Ilukho Fidelis Azagbor, Fasipe Olumuyiwa John, Aigbe Flora Ruth
Department of Pharmacology & Therapeutics, Faculty of Basic Clinical Sciences, College of Medicine, Edo University, Iyamho, Edo state, Nigeria.
Department of Pharmacology & Therapeutics, Faculty of Basic Clinical Sciences, College of Medicine, University of Medical Sciences, Ondo City, Ondo State, Nigeria.
Future Sci OA. 2022 Jun 17;8(6):FSO801. doi: 10.2144/fsoa-2021-0119. eCollection 2022 Jul.
Drug-induced hepatotoxicity is a major public health issue of concern. It significantly affects the development of new pharmaceutical drugs and has led to the withdrawal of many promising pharmaceutical drugs from the pharmaceutical market.
The aim of this study was to evaluate the hepatoprotective, ameliorative and antioxidant effects of the crude aqueous leafy extract of plant and its different separating medium fractions against acute acetaminophen (paracetamol)-induced hepatotoxicity in a mouse model.
METHODS & MATERIALS: Twelve different groups of six mice (three males and three females) were used for this study. Acetaminophen at a single lethal hepatotoxic dose of 3 g/kg was orally administered on the seventh day to the mice in groups 2 to 12 after their 6-day pretreatment duration for the induction of hepatotoxicity; and were then left for 24 hours before the collection of specimen samples were completed, while group 1 served as control.
The crude aqueous leafy extract of (125-250 mg/kg) produced a dose-dependent reversal of the lethal hepatotoxic effect of oral 3 g/kg dose of paracetamol. At the dose of 250 mg/kg, it significantly (p < 0.0001) reduced the levels of hepatic enzymes markers (alanine transaminase [ALT], aspartate transaminase [AST] and alkaline phosphatase [ALP]) in the serum of treated animals. Also, the effects of the crude aqueous leafy extract were found to be statistically significant (p < 0.0001) more than that of its different separating medium fractional components.
The findings from this study demonstrated that the crude aqueous leafy extract of possesses hepatoprotective effect, possibly mediated through the induction of antioxidant enzymes to prevent the occurrence of oxidative stress damage or most likely through the inhibition of pro-inflammatory mediators which are being induced by the lethal hepatotoxic dose of paracetamol.
药物性肝毒性是一个备受关注的重大公共卫生问题。它显著影响新型药物的研发,并导致许多有前景的药物从药品市场撤出。
本研究旨在评估植物叶水粗提物及其不同分离介质组分对小鼠模型中急性对乙酰氨基酚(扑热息痛)诱导的肝毒性的保肝、改善和抗氧化作用。
本研究使用了12个不同组,每组6只小鼠(3只雄性和3只雌性)。在第6天预处理期后,于第7天对第2至12组的小鼠口服给予单一致死肝毒性剂量3 g/kg的对乙酰氨基酚以诱导肝毒性;然后在完成标本采集前留置24小时,而第1组作为对照。
植物叶水粗提物(125 - 250 mg/kg)产生了剂量依赖性的对口服3 g/kg剂量扑热息痛致死肝毒性作用的逆转。在250 mg/kg剂量下,它显著(p < 0.0001)降低了治疗动物血清中肝酶标志物(丙氨酸转氨酶[ALT]、天冬氨酸转氨酶[AST]和碱性磷酸酶[ALP])的水平。此外,发现叶水粗提物的作用在统计学上比其不同分离介质组分的作用更显著(p < 0.0001)。
本研究结果表明,植物叶水粗提物具有保肝作用,可能是通过诱导抗氧化酶来预防氧化应激损伤的发生,或者最有可能是通过抑制由致死剂量扑热息痛诱导的促炎介质来实现的。