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

Mustafa Shukry,Hazem S Hamoda,Hossam G Tohamy,Rasha A Elsisy,Foad A Farrag,Mohamed M Abumandour,Wafaa M El-Kholy,Ahmed M El-Shehawi

doi:10.3390/ani10111996

Abstract

Simple SummaryFood 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.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 (LD50) 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 (H2O2), 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.

Highlights

Many synthetic contaminants, such as industrial toxins and food additives, have been implicated in adverse effects
At the end of the experiment (56 days), body weight was found to increase significantly in the monosodium glutamate (MSG)-treated group compared to the control group (p < 0.05)
2020, 10, in x rats orally administered MSG + Graviola extract (GE) and GE + MSG compared to the MSG-treated group.Concerning control one, there were no significant shifts with the Graviola treatment. (Figure 2)

Summary

Introduction

Many synthetic contaminants, such as industrial toxins and food additives, have been implicated in adverse effects. Some food additives act as either preservatives or palatability enhancers. One such food additive is monosodium glutamate (MSG). MSG is one of these food additives that is openly used as a flavor enhancer. It is glutamic acid salt [1]. It is documented that rats administrated MSG encountered many disorders such as gonadal dysfunction, an increase in stomach cancer incidence, brain damage, learning difficulty, and depletion in some neurotransmitters in the hypothalamus region [2]. MSG enhances meals’ palatability and significantly improves the appetite center and, increases body weight [5]. MSG enhances flavor stimulation and boosts appetite, it is considered toxic to humans and experimental animals [6]. Glutamate has a very low acute toxicity; the oral dose lethal to LD50 in rats and mice is ∼15,000–18,000 mg/kg body weight, respectively [7]

Results

Discussion

Conclusion