An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures.
An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures.
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DOI：
10.1016/j.tox.2016.10.001
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发表时间：
2016-09-14
期刊：
影响因子：
4.5
通讯作者：
de Graaf IA
中科院分区：
文献类型：
--
作者：
Dugbartey GJ;Peppone LJ;de Graaf IA
顺铂是目前应用最广泛的治疗多种恶性肿瘤的化疗药物之一。然而，其临床应用受到固有的肾和心脏毒性和其他副作用的限制，其潜在机制仅被部分了解。实验研究表明，顺铂会产生活性氧物种，损害细胞的抗氧化防御系统，导致氧化应激和加重损伤，从而最终导致肾脏和心力衰竭。了解顺铂引起的肾和心脏毒性的分子机制可能有助于临床医生更好地预防或治疗这一问题，也可能为研究药物引起的器官毒性提供一个模型。本文讨论了顺铂引起的肾和心脏毒性的一些主要分子机制，包括破坏细胞的离子稳态和能量状态，导致细胞损伤和细胞死亡。我们强调了毒性的临床表现以及(新的)生物标记物，如肾损伤分子-1(Kim-1)、金属蛋白酶组织抑制因子-1(TIMP-1)和N-末端前-B型利钠肽(NT-proBNP)。我们还提出了一些目前的治疗挑战，并提出了可能减轻或预防这些毒性的新型药理化合物的潜在保护策略，其中包括使用硫化氢。
Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide.
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DOI：
10.1097/shk.0000000000000478
发表时间：
2016-01
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Ahmad A;Olah G;Szczesny B;Wood ME;Whiteman M;Szabo C
通讯作者：
Szabo C
影响因子：
13.6
作者：
Davis, CA;Nick, HS;Agarwal, A
通讯作者：
Agarwal, A
影响因子：
5.1
作者：
Ansari, Shakila Banu;Kurian, Gino A.
通讯作者：
Kurian, Gino A.
影响因子：
3.5
作者：
Dolci, Alberto;Dominici, Roberto;Panteghini, Mauro
通讯作者：
Panteghini, Mauro
影响因子：
5.3
作者：
Dzagnidze, Anna;Katsarava, Zaza;Thomale, Juergen
通讯作者：
Thomale, Juergen