Abstract
BACKGROUND: Excessive and prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause hepatotoxicity. However, prevention and treatment of this complication remain challenging. OBJECTIVES: This study investigated the potential of the hydroalcoholic extract of Dracocephalum kotschyi (HEDK) in inhibiting diclofenac (DIC)-induced hepatotoxicity in rats. METHODS: Forty-two male Wistar rats were divided into six groups: Control group, DIC group, DIC+HEDK group in three different doses, and DIC+silymarin (SLY) group. The rats were treated for 7 days. Then, by inducing anesthesia, collecting blood from the heart, and isolating the liver, the effects of HEDK were evaluated by measuring the liver enzymes, antioxidant enzymes (using the calorimetric method), and inflammatory factors (using the RT-PCR method). Histopathological changes of the liver were also studied. RESULTS: The DIC significantly increased the levels of enzymes in the liver, such as ALT, AST, and ALP, lipid oxidation product, malondialdehyde (MDA), and cytokines, interleukin 1 beta (IL-1β), tumor necrosis factor α (TNF-α), NOD-like receptor protein 3 (NLRP3), and high-mobility group box 1 (HMGB1). It also decreased the levels of oxidative stress factors, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Treatment with HEDK improved the liver's biochemical parameters and significantly reduced the inflammatory cytokines. With the reduction of MDA, antioxidant enzymes also increased. The liver's histological study showed the ameliorating effects of HEDK. CONCLUSIONS: The HEDK provided significant protection against DIC-induced toxicity due to its antioxidant effects and inhibition of inflammatory factors.