Hepatotoxicity of Monoglutamate Sodium: Oxidative Stress and Histopathlogical Study
Authors: Elshafey Mohamed , Eladl Mohamed Ahmed , El‐Sherbiny Mohamed , Atef Hoda , El Morsi Doaa A. 
Published: November 2023

Introduction

Monosodium glutamate (MSG) is commonly used to increase palatability of food. It is thus reportedly permitted as a safe food additive that needs no specified average daily intake or an upper limit intake requirement. Moreover, it occurs naturally in various foods including cheeses, seafood, poultry and vegetables. Despite there is no problem if MSG is consumed in small amounts in one food, yet the problem is present if small amounts are consumed daily in different foods. However, several studies in animals have shown that MSG is toxic to various organs such as the liver, brain, thymus and kidneys. Decreased levels of major anti‐oxidant enzymes and increased lipid peroxidation have been demonstrated in the kidneys of chronic MSG‐exposed rats

The aim of the present work is to study the hepatotoxic effect of MSG as regard histopathological and electron microscopy changes and wheather these changes were due to oxidative stress effect.

Materials and Methods

Thirty six adult male rats were divided into three groups (12/group): Group I (Control group): Rats were given daily oral dose of distilled water at a dose of 4 mL/Kg for 90 days. Group II (Test group): Rats were treated with daily oral dose of MSG at a dose of 4 mg/Kg for 90 days. Group III (Recovery group): Rats received the same dose as group II then kept four weeks later with water only to study the effect of withdrawal. At the end of the experimental period (90 days), blood samples were taken by cardiac puncture to measure liver enzymes; Alanine transaminase (ALT) and aspartate amino transaminase (ASAT). The excised liver was taken, divided and prepared to measure the products of oxidative stress (Hepatic malondialdhyde (MDA), Hepatic superoxide dismutase (SOD), Glutathione S‐transferase (GST)) and examined for histopathological (H&E, Masson's Trichome stain); immunohistochemistry for cleaved caspase‐3 and transmission electron microscope changes.

Results

There were high significant differences in all parameters in the group treated with MSG than the control group regarding liver enzymes and parameters of oxidative stress. Most of the hepatocytes in MSG group, showed macrovesicular, panacinar hepatic steatosis and was complicated by presence of Mallory bodies (Figure 1). Score 3 in modified HAI grading scores for necrosis and inflammation. Extensive fibrosis was seen around the central vein and extending into the walls of the sinusoids in MSG group compared to other groups. Caspase 3 immunoreactivity was positive in MSG group, which could be seen around central vein, in the cell fibrous bands in the wall of sinusoids and in the necro‐inflammatory areas; furthermore, the apoptosis was markedly decreased in the recovery group. The Ultrastructural changes was more evident in MSG group in the form of irregular nuclei, increased lipid droplets, abundant rough endoplasmic reticulum and numerous swollen mitochondria, widened gap junctions and increased fibrillary deposition (Figure 2).

Conclusions

Reduced antioxidant enzymes, increased lipid peroxidation, and fibrosis brought on by high MSG intake strongly support the theory that oxidative stress is central to MSG‐induced hepatic toxicity. These results take on considerable significance in light of the widespread usage of dietary MSG and it is highly suggested that MSG should have its safety profile re‐examined and be potentially withdrawn from the food chain.