Research Shows Steroids May Slow Generation of Free Radicals

WASHINGTON, D.C. -- Corticosteroid drugs, administered to fight inflammation and suppress the immune response, may produce their results by slowing the generation of damaging free radicals, researchers at the University at Buffalo reported today (June 16, 1995).

"This study shows a new effect of steroids," said Paresh Dandona, M.D., Ph.D., a specialist in endocrinology at UB and Millard Fillmore Hospital in Buffalo and lead investigator on the study. "We observed a sharp fall in oxygen free radical generation. This action may account for the effectiveness of steroids as anti-inflammatories and immunosuppressants."

Results of the study were reported at the annual meeting of the Endocrine Society.

Oxygen free radicals are known to induce tissue damage and inflammation. Since steroids are used routinely to treat these conditions, the researchers investigated whether steroids administered intravenously suppress production of free radicals, which would identify one possible pathway of the drug's action.

To test this theory, they administered a single dose of 100 mg. or 300 mg. of hydrocortisone to 14 volunteers. Eight received the higher dose, six the lower.

Blood samples were collected before the injection and at several intervals afterward. Concentrations of free radicals and steroids were assessed in all samples.

Results showed that free-radical generation dropped by 95 percent within two hours of administering the higher steroid dose. Significant reductions occurred within 1/2 hour. At 24 hours, production of free radicals had increased, but still remained lower than at baseline.

The lesser steroid dose cut free-radical generation by 75 percent within one hour. At eight hours, the concentration had returned to baseline.

Dandona said patients in the intensive care unit routinely receive high doses of cortisone, and that if further research confirms the results of this study, the drug could be administered at regular intervals to achieve maximum anti-inflammatory effect.

In a separate series of laboratory experiments, the researchers showed that the same steroid doses administered to volunteers also inhibited generation of free radicals in cells chemically induced to produce the renegade molecules.

Other members of the research team were Kuldip Thusu, doctoral candidate working with Dandona; Raheela Hafeez, clinical research fellow; and John Love and Usha Khurana, research scientists at Millard Fillmore Hospital.