PROTECTIVE EFFECT OF ICRF-187 ON DOXORUBICIN-INDUCED CARDIAC AND RENAL TOXICITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND NORMOTENSIVE (WKY) RATS
PROTECTIVE EFFECT OF ICRF-187 ON DOXORUBICIN-INDUCED CARDIAC AND RENAL TOXICITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND NORMOTENSIVE (WKY) RATS
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DOI：
10.1016/0041-008x(88)90226-8
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发表时间：
1988-01-01
影响因子：
3.8
通讯作者：
FERRANS, VJ
中科院分区：
文献类型：
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作者：
HERMAN, EH;ELHAGE, A;FERRANS, VJ
当雄性自发性高血压大鼠（SHR）和遗传相关的Wistar-Kyoto（WKY）大鼠每周一次静脉注射1 mg/kg阿霉素，持续12周时，发现体重减轻、心肌病和肾病是主要的毒性表现。这些变化中的每一个在SHR中更严重。从给药第7周至第12周观察到对体重的最显著影响。在此期间，SHR的体重下降到注射前的对照水平。在给予阿霉素的WKY中也发生了体重减轻，但没有那么严重。用25 mg/kg ICRF-187 ip预处理减弱了两种类型动物中多柔比星诱导的体重减轻。心脏和肾脏病变的频率和严重程度按0 - 4分进行分级。在所有SHR和五个单独给予阿霉素的WKY中的四个中发现了心脏的改变。细胞质空泡化和肌原纤维丢失在SHR（平均评分，2.6）比WKY（平均评分，1.0）更严重。在研究结束时，仅接受阿霉素的SHR的平均动脉压也降低。用ICRF-187预处理显著减轻了SHR（平均评分，1.0）和WKY（平均评分，0）中病变的严重程度;用ICRF-187和阿霉素处理的SHR的平均动脉压高于盐水处理的SHR。两种品系的大鼠均出现肾脏改变，包括肾小球空泡化和肾小管扩张（平均评分，SHR为4.0，WKY为3.0）。ICRF-187还降低了肾脏病变的严重程度（平均评分，SHR为2.0，WKY为1.0）。因此，虽然ICRF-187显着改变心肌，肾脏和体重的影响阿霉素在两个品系的大鼠，这些毒性作用是更严重的SHR比WKY。SHR提供了一个有用的动物模型，对阿霉素诱导的毒性具有潜在的保护活性的药物的关键检查。
Loss of body weight, cardiomyopathy, and nephropathy were the main toxic manifestations found when male spontaneously hypertensive rats (SHR) and genetically related Wistar-Kyoto (WKY) rats were given 1 mg/kg doxorubicin iv once a week for 12 weeks. Each of these alterations was more severe in SHR. The most profound effects on body weight were observed from the 7th to the 12th week of dosing. During this period the body weight of SHR declined to preinjection control levels. Weight loss also occurred in WKY given doxorubicin, but was not as profound. Pretreatment with 25 mg/kg ICRF-187 ip attenuated the doxorubicin-induced loss in body weight in both types of animals. The frequency and severity of cardiac and renal lesions were graded on a score of 0 to 4. Alterations were found in hearts of all SHR and four of five WKY given doxorubicin alone. Cytoplasmic vacuolization and myofibrillar loss were more severe in SHR (average score, 2.6) than in WKY (average score, 1.0). At the end of the study mean arterial pressure was also decreased in SHR which had received doxorubicin alone. Pretreatment with ICRF-187 significantly attenuated the severity of the lesions in both SHR (average score, 1.0) and WKY (average score, 0); mean arterial pressure was higher in SHR treated with ICRF-187 and doxorubicin than in saline-treated SHR. Renal alterations, including glomerular vacuolization and tubular dilatation, were found in both strains of rats (average scores, 4.0 in SHR and 3.0 in WKY). ICRF-187 also reduced the severity of renal lesions (average scores, 2.0 in SHR and 1.0 in WKY). Thus, although ICRF-187 significantly alters myocardial, renal, and body weight effects of doxorubicin in both strains of rats, these toxic effects are more severe in SHR than in WKY. SHR provide an useful animal model for the critical examination of agents with potential protective activity against doxorubicin-induced toxicity.