Modulation of Synaptophysin Immunoreactivity, Oxidative Stress Markers, and Cerebral Cortex Toxicity: The Role of Magnesium Glycinate in Cyclophosphamide-Treated Rats
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Abstract
Background: The usage of cyclophosphamide (CP) in chemotherapy is limited by neurotoxicity, anxiety-related behaviours, and cognitive dysfunction. Its shortcomings in this regard have prompted the search for substances that can ameliorate the adverse effects without compromising its usage in cancer management. This study investigated whether magnesium glycinate (MgGly) attenuates CP-induced anxiety-like behaviour, oxidative stress, and cortical degeneration in Wistar rats.
Methods: Forty-eight male rats (n=8/group) were divided into: control, low-dose MgGly (22.8 mg/kg), high-dose MgGly (32.8 mg/kg), CP + low-dose MgGly, CP + high-dose MgGly, and CP-only. CP (150 mg/kg, i.p.) was given on days 1, 3, and 5; MgGly was administered orally for 21 days. We evaluated neurobehaviour, cerebral oxidative stress (measured by MDA, TAC, SOD, and CAT), cortical cytoarchitecture, and synaptophysin immunoreactivity.
Results: CP intoxication resulted in severe anxiety and motor deficits, significantly reducing open-arm time and line crossing. Biochemically, CP elevated cerebral MDA levels and depleted SOD, TAC, and CAT activities, inducing profound cortical degeneration and synaptic stripping. High-dose MgGly (32.8 mg/kg) significantly reversed these impacts, restoring open-arm time, attenuating MDA (0.68±0.02 µM), and recovering SOD (0.38±0.02 U/ml), TAC (5.83±0.41 mM), and CAT (1.02±0.05 U/mg). It also robustly preserved cortical architecture and synaptophysin immunoreactivity. Protective effects were strictly dose-dependent, favouring the 32.8 mg/kg regimen. MgGly alone lacked toxicity.
Conclusion: This study demonstrated that magnesium glycinate confers robust, dose-dependent neuroprotection against CP-induced oxidative stress, neurotoxicity, cortical degeneration, and a mechanistically supported and clinically accessible adjunct to mitigate chemotherapy-related neurocognitive and neurodegenerative impacts.
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