Sodium valproate (VPA) is a widely used antiepileptic drug associated with hepatotoxicity. Safranal, a bioactive compound derived from saffron, possesses hepatoprotective properties. This study aimed to investigate the protective effects of safranal against VPA-induced liver injury in rats. Rats were administered VPA to induce hepatotoxicity and concurrently or subsequently treated with safranal.

Liver function biomarkers, histopathological examination, oxidative stress markers, apoptotic parameters, and gene expression analysis were evaluated. VPA significantly elevated liver enzymes, induced histopathological changes, and increased oxidative stress and apoptosis. Safranal pretreatment or post-treatment significantly ameliorated VPA-induced liver injury, as evidenced by improved liver function tests, reduced histopathological alterations, and decreased oxidative stress and apoptosis.

Mechanistically, safranal modulated the expression of genes involved in hepatoprotection, inflammation, and oxidative stress. These findings suggest that safranal possesses hepatoprotective potential against VPA-induced liver injury by mitigating oxidative stress, apoptosis, and modulating gene expression. Further studies are warranted to elucidate the underlying molecular mechanisms and explore the clinical application of safranal in VPA-associated liver toxicity.

Sodium valproate (SV) is a commonly used antiepileptic drug known for its efficacy but often associated with hepatotoxicity, posing a significant clinical challenge. This study investigates the therapeutic potential of safranal, a bioactive component of saffron, in mitigating SV-induced liver toxicity in a rat model, focusing on its effects on gene expression, oxidative stress parameters, and apoptosis.

Male Wistar rats were divided into four groups: control, SV-treated (500 mg/kg), safranal-treated (50 mg/kg), and SV + safranal co-treated groups. Liver toxicity was induced by SV administration for 21 days, followed by safranal treatment for an additional 14 days. Liver function tests, histopathological examinations, and molecular analyses were conducted to evaluate the protective effects of safranal.

Safranal administration significantly ameliorated SV-induced liver damage as evidenced by reduced serum levels of liver enzymes (ALT, AST) and improved histological architecture compared to the SV-treated group. Safranal attenuated oxidative stress by enhancing antioxidant enzyme activities (superoxide dismutase, catalase) and reducing lipid peroxidation levels. Furthermore, safranal modulated SV-induced alterations in gene expression, particularly those involved in apoptosis (Bax, Bcl-2 ratio) and inflammation (TNF-α, IL-6), thereby exerting anti-apoptotic and anti-inflammatory effects.

This study provides mechanistic insights into the protective effects of safranal against SV-induced liver toxicity, highlighting its potential therapeutic utility. Safranal's ability to mitigate oxidative stress, regulate gene expression related to apoptosis and inflammation, and preserve liver function underscores its promising role as a hepatoprotective agent. Further research is warranted to elucidate the full spectrum of safranal's molecular mechanisms and its clinical implications in managing drug- induced liver injuries.

Safranal, sodium valproate, liver toxicity

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