Table 4.

Summary of preclinical studies associating MSG exposure with hepatic toxicity

Mode of administration	Species	MSG dosage/day	Duration of administration (days)	MSG effect (vs. control)	Reference
Mixed with diet	Wistar rats	0.04 mg/kg (n=8) 0.08 mg/kg (n=8)	42	Morphological changes: dilated central veins, cyto-architectural distortions of the hepatocytes, centrilobular hemorrhagic necrosis; Biochemical changes: increase in total protein, albumin, aspartate transaminase, and alanine transaminase activities; Changes were dose-dependent.	(Eweka et al., 2011)
Mixed with diet	Adult male Rattus norvigicus	6 g/kg	45	Central veins dilations, severe cyto-architectural distortions of the hepatocytes, vacuolated cytoplasm, swollen mitochondria and vesiculated rough endoplasmic reticulum with picknotic nuclei; Collagen deposition and connective tissue fiber impairment in the hepatocytes, together with severe reduction of mucopolysaccharide content; Increase of the expression of ki-67 and p53 pro-apoptotic proteins in hepatocytes.	(El-Meghawry El-Kenawy et al., 2012)
Oral	Male Wistar Rats	8 g/kg (n=6)	20	Increased lipid peroxides in liver, kidney, and serum; Diminished reduced glutathione in serum, liver, and kidney; Increased triglycerides, total cholesterol, urea; Morphological changes in liver (central venous congestion, diffuse degeneration, necrosis of hepatocytes) and kidney (cortical tubular degeneration).	(Paul et al., 2012)
Oral	Male Wistar Rats	0.6 g/kg (n=6)	10	Increased lipid peroxidation and the activities of glutathione-S-transferase, catalase, superoxide dismutase in the liver; Decreased reduced glutathione level in the hepatocytes; Increased activities of aspartate transaminase, alanine transaminase and gamma glutamyl transferase.	(Onyema et al., 2006)
Subcutaneous	Newborn C57BL/6J male mice	4 g/kg (n=6)	Single dose administration within 5 days of their birth	Characteristic liver histopathology of nonalcoholic steatohepatitis. Metabolic syndrome-like features: Increase in serum levels of insulin and cholesterol; Microvesicular steatosis and inflammatory cell infiltration in the liver; Enlarged adipocytes and crown-like structures in the epididymal fat; Increased frequencies of monocytes and M1 macrophages in the liver and epididymal fat tissue;	(Takai et al., 2014)
Subcutaneous	ICR male mice	2 g/kg (n=36) associated with unrestricted (n=18) or restricted dietary regimens (n=18)	From birth to day 5 of life	Obesity, increased adiposity in the absence of hyperphagia, hyperinsulinemia; Increase in triglycerides, LDL-chlesterol and alanine transaminase activity after 6 months for both groups. Reversible at month 12 for group receiving MSG and restricted dietary regimen; After 6 months, major liver steatosis, but no fibrosis, for both MSG groups. At 12 months of age, the MSG-unrestricted mice, but not those with restricted diet, had mild fibrosis with steatohepatitis and liver nodules.	(Fujimoto et al., 2014)
Intraperitoneal	Male albino Wistar-Norwegian brown hybrid rats	4 g/kg	10	Significant increase of lipid peroxidation and of glutathione-S-transferase activity in liver, kidney, brain of rats; Decrease of glutathione level in the liver, kidney and brain; Increased catalase and superoxide dismutase activities in liver, decreased their activities in kidney and brain; Increased activity of aspartate transaminase, alanine transaminase and gamma glutamyl transferase.	(Farombi & Onyema, 2006)