Harchegani Asghar Beigi, Khor Abolfazl, Niha Mahdiyeh Mirnam, Kaboutaraki Hamid Bakhtiari, Shirvani Hossein, Shahriary Alireza
Chemical Injuries Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Medical Radiation Engineering, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Interdiscip Toxicol. 2019 Dec;12(4):186-191. doi: 10.2478/intox-2019-0023. Epub 2020 Apr 30.
Vincristine (VCR) is an important anti-cancer drug, which is highly toxic for the liver. This study aimed at evaluating the protective effect of alcoholic extract of saffron stigma against vincristine hepatotoxicity in the rat. A total number of 50 rats were randomly divided into 10 groups, including controls, rats receiving 0.25 mg/kg (A group), 0.5 mg/kg (B group), 0.75 mg/kg (C group) VCR, 0.25 mg/kg VCR + 0.5 mg/kg saffron (D group), 0.5 mg/kg VCR + 0.5 mg/kg saffron (E group), 0.75 mg/kg VCR + 0.5 mg/kg saffron (F group), 0.25 mg/kg VCR + 1mg/kg saffron (G group), 0.5 mg/kg VCR + 1 mg/kg saffron (H group), and 0.75 mg/kg VCR + 1 mg/kg saffron (I group) groups. Serum level of liver enzymes, including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and bilirubin were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using ferric reducing antioxidant of power (FRAP) and thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR, especially at the concentration of 0.75mg/kg, caused severe hepatic injury with significant increase in the levels of AST (582.0±39.45 UI), ALT (124.0±5.92 UI), ALP (939.8±89.8 UI) enzymes and bilirubin (0.17±0.008). VCR administration also significantly increased the serum MDA level (0.49±0.021 nmol/ml), while TAC value was declined significantly (241.27±18.27 μmol/l). These effects were dose-dependent. Treatment with saffron extract decreased the activity of liver enzymes and MDA values in hepatotoxic rats with a significant enhancement in serum TAC content. These effects were notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced hepatotoxicity, antioxidant depletion and lipid peroxidation, presumably due to its antioxidative properties.
长春新碱（VCR）是一种重要的抗癌药物，对肝脏具有高毒性。本研究旨在评估藏红花柱头乙醇提取物对大鼠长春新碱肝毒性的保护作用。总共50只大鼠被随机分为10组，包括对照组、接受0.25mg/kg（A组）、0.5mg/kg（B组）、0.75mg/kg（C组）长春新碱的大鼠、0.25mg/kg长春新碱+0.5mg/kg藏红花（D组）、0.5mg/kg长春新碱+0.5mg/kg藏红花（E组）、0.75mg/kg长春新碱+0.5mg/kg藏红花（F组）、0.25mg/kg长春新碱+1mg/kg藏红花（G组）、0.5mg/kg长春新碱+1mg/kg藏红花（H组）以及0.75mg/kg长春新碱+1mg/kg藏红花（I组）。在实验期结束时，使用特定试剂盒测量血清肝酶水平，包括天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）和胆红素。分别使用铁还原抗氧化能力（FRAP）和硫代巴比妥酸反应（TBAR）方法测量血清总抗氧化能力（TAC）和丙二醛（MDA）值。给予长春新碱，尤其是浓度为0.75mg/kg时，会导致严重的肝损伤，AST（582.0±39.45 UI）、ALT（124.0±5.92 UI）、ALP（939.8±89.8 UI）酶和胆红素（0.17±0.008）水平显著升高。给予长春新碱还会显著增加血清MDA水平（0.49±0.021 nmol/ml），而TAC值则显著下降（241.27±18.27 μmol/l）。这些作用呈剂量依赖性。用藏红花提取物治疗可降低肝毒性大鼠的肝酶活性和MDA值，并显著提高血清TAC含量。对于接受1mg/kg植物提取物的大鼠，这些作用尤为显著。给予藏红花，尤其是较高浓度时，可减轻长春新碱诱导的肝毒性、抗氧化剂耗竭和脂质过氧化，这可能归因于其抗氧化特性。
