ArticleJournal of clinical practice and research2026
Neuroprotective and Nitric Oxide-Modulating Effects of D-Limonene in a Penicillin-Induced Epilepsy Model in Rats.
Article in Journal of clinical practice and research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: Epilepsy involves dysregulated inflammatory pathways and oxidative stress (OS). Nitric oxide (NO), an endogenous vasodilator, may exert neurotoxic effects under OS. D-limonene, a monoterpene with antioxidant and anti-inflammatory properties, can modulate these processes. This study addressed the neuroprotective effects of D-limonene by assessing its influence on NO levels in serum and brain tissue and its interaction with sodium valproate (VPA) in a penicillin-induced epilepsy model in rats. Materials and Methods: Thirty-five male Wistar albino rats (12-16 weeks, 200±50 g) were clustered into 5 groups (n=7): control (penicillin 500 IU, 2.5 µL, i.c.); D-limonene 50 mg/kg + penicillin 500 IU; D-limonene 100 mg/kg + penicillin 500 IU; VPA 300 mg/kg + penicillin 500 IU; and combination (D-limonene 100 mg/kg + VPA 300 mg/kg + penicillin 500 IU). Treatments were administered intraperitoneally. NO levels were determined using a commercial colorimetric assay kit. Data were analyzed using one-way ANOVA followed by Sidak's multiple comparisons test and are presented as mean±SD, with statistical significance set at p<0.05. Results: Serum NO peaked in the penicillin group (568.0±84.95 µmol/L) and decreased dose-dependently with D-limonene (490.5±86.12; 347.6±25.39 µmol/L). VPA further reduced NO (259.0±20.04 µmol/L), whereas the combination modestly increased it (390.6±74.95 µmol/L). Tissue NO showed a similar trend, with the lowest level observed with VPA (120.4±12.60 µmol/L) and partially restored by combination treatment (168.8±20.85 µmol/L). Conclusion: D-limonene reduced NO levels dose-dependently. VPA had a stronger inhibitory effect, whereas their combination attenuated this inhibition, suggesting that D-limonene may modulate NO metabolism and confer neuroprotection in experimental epilepsy.
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