Fresh Garlic Extract Protects The Liver Against Acetaminophen-Induced Toxicity

Christian Chinyere Ezeala; Ifeoma Nneka Nweke; Prince C. Unekwe; Ibrahim Ahmed El-Safty; Emenike Jacob Nwaegerue

摘要

Acetaminophen toxicity is a major course of acute liver failure. Many plants have been reported to show hepatoprotective activities. This study was to determine the protective potential of fresh garlic extract on acetaminophen toxicity and to demonstrate its dose dependence. Sixty Swiss mice were divided into six groups of ten. Group I served as negative control and were treated with physiological saline. Group II served as the positive control and received 250 mg/kg body weight of acetaminophen only. Groups III, IV, and V were pretreated with daily administration of 250 mg/kg, 500 mg/kg, and 750 mg/kg of garlic respectively, for five days followed by 250 mg/kg of acetaminophen. Group VI were pretreated with 25 mg/kg silymarin prior to 250 mg/kg acetaminophen. Blood samples were collected after six hours of acetaminophen and used for biochemical studies, while liver was excised from each mouse and used to prepare hematoxylin / eosin sections. The alterations in AST, ALT, alkaline phosphatase, and serum albumin were significantly prevented by prior administration of garlic extract. Also the histological changes induced by acetaminophen overdose were prevented by garlic. We conclude that fresh garlic extract protected the liver against toxic doses of acetaminophen and suggest that its use could protect against hepatitis. Introduction Hepatitis is a major public health problem in the world today and acetaminophen overdose contributes significantly to cases of drug induced hepatitis. 12 Acetaminophen is quite safe and well tolerated in therapeutic doses. However, at toxic doses, acetaminophen produces acute liver failure characterized by centrilobular necrosis in both man and experimental animals. 3 This has been attributed to the metabolic activation of acetaminophen to a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI) in the liver by cytochrome p450 isoenzymes especially CYP2E1. 4 NAPQI reportedly depletes liver glutathione thereby inducing oxidative stress. It also binds to vital cellular and mitochondrial proteins leading to cellular necrosis, and it could activate cells of the immune system leading to the release of pro-inflammatory cytokines. 56 Many natural products have been reported to possess antioxidant and hepatoprotective effects in animal models of hepatotoxicity and quite a good number are employed in folk medicine for the treatment of liver diseases. Currently, many plant extracts have been studied, and some have received approval or are undergoing clinical trial for use in liver related conditions. 78910 Garlic is widely consumed in many cultures as spice and as condiment in many dishes. Several cultures use garlic for medicinal purposes. A plethora of publications are also available on the pharmacological properties of garlic and their beneficial health effects. 1112131415 Although many studies have focused on the antioxidant and anti-lipid peroxidative properties of garlic extracts, many of these studies employed aged garlic extract (AGE) that is known to have a different phytochemical composition from fresh garlic, and just a few reports investigated the actions of garlic oil. 1617 To our knowledge, no study has investigated the effect of fresh extract of local Ugandan cultivars of garlic on acetaminophen hepatotoxicity. In other to provide crucial information that is needed for the possible development of a prophylactic strategy for drug induced hepatitis, this study was designed to determine the usefulness of ethanolic extract of fresh garlic bulbs in preventing acetaminophen induced hepatotoxicity in mice. Specifically, we investigated its usefulness in preventing acetaminophen induced changes in serum biochemistry and liver histology, and dose dependence of these effects. Materials And Methods Plant Collection, Identification, and ExtractionLocal cultivars of garlic (Allium sativum L.) were purchased from a local market in Ishaka Town in Western Uganda, and identified by a qualified taxonomist, Prof

机译：对乙酰氨基酚毒性是急性肝衰竭的主要病程。据报道许多植物显示出肝保护活性。这项研究旨在确定新鲜大蒜提取物对乙酰氨基酚毒性的保护潜力，并证明其剂量依赖性。 60只瑞士小鼠被分成六组，每组十只。第一组作为阴性对照，并用生理盐水治疗。第二组作为阳性对照，仅接受250 mg / kg体重的对乙酰氨基酚。分别每天分别给250 mg / kg，500 mg / kg和750 mg / kg大蒜预处理III，IV和V组，持续5天，然后再对乙酰氨基酚250 mg / kg。第六组先用25 mg / kg水飞蓟素预处理，然后再使用250 mg / kg对乙酰氨基酚。对乙酰氨基酚六个小时后收集血样，用于生化研究，同时从每只小鼠中切出肝脏，用于制备苏木/曙红切片。事先服用大蒜提取物可明显预防AST，ALT，碱性磷酸酶和血清白蛋白的改变。大蒜还可以防止对乙酰氨基酚过量引起的组织学改变。我们得出的结论是，新鲜大蒜提取物可以保护肝脏免受毒性剂量的对乙酰氨基酚的侵害，并建议其使用可以预防肝炎。引言肝炎是当今世界上主要的公共卫生问题，对乙酰氨基酚的过量使用是导致药物性肝炎的重要原因。 12对乙酰氨基酚非常安全，在治疗剂量下耐受性良好。但是，在有毒剂量下，对乙酰氨基酚会在人和实验动物中产生急性肝衰竭，其特征是小叶中心坏死。 3这归因于对乙酰氨基酚通过肝脏中的细胞色素p450同工酶特别是CYP2E1代谢为有毒代谢产物N-乙酰基-对-苯醌亚胺（NAPQI）。据报道4 NAPQI耗尽了肝脏的谷胱甘肽，从而诱导了氧化应激。它也与重要的细胞和线粒体蛋白结合，导致细胞坏死，并且可以激活免疫系统细胞，导致促炎性细胞因子释放。 56据报道，许多天然产物在肝毒性动物模型中均具有抗氧化和保肝作用，并且在民间医学中有相当多的天然产物用于治疗肝病。目前，已经研究了许多植物提取物，其中一些已经被批准或正在临床试验中用于肝脏相关疾病。 78910在许多文化中，大蒜被广泛用作香料和调味品。几种文化都将大蒜用于药用。关于大蒜的药理特性及其有益健康的作用，也有大量出版物。 1112131415尽管许多研究都集中在大蒜提取物的抗氧化和抗脂质过氧化特性上，但其中许多研究都使用了老化的大蒜提取物（AGE），该提取物的成分与新鲜大蒜的化学成分不同，仅有少数报告对这种提取物进行了研究。大蒜油的作用。 1617据我们所知，尚无研究调查乌干达当地大蒜的新鲜提取物对乙酰氨基酚肝毒性的作用。为了提供可能的药物预防性肝炎预防策略发展所需的重要信息，本研究旨在确定新鲜大蒜鳞茎乙醇提取物在预防对乙酰氨基酚引起的小鼠肝毒性中的作用。具体而言，我们调查了其在预防对乙酰氨基酚引起的血清生化和肝脏组织学变化以及这些作用的剂量依赖性方面的有用性。材料和方法植物的收集，鉴定和提取当地的大蒜品种（Allium sativum L.）从乌干达西部Ishaka镇的当地市场购买，并由合格的分类学家，教授进行鉴定。

Fresh Garlic Extract Protects The Liver Against Acetaminophen-Induced Toxicity

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