Effects of dimethyl sulfoxide (DMSO) on pulmonary fibrosis in rats and mice.
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.
Haschek
W M
WM
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana 61801.
Baer
K E
KE
Rutherford
J E
JE
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D006909:Hydroxyproline / Q000032:analysis; D008168:Lung / Q000032:analysis / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D001761:Bleomycin; D002084:Butylated Hydroxytoluene; D006909:Hydroxyproline; D004121:Dimethyl Sulfoxide