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      Ameliorative Effect of Graviola ( Annona muricata) on Mono Sodium Glutamate-Induced Hepatic Injury in Rats: Antioxidant, Apoptotic, Anti-inflammatory, Lipogenesis Markers, and Histopathological Studies

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          Abstract

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          Food additives, especially monosodium glutamate (MSG), induces serious liver disorders. This study premeditated to investigate the effect of Graviola extract (GE) on hepatic and cellular alterations induced by MSG. Our result revealed that GE administration normalized the oxidative stress markers, as well as the proinflammatory cytokines, in addition to downregulation of the inducible nitric oxide synthase (iNOS) and FAS, hepatic fatty acid synthase, and led to the upregulation of the silent information regulator protein one (SIRT1) gene. This is the first report investigating the intracellular pathway and mechanism of Graviola extract’s action in alleviating the MSG supplementation injuries.

          Abstract

          Monosodium glutamate (MSG) is a widely used food additive, and there is a trepidation that MSG plays a critical role in multiple hepatic disorders. This study was planned to investigate Graviola extract (GE) effects on hepatic and cellular alterations induced by MSG. Fifty Wistar rats were randomly allocated into five groups: control (received normal saline), Graviola (received 200 mg/kg body weight), MSG (received 2.4 gm MSG/kg, 15% of Lethal dose (LD 50) of MSG), Graviola + monosodium glutamate (MSG + GE; received GE, 200 mg/kg/day and MSG 2.4 gm/kg body weight (BW) for the next four weeks), and monosodium glutamate + Graviola (received MSG only (2.4 gm/kg BW) daily for four weeks, then concomitant with Graviola (200 mg/kg BW) daily for the next four weeks. MSG and GR were administered orally for eight weeks. Our results showed that MSG caused a significant increase in oxidative stress markers malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), hydrogen peroxide (H 2O 2 ), proinflammatory cytokines interleukin 6 (IL-6) level, a tumor protein (P53), hepatic cellular damage, as well as proapoptotic markers caspase-3, and B-cell lymphoma 2 (BCL-2)-like protein 4 (Bax). A significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH), and an antiapoptotic agent B-cell lymphoma 2 (BCl-2) was observed. The detected MSG effects were normalized by Graviola administration, either a prophylactic or protecting dose. Besides, Graviola reduced the expression of inducible nitric oxide synthase (iNOS) and hepatic fatty acid synthase (FAS) and led to the upregulation of the silent information regulator protein one gene expression gene (SIRT1).In conclusion, the results suggest that Gaviola’s interrelated antiapoptotic, antioxidant, and anti-inflammatory properties are potential mechanisms to enhance hepatic deficits and protect the liver. Graviola can, therefore, be considered a promising hepatoprotective supplement. Additionally, further human clinical trials are also necessary to validate the present research.

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              Sirtuins in mammals: insights into their biological function.

              Sirtuins are a conserved family of proteins found in all domains of life. The first known sirtuin, Sir2 (silent information regulator 2) of Saccharomyces cerevisiae, from which the family derives its name, regulates ribosomal DNA recombination, gene silencing, DNA repair, chromosomal stability and longevity. Sir2 homologues also modulate lifespan in worms and flies, and may underlie the beneficial effects of caloric restriction, the only regimen that slows aging and extends lifespan of most classes of organism, including mammals. Sirtuins have gained considerable attention for their impact on mammalian physiology, since they may provide novel targets for treating diseases associated with aging and perhaps extend human lifespan. In this review we describe our current understanding of the biological function of the seven mammalian sirtuins, SIRT1-7, and we will also discuss their potential as mediators of caloric restriction and as pharmacological targets to delay and treat human age-related diseases.
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                Author and article information

                Journal
                Animals (Basel)
                Animals (Basel)
                animals
                Animals : an Open Access Journal from MDPI
                MDPI
                2076-2615
                30 October 2020
                November 2020
                : 10
                : 11
                : 1996
                Affiliations
                [1 ]Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, 33511 Kafrelsheikh, Egypt
                [2 ]Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; elshehawi@ 123456hotmail.com
                [3 ]Department of Genetics, Faculty of Agriculture, Alexandria University, 21527 Alexandria, Egypt
                [4 ]Department of Zoology, Faculty of Science, Mansoura University, 35516 Mansoura, Egypt; wafaa_elkholy2002@ 123456yahoo.com
                [5 ]Department of Anatomy, Faculty of Medicine, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt; Rasha_2002@ 123456yahoo.com
                [6 ]Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Aswan University, 81528 Aswan, Egypt; Hamouda2000@ 123456yahoo.com
                [7 ]Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, 22785 Alexandria, Egypt; hossam.gafar@ 123456yahoo.com
                [8 ]Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Alexandria University, 22785 Alexandria, Egypt; m.abumandour@ 123456yahoo.com
                [9 ]Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Kafrelsheikh University, 33511 Kafrelsheikh, Egypt; foad.farrag@ 123456yahoo.com
                Author notes
                Author information
                https://orcid.org/0000-0003-2722-2466
                https://orcid.org/0000-0003-4357-4904
                https://orcid.org/0000-0002-3289-1982
                https://orcid.org/0000-0002-4048-6717
                Article
                animals-10-01996
                10.3390/ani10111996
                7693810
                33143024
                86e28227-a362-4eaf-8775-490194bd25e5
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2020
                : 25 October 2020
                Categories
                Article

                graviola,liver,monosodium glutamate,antioxidant,apoptosis,inos,sirt1

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