Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Therefore, the present study designed to investigate the probable protective role of melatonin against VPA-induced liver toxicity. For that purpose, 28 Wistar rats were randomly selected and divided into four groups, namely the Group C (vehicle), VPA (500 mg/kg/day VPA), MEL + VPA (10 mg/kg/day melatonin + 500 mg/kg/day VPA) and MEL (10 mg/kg/day melatonin). The agents were given by oral gavage for 14 days. Blood and liver tissue samples from all the rats were harvested on the 15th day of experiment. Biochemical analyses were conducted on the blood samples. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), alpha glutathione S-transferases (α-GST), nuclear factor-κB (NF-κB), myeloperoxidase (MPO) and changes in gene expression were examined in the liver tissues. Also, liver histopathological analyses were conducted. VPA administration significantly increased the levels of α-GST, MDA, NF-κB and of IL-1β, TNF-α gene expression in the liver compared to Group C. Moreover, vacuolization, hydropic degeneration, inflammatory cell infiltration, and sinusoidal congestion were commonly detected in the VPA-treated group along with the highest apoptotic index (TUNEL staining) values. Melatonin administration was revealed to exhibit powerful protective properties at cellular, inflammatory and oxidative level activities against VPA-induced liver toxicity. Therefore, melatonin administration may be used as an adjuvant therapy against to VPA-induced liver toxicity.

中文翻译：

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褪黑素改善了丙戊酸钠对大鼠的肝毒性

丙戊酸（VPA）是一种抗惊厥和情绪稳定剂，用于治疗所有年龄段的患者的癫痫病。但是，它会随着氧化应激的增加而引起肝毒性。褪黑激素（MEL）被称为抗氧化剂和抗炎剂。因此，本研究旨在研究褪黑激素对VPA诱导的肝毒性的可能保护作用。为此目的，随机选择了28只Wistar大鼠并将其分为四组，即C组（车辆），VPA（500 mg / kg /天VPA），MEL + VPA（10 mg / kg /天褪黑激素+ 500 mg /公斤/天VPA）和MEL（10毫克/公斤/天褪黑激素）。通过口管给予药剂14天。在实验的第15天收集所有大鼠的血液和肝组织样品。对血样进行生化分析。丙二醛（MDA）含量，检查肝组织中的超氧化物歧化酶（SOD），α谷胱甘肽S-转移酶（α-GST），核因子-κB（NF-κB），髓过氧化物酶（MPO）和基因表达的变化。另外，进行了肝组织病理学分析。与C组相比，VPA给药显着增加了肝脏中α-GST，MDA，NF-κB和IL-1β，TNF-α基因表达的水平。此外，空泡化，水肿性变性，炎性细胞浸润和正弦窦充血通常在VPA治疗组中检测到，同时具有最高的凋亡指数（TUNEL染色）值。褪黑激素的给药显示出对VPA诱导的肝毒性在细胞，炎症和氧化水平上具有强大的保护作用。因此，