Protective Effect of L‐Arginine and Filgrastim Against Valproic Acid–Induced Histopathological Changes on the Gastric and Lingual Mucosa

Valproic acid (VPA) is a commonly used anticonvulsant prescribed for various neurological disorders. Adverse effects may arise from chronic use and high dosages. This study aims to evaluate the protective effects of L-arginine and Filgrastim against the harmful impact of VPA on gastric and lingual mucosa. Forty male albino rats were divided into four groups (10 for each). The control group received saline, while the VPA group administered VPA (500 mg/kg) orally for 14 days. The VPA + L-arginine and VPA + Filgrastim groups received L-arginine (300 mg/kg) and Filgrastim (40 μg/kg), respectively, starting 3 days prior to VPA administration and continued concurrently with VPA for 14 days. Results revealed that VPA caused a decrease in gastric and lingual malondialdehyde (MDA) and superoxide dismutase (SOD) levels, tissue damage, and ulceration in the gastric mucosa. Lingual papillae appeared atrophied. A significant reduction in gastric mucosal thickness, parietal cell number, and fungiform papillae height was found, while the fungiform papillae width was significantly increased. Increased caspase-3 reaction in the parietal and chief cells of the gastric mucosa, as well as in the filiform and fungiform papillae of the tongue, was observed. The VPA + L-arginine and VPA + Filgrastim groups showed improvement in gastric and tongue biochemical and histological abnormalities, with a marked decrease in the caspase-3 reaction in gastric tissue. In the VPA + Filgrastim group, only the tongue tissue showed decreased caspase-3 reaction. It can be concluded that L-arginine and Filgrastim demonstrated effective protection of gastric and lingual mucosa against VPA-induced damage.