本研究旨在研究达格列净和水飞蓟素单独和联合对抗四氯化碳(CCl4)诱导的肝毒性和预期机制的保肝潜力。将30只雌性Wistar大鼠随机分为5组。除正常对照(组I)外,所有实验动物均给予CCl4。此外,第二组,III,IV,和V用阿拉伯胶处理,水飞蓟素,dapagliflozin,达格列净和水飞蓟素的组合,分别,14天。Dapagliflozin,单独的水飞蓟素,结合起来,显著降低(P<0.05)血清ALT水平,AST,AST:ALT比值,和总胆红素与CCl4中毒的对照大鼠相比。IL-1β水平显著降低(p<0.05),IL-6,TNF-α,亚硝酸盐,和4-羟基壬烯醛,伴随着过氧化氢酶的升高,超氧化物歧化酶,谷胱甘肽过氧化物酶,核红系2相关因子2(Nrf2),达格列净处理组肝匀浆中血红素加氧酶-1(HO-1),单独的水飞蓟素,结合起来,与CCl4中毒对照组相比。达格列净与水飞蓟素组合显示出协同的肝保护作用。我们的研究揭示了dapagliflozin单独和与水飞蓟素组合在CCl4中毒的Wistar大鼠中通过调节Nrf2和HO-1信号通路具有深远的保肝潜力。
This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways.