Inhibitory Effect of Hydrocortisone on Adriamycin-induced Tissue Necrosis

ABSTRACT

The objective of this study was to clarify the different inhibitory effects against necrosis according to the injection time of hydrocortisone on adriamycin extravasated wounds. The extravasation of chemotherapeutic agents yields severe inflammatory responses, crust formation, skin necrosis, and ulceration. Thus, many studies on the prevention and alleviation of this tissue injury have been made. However, a comparative study on the inhibitory effect of antidots according to the injection time after extravasation of chemotherapeutic agents has not yet been made. We compared the effect of hydrocortisone succinate on adriamycin-induced tissue necrosis according to its injection time. Sixty mature male Sprague-Dawley rats were divided into 6 groups and each group contained 10 rats. Administration of adriamycin(1.0mg/ml) 0.5ml by subcutaneous injection on the dorsal side of the rats was followed by injection of hydrocortisone succinate(20mg/ml) 0.5ml on the same site according to a time protocol. Group 1(the co-ntrol group) adriamycin injection only; gorup 2(the normal saline group) injection of normal saline 30 minutes after adriamycin injection; group 3 injection of hydrocortisone 30 minutes after adriamycin injection; group 4 injection of hydrocortisone 6 hours after adriamycin injection; group 5 injection of hydrocortisone one day after adriamycin injection; group 6 injection of hydrocortisone 3 days after adriamycin injection. Mean areas of ulcer, measured in mm2, which developed 4 week after adriamycin injection were as follows; group 1 (the control group) 67.3; group 2(the normal saline group)44.8; group 3 12.9; group 4 18.9; group 5 46.7; group 672.0. Significant differences among the groups were noted. The groups which received hydrocortisone injection showed smaller ulcers compared to the control group or the normal saline group. As well, earlier injection time correlated with smaller ulcer formation. These findings showed the inhibitory effect of hydrocortisone succinate on tissue damage caused by adriamycin, as well as the increased effectiveness of the inhibitory effect when earlier injections were made. An analysis of this study can be applied in clinical situations for extravasation of adriamycin by administering proper agents such as hydrocortisone succinate. The administration of these agents will also help to minimize tissue necrosis.