School of Biosciences and Technology, Vellore Institute of Technology, Tamil Nadu, Vellore, 632014, India.
Appl Biochem Biotechnol. 2023 Oct;195(10):6256-6275. doi: 10.1007/s12010-023-04392-2. Epub 2023 Feb 28.
Paracetamol is the most predominantly used antipyretic and analgesic drug. As paracetamol is metabolised mostly in the liver, both deliberate and unintentional overdoses of paracetamol are reported to provoke severe hepatotoxicity, including liver failure. Caesalpinia bonducella seed is well known for its medicinal and therapeutic properties. However, there is no report on its potential protective effects against paracetamol-instigated hepatotoxicity. Therefore, we studied the protective effects of aqueous seed extract of Caesalpinia bonducella (ASECB) on paracetamol-instigated hepatotoxicity in rats. Thirty female albino rats were divided into five groups: control, paracetamol-intoxicated, ASECB + paracetamol, silymarin + paracetamol, and ASECB alone. The rats were assessed for liver enzyme markers (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase), antioxidant activity (superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase), lipid peroxidation (malondialdehyde), histopathological, cytokine levels (pro-inflammatory cytokines TNF-α and IL-6, and anti-inflammatory cytokine IL-10), and protein expression (pro-apoptotic markers caspase 3 and caspase 8 and anti-apoptotic marker Bcl-2) after the 8-day study period. Repercussions of paracetamol intoxication induced upregulation of liver enzyme markers, antioxidant depletion, malondialdehyde production, decreased expression of Bcl-2 and IL-10, and overexpression of apoptotic and pro-inflammatory mediators, which were attenuated by pre-treatment with ASECB. ASECB markedly mitigated paracetamol-instigated liver injury by suppressing caspase-8/3 signalling and inflammatory infiltration in liver tissue by significantly reducing TNF-α and IL-6. In conclusion, ASECB pre-treatment exerts potent liver protection against paracetamol-instigated hepatotoxicity evidenced by mitigation of oxidative stress, lipid peroxidation, inflammation, and apoptosis.
对乙酰氨基酚是最主要的解热镇痛药。由于对乙酰氨基酚主要在肝脏代谢，无论是故意还是无意过量使用对乙酰氨基酚都会引起严重的肝毒性，包括肝衰竭。波罗蜜种子以其药用和治疗特性而闻名。然而，目前尚无关于其对乙酰氨基酚诱导的肝毒性的潜在保护作用的报道。因此，我们研究了波罗蜜种子水提物（ASECB）对乙酰氨基酚诱导的大鼠肝毒性的保护作用。将 30 只雌性白化大鼠分为五组：对照组、对乙酰氨基酚中毒组、ASECB+对乙酰氨基酚组、水飞蓟素+对乙酰氨基酚组和 ASECB 单独组。在 8 天的研究期间，评估了大鼠的肝脏酶标志物（碱性磷酸酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-谷氨酰转肽酶）、抗氧化活性（超氧化物歧化酶、过氧化氢酶、还原型谷胱甘肽、谷胱甘肽过氧化物酶）、脂质过氧化（丙二醛）、组织病理学、细胞因子水平（促炎细胞因子 TNF-α和 IL-6，以及抗炎细胞因子 IL-10）和蛋白表达（促凋亡标志物 caspase 3 和 caspase 8 和抗凋亡标志物 Bcl-2）。对乙酰氨基酚中毒引起的肝酶标志物上调、抗氧化剂耗竭、丙二醛产生、Bcl-2 和 IL-10 表达减少以及凋亡和促炎介质过度表达，经 ASECB 预处理后得到缓解。ASECB 通过抑制 caspase-8/3 信号通路和显著减少 TNF-α和 IL-6 来减轻肝组织中的炎症浸润，从而显著减轻对乙酰氨基酚引起的肝损伤。总之，ASECB 预处理通过减轻氧化应激、脂质过氧化、炎症和凋亡，对乙酰氨基酚引起的肝毒性具有显著的肝脏保护作用。
