PROTECTIVE EFFECT OF DOXORUBICIN IN VITAMIN-C OR DIMETHYL-SULFOXIDE AGAINST SKIN ULCERATION IN THE PIG

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.