洛伐他汀对多柔比星诱导的Balb-C小鼠心脏毒性的保护作用。

Abeera Sikandar, Khalida Ajmal, Ayesha Afzal, Saima Rafique, Ayman Zafar, Tahira Tehseen
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引用次数: 0

摘要

背景:阿霉素是治疗大量血液病和实体恶性肿瘤最常用的抗癌药物之一。然而,其剂量和持续时间受到与剂量相关的器官损害,特别是心脏毒性的限制。洛伐他汀是治疗高胆固醇血症的常用处方药,具有显著的抗氧化潜力。我们的研究旨在评估和比较两种预处理方案对阿霉素引起的心脏损伤的心脏保护作用。方法:采用实验室随机对照实验,选取BALB/c小鼠40只,随机分为5组(n=8)。1组为对照组,2组腹腔注射阿霉素10mg/kg。3组口服洛伐他汀10mg/kg,连续5天。第4组和第5组分别连续给予洛伐他汀5天和第10天,第3天和第8天给予阿霉素。结果:阿霉素引起心肌酶明显升高;肌酸激酶MB (CK-MB)和乳酸脱氢酶(LDH) (p值≤0.0001),心脏组织学改变为中度。在10天的研究设计中,洛伐他汀显著减轻了LDH和CK-MB的损伤,p值≤0.001,而在5天的设计中,观察到LDH和CK-MB的恢复效率略低,p值≤0.001和0.012。两种预处理方案的组织学保存均符合生物标志物。结论:在以阿霉素为基础的治疗方案中,使用一种容易获得且安全的他汀类药物预处理至少7天,可有效预防其潜在的危及生命的心脏毒性。
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Evaluating The Protective Effects Of Lovastatin Against Doxorubicin Induced Cardiotoxicity In Balb-C Mice.

Background: Doxorubicin is one of the most commonly used anti-cancer drugs that treat a large number of haematological and solid malignancies. Its usage in dose and duration is nevertheless restricted by dose related organ damage, particularly cardiotoxicity. Lovastatin is a commonly prescribed drug for hypercholesterolemia and possesses remarkable antioxidant potential. Our study was aimed at evaluating and comparing its cardioprotective effect in two pre-treatment schedules against doxorubicin-induced cardiac damage.

Methods: In this lab-based randomized controlled experiment, 40 BALB/c mice were randomly grouped into five groups (n=8). Group 1 served as control whereas Group 2 was given doxorubicin intraperitoneally at a dose of 10mg/kg. Group 3 received 10mg/kg of oral lovastatin for five days. Groups 4 and 5 were administered lovastatin for five and ten consecutive days correspondingly and doxorubicin was given on 3rd and 8th experimental days of these groups.

Results: Doxorubicin caused a significant rise in cardiac enzymes; Creatine kinase MB (CK-MB) and Lactate Dehydrogenase (LDH) (p value ≤0.0001) whereas cardiac histological alterations were ranked as moderate. The damage was significantly attenuated by lovastatin in the ten-day study design with a p-value of ≤0.001 for both LDH and CK-MB whereas a slightly less efficient restoration was observed in the five-day design with a p value of ≤0.001 for LDH and 0.012 for CK-MB. Histological preservation in both pre-treatment schedules was in accordance with the biological markers.

Conclusions: In doxorubicin-based regimens, pretreatment for at least seven days with an easily available and safe statin can effectively prevent its potentially life threatening cardiotoxicity.

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