Binu Prakash, Priya Nellikunnath, Abhilash Surendran, Vineetha Radhakrishnan Chandraprabha, Nair Harikumaran
School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India.
Iran J Med Sci. 2018 May;43(3):305-312.
Arsenic trioxide (As2O3) has shown effectiveness in the treatment of leukemia, but it is also associated with hepatotoxicity. Given antileukemic drug-induced oxidative stress and toxicity, this study focused on the mitigatory role of eugenol, a monoterpene compound from clove oil, in the hepatic tissue of Wistar rats.
Twenty-four male Wistar rats (180-250 g) were randomly divided into 4 groups (6 rats per group): normal control rats, rats treated with AsO (4 mg/kg bwt), rats treated with eugenol (5 mg/kg bwt), and rats receiving co-treatment with AsO (4 mg/kg bwt) and eugenol (5 mg/kg bwt), all of which orally administered for a period of 30 days. The Tukey test (Origin version 7, Origin Lab Corporation, Northampton, USA) was applied to analyze the one-way analysis of variance (ANOVA) between the different groups. A P value less than 0.05 was considered significant.
Oral administration of As2O3 significantly induced hepatic damage, evident from increased levels of aspartate transaminase and alanine transaminase (P=0.01 and P<0.001, respectively). Moreover, a decrease in the activities of enzymatic and nonenzymatic antioxidants altered electrolyte concentration and increased the rate of lipid peroxidation (P=0.04) and the level of nitric oxide (P=0.01). Accumulation studies and histopathological analyses confirmed the biochemical variations. Co-treatment with eugenol (5 mg/kg bwt) exhibited hepatoprotective effects as manifested by the decreased rate of arsenic accumulation, lipid peroxidation, and nitric oxide level along with normalized levels of antioxidants and maintained histology of the liver.
Eugenol may be used in combination with arsenic trioxide in chemotherapy to reduce oxidative damage to the hepatic system.
三氧化二砷(As₂O₃)已显示出对白血病的治疗效果,但它也与肝毒性有关。鉴于抗白血病药物会引起氧化应激和毒性,本研究聚焦于丁香酚(一种来自丁香油的单萜化合物)对Wistar大鼠肝组织的减轻作用。
将24只雄性Wistar大鼠(体重180 - 250克)随机分为4组(每组6只):正常对照大鼠、用AsO(4毫克/千克体重)处理的大鼠、用丁香酚(5毫克/千克体重)处理的大鼠以及接受AsO(4毫克/千克体重)和丁香酚(5毫克/千克体重)联合处理的大鼠,所有处理均通过口服给药,持续30天。应用Tukey检验(Origin 7版本,美国北安普顿的Origin Lab公司)分析不同组之间的单因素方差分析(ANOVA)。P值小于0.05被认为具有显著性。
口服As₂O₃显著诱导肝损伤,这从天门冬氨酸转氨酶和丙氨酸转氨酶水平升高可以明显看出(分别为P = 0.01和P < 0.001)。此外,酶促和非酶促抗氧化剂活性降低,电解质浓度改变,脂质过氧化速率增加(P = 0.04)以及一氧化氮水平升高(P = 0.01)。蓄积研究和组织病理学分析证实了这些生化变化。与丁香酚(5毫克/千克体重)联合处理表现出肝脏保护作用,表现为砷蓄积率、脂质过氧化和一氧化氮水平降低,同时抗氧化剂水平恢复正常以及肝脏组织学保持正常。
丁香酚可与三氧化二砷联合用于化疗,以减少对肝脏系统的氧化损伤。