The possible Protective effects of Melatonin and/or Vitamin C on Monosodium Glutamat-induced hippocampal neurotoxicity in male albino rats: a histological and immunohistochemical study

Background: The hippocampus, a key region for learning and memory, is highly susceptible to excitotoxicity from excessive glutamate receptor activation, leading to neuronal injury or death. Monosodium glutamate (MSG), a common food additive, has been associated with various neurotoxic and neurodegenerative effects.Materials and Methods: Adult rats were used to evaluate the protective effects of vitamin C and melatonin against MSG-induced hippocampal damage. Sixty rats were divided into five groups: control, MSG (2 g/kg), VC (MSG + 100 mg/kg vitamin C), ML (MSG + 10 mg/kg melatonin), and ML+VC (MSG + both vitamin C and melatonin). Treatments were administered orally for 28 days. Hippocampal tissues were collected for histological and immunohistochemical analysis of GFAP, TNF-α, and caspase-3 expression. Ethical approval was obtained from the Institutional Animal Care and Use Committee (IACUC) of Benha University, Egypt.Results: MSG exposure significantly increased GFAP, TNF-α, and caspase-3 expression, indicating neuroinflammation, apoptosis, and marked histological alterations in the CA1 region. In the VC group, some pyramidal neurons were distorted with scattered glial cells and vacuolations, whereas in the ML group, pyramidal neurons were more densely packed with minimal glial pyknosis and vacuolations. Combined melatonin and vitamin C treatment largely preserved hippocampal architecture and markedly reduced inflammatory and apoptotic markers.Conclusion: MSG exerts pronounced neurotoxic effects in the rat hippocampus. Co-administration of vitamin C and melatonin produced a synergistic neuroprotective effect, highlighting their potential to mitigate MSG-induced hippocampal damage.