Haschek W M, Baer K E, Rutherford J E
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana 61801.
Toxicology. 1989 Feb;54(2):197-205. doi: 10.1016/0300-483x(89)90045-0.
Dimethyl sulfoxide (DMSO), a putative anti-inflammatory agent and free radical scavenger, was shown to protect against acute bleomycin-induced pulmonary fibrosis in the rat (Pepin and Langner, Biochem. Pharmacol., 34 (1985) 2386). We examined the effect of DMSO on bleomycin-induced pulmonary toxicity in Swiss outbred mice and Sprague-Dawley rats, and on butylated hydroxytoluene (BHT)-induced pulmonary toxicity in Swiss outbred mice. Bleomycin (BL)-induced mortality in mice (20% at 0.1 units BL) and rats (50% at 1.5 units BL) was increased to 100% by daily DMSO (5 g/kg 50% in saline). Similar DMSO treatment after lower doses of bleomycin (1 unit BL in rats and 0.075 or 0.050 units in mice) increased lung hydroxyproline content in the rat but had no effect in the mouse. Lung hydroxyproline content in mice 14 days after 400 mg/kg BHT in corn oil was also slightly increased by daily DMSO at 5 g/kg, but not at 1 or 2 g/kg. Daily DMSO (5 g/kg) did not alter cellular proliferation [( 14C]thymidine incorporation into pulmonary DNA) in the lung at 2 or 5 days after BHT. Thus, we found that DMSO potentiated the lethality of bleomycin, and potentiated or had no effect on bleomycin or BHT-induced pulmonary fibrosis in the rat and mouse.
二甲基亚砜（DMSO）是一种公认的抗炎剂和自由基清除剂，已证明其可保护大鼠免受博来霉素诱导的急性肺纤维化（Pepin和Langner，《生物化学与药理学》，34（1985）2386）。我们研究了DMSO对瑞士远交系小鼠和Sprague-Dawley大鼠博来霉素诱导的肺毒性，以及对瑞士远交系小鼠丁基羟基甲苯（BHT）诱导的肺毒性的影响。每天给予DMSO（5 g/kg，50%溶于生理盐水）可使博来霉素（BL）诱导的小鼠（0.1单位BL时为20%）和大鼠（1.5单位BL时为50%）死亡率增至100%。在较低剂量的博来霉素（大鼠1单位BL，小鼠0.075或0.050单位）后进行类似的DMSO处理，可使大鼠肺羟脯氨酸含量增加，但对小鼠无影响。玉米油中400 mg/kg BHT处理14天后，每天给予5 g/kg的DMSO可使小鼠肺羟脯氨酸含量略有增加，但1或2 g/kg时无此作用。每天给予DMSO（5 g/kg）在BHT处理后2或5天时不会改变肺细胞增殖[（14C）胸苷掺入肺DNA]。因此，我们发现DMSO增强了博来霉素的致死性，并且对大鼠和小鼠博来霉素或BHT诱导的肺纤维化有增强作用或无影响。
