Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats.
Effects of Exercise Preconditioning on Doxorubicin-Induced Liver and Kidney Toxicity in Male and Female Rats.
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DOI：
10.3390/ijms241210222
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发表时间：
2023-06-16
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
多柔比星（DOX）是用于癌症治疗的高效化疗剂。然而，由于在健康组织中的脱靶毒性，DOX的临床使用受到限制。在这方面，肝和肾代谢清除导致DOX在这些器官系统内积累。在肝脏和肾脏内，DOX引起炎症和氧化应激，从而促进细胞毒性细胞信号传导。虽然目前没有治疗DOX肝和肾毒性的标准护理，但耐力运动预处理可能是预防肝丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）升高并改善肾肌酐清除率的有效干预措施。为了确定运动预处理是否足以减少急性暴露于DOX化疗治疗引起的肝脏和肾脏毒性，雄性和雌性Sprague-Dawley大鼠在盐水或DOX暴露前保持久坐或进行运动训练。我们的研究结果表明，DOX治疗会升高雄性大鼠的AST和AST/ALT，而运动预处理对防止这些升高没有影响。我们还发现，血浆中的肾素-血管紧张素-醛固酮系统（RAAS）激活标志物和尿中的蛋白尿和近端小管损伤标志物增加，雄性大鼠与雌性大鼠相比差异更大。运动预处理显示男性尿肌酐清除率提高，胱抑素C降低，而女性血浆血管紧张素II（AngII）水平降低。我们的研究结果表明，组织和性别特异性反应与运动预处理和DOX治疗对肝脏和肾脏毒性标志物的影响有关。
Doxorubicin (DOX) is a highly effective chemotherapy agent prescribed for cancer treatment. However, the clinical use of DOX is limited due to off-target toxicity in healthy tissues. In this regard, hepatic and renal metabolic clearance results in DOX accumulation within these organ systems. Within the liver and kidneys, DOX causes inflammation and oxidative stress, which promotes cytotoxic cellular signaling. While there is currently no standard of care to treat DOX hepatic- and nephrotoxicity, endurance exercise preconditioning may be an effective intervention to prevent elevations in liver alanine transaminase (ALT) and aspartate aminotransferase (AST) and to improve kidney creatinine clearance. To determine whether exercise preconditioning is sufficient to reduce liver and kidney toxicity resulting from acute exposure to DOX chemotherapy treatment, male and female Sprague–Dawley rats remained sedentary or were exercise trained prior to saline or DOX exposure. Our findings demonstrate that DOX treatment elevated AST and AST/ALT in male rats, with no effects of exercise preconditioning to prevent these increases. We also showed increased plasma markers of renin–angiotensin–aldosterone system (RAAS) activation and urine markers of proteinuria and proximal tubule damage, with male rats revealing greater differences compared to females. Exercise preconditioning showed improved urine creatinine clearance and reduced cystatin c in males, while females had reduced plasma angiotensin II (AngII) levels. Our results demonstrate both tissue- and sex-specific responses related to the effects of exercise preconditioning and DOX treatment on markers of liver and kidney toxicity.
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DOI：
10.1016/j.jpba.2020.113576
发表时间：
2020-11-30
影响因子：
3.4
作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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