Glycine as a potential neuroprotective adjuvant to reduce cisplatin-induced brain inflammation in mice

BACKGROUND: Cisplatin-induced neurotoxicity is driven in part by neuroinflammation and oxidative injury in vulnerable brain regions. Glycine has anti-inflammatory and antioxidant properties that may offer neuroprotection against chemotherapy-related brain damage. METHODS: Twenty-five adult male BALB/c mice were randomized into five groups (n = 5/group) Group 1 received cisplatin for 14 days; Group 2 received cisplatin plus glycine for 14 days; Group 3 received cisplatin for 28 days; Group 4 received cisplatin for 14 days followed by glycine for 14 days; and Group 5 received cisplatin for 28 days with glycine introduced from day 14 to day 28. Cisplatin was administered intraperitoneally at 3 mg/kg every fourth day, and glycine was given subcutaneously at 1 g/kg daily. The primary outcome was serum TNF-α measured by ELISA. Secondary outcomes were neuronal integrity and optical density in the hippocampus and frontal cortex assessed by Nissl staining. Data were analyzed using one-way ANOVA with Tukey post-hoc testing. RESULTS: Serum TNF-α levels differed significantly among groups (F = 230.422, p < 0.001). Mean TNF-α concentrations were 150.0 pg/mL in Group 1, 130.2 pg/mL in Group 2, 201.4 pg/mL in Group 3, 159.4 pg/mL in Group 4, and 171.0 pg/mL in Group 5. Prolonged cisplatin exposure (Group 3) produced the highest TNF-α levels, whereas concurrent glycine administration during the 14-day regimen (Group 2) resulted in the lowest levels. Compared with the 28-day cisplatin group, both delayed glycine treatment (Group 4) and glycine introduced during the second half of cisplatin exposure (Group 5) were associated with lower TNF-α concentrations. Histological analysis demonstrated reduced Nissl staining intensity and neuronal preservation in cisplatin-only groups, particularly Group 3, whereas glycine-treated groups showed better preservation of neuronal architecture and optical density in the hippocampus and frontal cortex. CONCLUSION: Glycine attenuated cisplatin-induced neuroinflammation and preserved neuronal integrity in the hippocampus and frontal cortex of mice. These findings support further preclinical evaluation of glycine as a low-cost adjuvant strategy to reduce chemotherapy-associated neurotoxicity.