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首页> 外文期刊>The Journal of toxicological sciences >Effects of erlotinib on lung injury induced by intratracheal administration of bleomycin (BLM) in rats
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Effects of erlotinib on lung injury induced by intratracheal administration of bleomycin (BLM) in rats

机译：厄洛替尼对气管内施用博莱霉素（BLM）所致大鼠肺损伤的影响

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摘要

Interstitial lung disease has been reported in cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors, erlotinib and gefitinib. Preclinical safety studies with erlotinib did not show any evidence for an induction of injury on intact lungs in rats and dogs. In the present study, we investigated the effects of erlotinib on lung injury induced by intratracheal administration of bleomycin (BLM) in rats. In Experiment 1, we examined the effects of short-term (7- and 21-day) administration of erlotinib (10 mg/kg/day, p.o.; subtoxic dose) on the BLM (0.1 or 0.6 mg/rat)-induced lung injury of slight and moderate severity. In Experiment 2, we examined the effects of long term (up to 63-day) administration of higher-dose (up to 20 mg/kg/day; toxic dose; accompanied with decreased body weight gain and severe skin lesions) erlotinib on the BLM-induced lung injury. In rats receiving erlotinib alone, no lung lesions were noted. In rats receiving BLM alone, diffuse alveolar damage (DAD) and, subsequently, pulmonary flbrosis of slight or moderate severity was observed. The administration of erlotinib to BLM-treated rats showed no exacerbation of lung injuries in indices such as macroscopic findings, lung weights, histopathological scores (lung lesion density and lung flbrosis score), and pulmonary hydroxyproline (HyP) level. These results suggest that erlotinib does not have any exacerbating effects on lung injuries induced by BLM in rats.
机译：在表皮生长因子受体酪氨酸激酶抑制剂，厄洛替尼和吉非替尼治疗的癌症患者中，已经报道了间质性肺疾病。厄洛替尼的临床前安全性研究未显示任何证据可诱导大鼠和狗的完整肺部受伤。在本研究中，我们调查了厄洛替尼对气管内注射博来霉素（BLM）诱导的大鼠肺损伤的影响。在实验1中，我们检查了短期（7天和21天）厄洛替尼（10毫克/千克/天，口服;亚毒性剂量）给药对BLM（0.1或0.6毫克/大鼠）诱导的肺的影响轻度和中度严重伤害。在实验2中，我们研究了长期（最多63天）长期服用高剂量（最高20 mg / kg /天;有毒剂量;伴随体重增加减少和严重的皮肤损伤）对厄洛替尼的影响BLM引起的肺损伤。在单独接受厄洛替尼的大鼠中，未发现肺部病变。在单独接受BLM的大鼠中，观察到弥漫性肺泡损伤（DAD），随后观察到轻度或中度严重程度的肺纤维化。厄洛替尼对BLM治疗的大鼠的给药在诸如宏观表现，肺重量，组织病理学评分（肺病变密度和肺纤维化评分）和肺羟脯氨酸（HyP）水平等指标上均未显示肺损伤加重。这些结果表明，厄洛替尼对BLM诱导的大鼠肺损伤没有任何加重作用。

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