

          Methods

          Thirty-five male rats were divided into five groups (n=7) as follows: control group (0.5 mL saline), NAC 100 group (100 mg/kg), CDDP group (8 mg/kg), NAC 50-CDDP group (50 mg/kg NAC and 8 mg/kg CDDP), and NAC 100-CDDP group (100 mg/kg NAC and 8 mg/kg CDDP). NAC was administered for 20 consecutive days, while CDDP was injected once on day 15 of the treatment protocol.

          Results

          The neurotoxicity of CDDP was evidenced by a marked increase in acetylcholinesterase and monoamine oxidase activities. It also induced oxidative stress as indicated by increased levels of lipid peroxidation, nitric oxide, and protein carbonyl with a concomitant decline in reduced glutathione, glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase in the brain. Moreover, CDDP enhanced the synthesis of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. Treatment with NAC at the two selected doses significantly attenuated CDDP-induced changes in the brain cholinergic function, improved the brain oxidant/antioxidant status, and also reversed the overproduction of pro-inflammatory cytokines in brain and serum.

          Conclusion

          NAC could serve as an appropriate and safe complementary therapeutic agent to attenuate the toxicity of CDDP in the brain and therefore improve its outcomes in chemotherapy.

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          Most cited references 36

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          Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids.

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            Determination of carbonyl content in oxidatively modified proteins.

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              A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates.

              1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS.+ radical cation. 2. An automated method for use on a centrifugal analyser, as well as a manual method, is described. 3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard. 4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated. 5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2019
                11 April 2019
                : 13
                : 1155-1162
                Affiliations
                [1 ]Department of Zoology, Faculty of Science, University of Alexandria, Alexandria, Egypt, wmwahab@ 123456iau.edu.sa
                [2 ]Department of Basic Sciences/Biology Unit, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahaman Bin Faisal University, Dammam, Saudi Arabia, wmwahab@ 123456iau.edu.sa
                Author notes
                Correspondence: Wessam M Abdel-Wahab, Department of Basic Sciences/Biology Unit, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahaman Bin Faisal University, Po Box 2114, Dammam 31451, Saudi Arabia, Tel +966 56 412 4233, Fax +966 3857 5307, Email wmwahab@ 123456iau.edu.sa
                Article
                dddt-13-1155
                10.2147/DDDT.S191240
                6469471
                © 2019 Abdel-Wahab and Moussa. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                rats, n-acetylcysteine, brain, neurotoxicity, cisplatin

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