Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 82817, Saudi Arabia.
Pharmaceutical Science in Applied Toxicology, College of Pharmacy, Jazan University, Jazan 82817, Saudi Arabia.
Molecules. 2023 Jan 16;28(2):881. doi: 10.3390/molecules28020881.
This study investigated the potential hepatoprotective activity of curcumin-incorporated nano-lipid carrier (Cur-NLC) against cypermethrin (Cyp) toxicity in adult Wistar male rats. All animals in groups III, IV, V, and VI were subjected to Cyp (50 mg/kg) toxicity for 15 days. Three different doses of Cur-NLC (1, 2.5, and 5 mg/kg/day) were administered orally for 10 days. The toxic effects were evaluated considering the increases in serum hepatic biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein and albumin, and lipid peroxidation (LPO), as well as a decrease in antioxidative activity (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase) and the upregulation of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Immunohistochemistry studies of proteins (NF-κB, Apaf-1, 4-HNE, and Bax) showed enhanced expression, and histopathological examination revealed architectural changes in liver cells, indicating liver toxicity in animals. Toxicity was determined by quantitative and qualitative determinations of DNA fragmentation, which show massive apoptosis with Cyp treatment. The administration of Cur-NLC significantly ameliorates all changes caused by Cyp, such as a decrease in the levels of serum liver markers, an increase in antioxidative parameters, a decrease in expression of inflammatory cytokines (IL-1β, IL-6, TNF-α, and NF-κB), and apoptosis (caspases-3, 9, Apaf-1, 4-HNE, and Bax), according to calorimetric and immunohistochemistry studies. The smear-like pattern of DNA is ameliorated similarly to the control at a high dose of Cur-NLC. Furthermore, all histopathological changes were reduced to a level close to the control. In conclusion, Cur-NLC could be a potent nutraceutical that exhibits a hepatoprotective effect against Cyp-induced hepatotoxicity in rats.
本研究旨在探讨姜黄素纳米脂质载体(Cur-NLC)对成年雄性 Wistar 大鼠体内氯菊酯(Cyp)毒性的潜在肝保护活性。第 III、IV、V 和 VI 组所有动物均接受 Cyp(50mg/kg)毒性 15 天。三种不同剂量的 Cur-NLC(1、2.5 和 5mg/kg/天)连续口服 10 天。通过评估血清肝生物标志物丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总蛋白和白蛋白的升高以及脂质过氧化(LPO)的降低,同时评估抗氧化活性(还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶)的降低和炎症细胞因子(IL-1β、IL-6 和 TNF-α)的上调,来评估毒性作用。蛋白质(NF-κB、Apaf-1、4-HNE 和 Bax)的免疫组织化学研究显示表达增强,组织病理学检查显示肝细胞结构改变,表明动物肝脏毒性。通过定量和定性测定 DNA 片段的碎裂来确定毒性,结果显示 Cyp 处理后大量细胞凋亡。Cur-NLC 的给药可显著改善 Cyp 引起的所有变化,如血清肝标志物水平降低、抗氧化参数增加、炎症细胞因子(IL-1β、IL-6、TNF-α和 NF-κB)表达降低以及细胞凋亡(caspases-3、9、Apaf-1、4-HNE 和 Bax)减少。根据比色法和免疫组织化学研究,高剂量 Cur-NLC 可改善 DNA 的类似涂片模式。此外,所有组织病理学变化均减少到接近对照的水平。综上所述,Cur-NLC 可能是一种有效的营养保健品,对 Cyp 诱导的大鼠肝毒性具有肝保护作用。