Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress.
Dose-dependent effects of cisplatin on the severity of testicular injury in Sprague Dawley rats: reactive oxygen species and endoplasmic reticulum stress.
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DOI：
10.2147/dddt.s120014
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Park JK
中科院分区：
文献类型：
--
作者：
Soni KK;Kim HK;Choi BR;Karna KK;You JH;Cha JS;Shin YS;Lee SW;Kim CY;Park JK
顺铂（CIS）用于治疗癌症，但其非特异性全身作用导致对身体其他部位的毒性作用。本研究通过在恒定时间段内增加剂量来研究CIS毒性的严重程度。将Sprague道利大鼠分为5个处理组和对照组，分别腹腔注射CIS（2、4、6、8和10 mg/kg）5天。测量大鼠体重、脏器重量、附睾精子计数、精子活率和精子凋亡率。对血液样本进行全血细胞计数、活性氧和氮物质、丙二醛水平和总睾酮评价。检测睾丸组织中类固醇生成急性调节蛋白和内质网应激蛋白。收集附睾精子用于CatSper Western blot。比较不同剂量CIS对睾丸和肾脏的毒性作用。CIS给药组的体重、睾丸、附睾、前列腺、精囊和肾脏重量、精子计数、精子活力、类固醇生成急性调节蛋白水平和附睾精子计数均显著低于对照组。相反，精子凋亡，血浆活性氧和氮，丙二醛，睾酮，红细胞，红细胞压积，血红蛋白和内质网应激蛋白水平均增加。虽然CIS有效地治疗癌症，但在增加剂量时，它对泌尿生殖系统和身体其他部位具有毒性和生命威胁。
Cisplatin (CIS) is used in the treatment of cancer, but its nonspecific systemic actions lead to toxic effects on other parts of the body. This study investigated the severity of CIS toxicity by increasing its dose over a constant time period. Sprague Dawley rats were divided into five treatment groups and control group with CIS (2, 4, 6, 8, and 10 mg/kg) administered intraperitoneally for 5 days. The body and organs were weighed, epididymal sperm was counted, and sperm motility and sperm apoptosis were evaluated. Blood samples were evaluated for complete blood count, reactive oxygen and nitrogen species, malondialdehyde levels, and total testosterone. The testicular tissue was examined for steroidogenic acute regulatory protein and endoplasmic reticulum stress protein. Epididymal sperm was collected for CatSper Western blot. The toxic effects of different doses of CIS on the testis and kidney were compared histologically. The weights of body, testis, epididymis, prostate, seminal vesicle, and kidney; sperm count; sperm motility; steroidogenic acute regulatory protein level; and epididymal sperm count were significantly lower in the CIS-treated groups than in the control group. In contrast, sperm apoptosis, plasma reactive oxygen and nitrogen species, and malondialdehyde, testosterone, red blood cell, hematocrit, hemoglobin, and endoplasmic reticulum stress protein levels all increased. Though CIS effectively treats cancer, at an increased dose it is toxic and life-threatening to the genitourinary system and other parts of the body.