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      Modulatory influence of Acacia hydaspica R. Parker ethyl acetate extract against cisplatin inveigled hepatic injury and dyslipidemia in rats

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          Abstract

          Background

          Cisplatin (CP) is recommended as a first-line chemotherapeutic agent for solid tumors, however its usage outcomes in severe adverse effects. Acacia hydaspica possesses various phytochemicals and pharmacological activities. The current study aimed to investigate the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP induced aberrations in lipid profile and hepatotoxicity.

          Methods

          Rats were randomly separated into six groups ( n = 6). Group 1 (control) received distilled water orally for 21 days. Groups 2 (CP control) received a single dose of CP (7.5 mg/kg bw, i.p) on day 16, group 3 (Plant control) received AHE (400 mg/kg b.w, oral) for 21 days, group 4 (post treated group); CP received on day 16 and AHE (400 mg/kg b.w/day, p.o.) was administered after CP till day 21, Group 5 (pretreated group) received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16, group 6 (Silymarin + CP) received 100 mg/kg b.w., p.o. (11 doses/21 days) and CP (7.5 mg/kg b.w., i.p.) on day 16. Lipid profile, liver functional tests, oxidative stress markers, antioxidant enzymes status and histopathological changes were examined.

          Results

          The present study revealed that CP caused body weights loss and increase liver index. CP significantly increased serum total lipid, triglycerides and LDL-cholesterol levels. Conversely, it significantly decreased serum HDL-cholesterol level. CP induced marked deteriorations in serum liver function biomarkers, reduced antioxidant enzymes in tissue, while elevated tissue oxidative stress markers along with morphological injuries compared to control rats. Treatment with AHE ameliorated CP induced alterations in lipid profile, serum ALT, AST, ALP and total bilirubin levels and liver weight. Furthermore AHE treatment improved the total protein and antioxidant enzymes levels while decreased the level of MDA, H 2O 2, and NO. The altered parameters were returned to the control level with AHE pretreatment. Histopathological analysis also supported the biochemical findings. Pretreatment seems to be more effective compared to post treatment indicating protective effect.

          Conclusion

          These results reveal that treatment of AHE may be useful in the prevention of CP induced hepatotoxicity due to its antioxidant potential and polyphenolic constituents.

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          Most cited references49

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          Drug-induced hepatotoxicity.

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            Oxidative stress-related molecules and liver fibrosis.

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              Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity.

              cis-Diamminedichloroplatinum (II) (cisplatin) is an important chemotherapeutic agent useful in the treatment of several cancers; however, it has several side effects such as nephrotoxicity. The role of the oxidative and nitrosative stress in cisplatin-induced nephrotoxicity is additionally supported by the protective effect of several free radical scavengers and antioxidants. Furthermore, in in vitro experiments, antioxidants or reactive oxygen species (ROS) scavengers have a cytoprotective effect on cells exposed to cisplatin. Recently, the participation of nitrosative stress has been more explored in cisplatin-induced renal damage. The use of a water-soluble Fe(III) porphyrin complex able to metabolize peroxynitrite (ONOO(-)) has demonstrated that this anion contributes to both in vivo and in vitro cisplatin-induced toxicity. ONOO(-) is produced when nitric oxide (NO*) reacts with superoxide anion (O(2)(*-)); currently, there are evidences suggesting alterations in NO* production after cisplatin treatment and the evidence appear to NO* has a toxic effect. This article goes through current evidence of the mechanism by more than a few compounds have beneficial effects on cisplatin-induced nephrotoxicity, contribute to understanding the role of oxidative and nitrosative stress and suggest several points as part of the mechanism of cisplatin toxicity.
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                Author and article information

                Contributors
                tayyaba_sona@yahoo.com
                +923005189624 , ruhail12345@yahoo.com
                aalmajwal@ksu.edu.sa
                mrkhanqau@yahoo.com
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                12 June 2017
                12 June 2017
                2017
                : 17
                : 307
                Affiliations
                [1 ]ISNI 0000 0001 2215 1297, GRID grid.412621.2, Department of Biochemistry, Faculty of Biological Sciences, , Quaid-i-Azam University, ; Islamabad, Pakistan
                [2 ]ISNI 0000 0001 2215 1297, GRID grid.412621.2, Department of Animal Sciences, Faculty of Biological Sciences, , Quaid-i-Azam University, ; Islamabad, Pakistan
                [3 ]ISNI 0000 0004 1773 5396, GRID grid.56302.32, Department of Community Health Sciences, College of Applied Medical Sciences, , King Saud University, ; Riyadh, Kingdom of Saudi Arabia
                Article
                1824
                10.1186/s12906-017-1824-y
                5469132
                cf1825cd-80ee-4baf-b646-bd193c34336d
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 March 2017
                : 6 June 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Complementary & Alternative medicine
                cisplatin,lipid profile,antioxidant,oxidative stress,liver fibrosis,hepatotoxicity

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