Abstract
Background: Accidental extravasation of doxorubicin leads to skin necrosis and significant morbidity. Based on our previous work in the rat, we hypothesized that the free radical scavengers dimethyl sulfoxide (DMSO) and vitamin C prevent doxorubicin-induced skin ulcers in white swine.
Methods: Fifteen white swine were anesthetized and injected with 0.5 mg of doxorubicin (1 mg/ml) intradermally delivered in saline, 10% DMSO, 20% DMSO, vitamin C (1 mg/ml), or vitamin C in 20% DMSO. Presence of skin ulceration and ulcer size, in the two greatest dimensions, was determined weekly for 3 weeks.
Results: Delivery of doxorubicin in DMSO and/or vitamin C lowered the ulcer incidence from 87% to 27% (p<0.0001) when compared with delivery in saline.
Conclusion: We conclude that the free radical scavengers DMSO and vitamin C are capable of lowering the incidence of doxorubicin-induced skin ulcers and could significantly lessen the morbidity associated with doxorubicin extravasation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Rudolph R, Larson DL. Etiology and treatment of chemotherapeutic agent extravasation injuries: a review.J Clin Oncol 1987;5(7):1116–26.
Larson DL. Treatment of tissue extravasation by antitumor agents.Cancer 1982;49:1796–9.
Coleman JJ, Walker AP, Didolkar MS. Treatment of adriamycin-induced skin ulcers: a prospective controlled study.J Surg Oncol 1983;22:129–35.
Desai MH, Teres D. Prevention of doxorubicin-induced skin ulcers in the rat and pig with dimethyl sulfoxide.Cancer Treat Rev 1982;66(6):1371–8.
Svingan BA, Powis G, Appel PL, et al. Protection against adriamycin-induced skin necrosis in the rat by dimethyl sulfoxide and L tocopherol.Cancer Res 1982;41:3395–9.
Dorr RT, Alberts DS, Cheer HSL. The limited role of corticosteroids in ameliorating experimental doxorubicin skin toxicity in the mouse.Cancer Chemother Pharmacol 1980;5:17–20.
Lebredo L, Barrie R, Woltering EA. DMSO protects against adriamycin-induced tissue necrosis.J Surg Res 1992;53:62–65.
Averbuch J, Boblt M, Gaudiamo G, et al. Experimental chemotherapy-induced skin necrosis in swine.J Clin Invest 1988;81:142–8.
Montagna W, Yun JS. The skin of the domestic pig.J Invest Dermatol 1964;43:11–21.
Bartek MJ, LaBudde JA, Maibach HI. Skin permeability in vivo: comparison in rat, rabbit, pig and man.J Invest Dermatol 1972;58:114–23.
Leudke DW. Histiopathogenesis of skin and subcutaneous injury induced by adriamycin.Plast Reconstr Surg 1979;63:463–5.
Bachur NR, Gee MV, Friedman RD. Nuclear catalyzed antibiotic free radical formation.Cancer Res 1982;42:1078–81.
Lown JW, Cheer HH, Plambeck JA, et al. Further studies on reactive oxygen species from activated anthracyclines and the relationship to cytotoxic action and cardiotoxic effects.Biochem Pharmacol 1982;31:575–81.
Friend C, Freedman HA. Effects and possible mechanisms of action of dimethyl sulfoxide on friend cell differentiation.Biochem Pharmacol 1978;27:1309–13.
Hinder RA, Stein HJ. Oxygen-derived free radicals.N Engl J Med 1991;126:104–6.
Pommier RF, Woltering EA, Milo G, Fletcher WS. Synergistic cytotoxicity between dimethyl sulfoxide and antineoplastics against ovarian cancer in vitro.Surg Forum 1987;38:475–7.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hajarizadeh, H., Lebredo, L., Barrie, R. et al. Protective effect of doxorubicin in vitamin C or dimethyl sulfoxide against skin ulceration in the pig. Annals of Surgical Oncology 1, 411–414 (1994). https://doi.org/10.1007/BF02303814
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02303814