Hepatoprotective Potential of Micronutrients Against Methotrexate-Induced Hepatotoxicity in Experimental Mice Model

Aamna Khokhar, Momina Khokhar, Zunera Hakim, Sarah Saleem
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Abstract

Objective: To evaluate the hepatoprotective role of micronutrients, ascorbic acid and alpha-tocopherol, against methotrexate (MTX)-induced hepatic damage in mice. Methodology: A laboratory-based experimental study was carried out at Foundation University Medical College in collaboration with the National Institute of Health, Islamabad, from October to December 2021. Twenty-four male BALB/c mice were randomly divided into four groups (n=6). Group I received intraperitoneal normal saline. Group II received a single intraperitoneal injection of MTX at a dose of 20 mg/kg. Groups III and IV were given oral ascorbic acid (200 mg/kg) and oral alpha-tocopherol (100 mg/kg) respectively, both for 7 days, with MTX administered on day 4. Blood and liver samples were collected 24 hours after the last dose for evaluation of hepatic serum biomarkers and histological analysis, respectively. Results: Ascorbic acid demonstrated a protective effect against MTX-induced hepatic damage. However, alpha-tocopherol did not show hepatoprotection on liver histopathology. Conclusion: Ascorbic acid exhibits protective potential when administered concomitantly with MTX. However, alpha-tocopherol does not provide complete hepatoprotection against MTX-induced liver injury.
微量营养素对甲氨蝶呤诱导的实验小鼠肝毒性的保护潜力
目的评估抗坏血酸和α-生育酚这两种微量营养素对甲氨蝶呤(MTX)诱导的小鼠肝损伤的保护作用:2021 年 10 月至 12 月,基础大学医学院与伊斯兰堡国家健康研究所合作开展了一项实验室实验研究。24 只雄性 BALB/c 小鼠被随机分为四组(n=6)。I 组腹腔注射生理盐水。第二组腹腔注射一次剂量为 20 毫克/千克的 MTX。第三组和第四组分别口服抗坏血酸(200 毫克/千克)和α-生育酚(100 毫克/千克),疗程均为 7 天,第 4 天服用 MTX。最后一次给药 24 小时后采集血液和肝脏样本,分别用于评估肝血清生物标志物和组织学分析:结果:抗坏血酸对MTX诱导的肝损伤有保护作用。结果:抗坏血酸对 MTX 引起的肝损伤有保护作用,但α-生育酚对肝组织病理学没有保护作用:结论:抗坏血酸与MTX同时服用具有保护作用。结论:抗坏血酸与 MTX 同时服用时具有保护作用,但α-生育酚并不能对 MTX 引起的肝损伤提供完全的肝保护作用。
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