The effect of dehydroepiandrosterone on oxygen-dependent microbicidal activity of blood leukocytes in zymosan peritonitis in old rats

The purpose of the present work was to study effects of dehydroepiandrosterone (DHEA) on the oxygen-dependent microbicidal activity of blood leukocytes. The studies were performed on male white nonlinear rats aged 3-6 months (young rats) and adult animals over 1.5 years old (old rats) using an experimental model of zymosan peritonitis. DHEA was administered subcutaneously to old animals on the daily basis (a total of 4 injections of 2 mg/kg body weight, the last injection 24 hours before the end of the experiment). Rats of similar age served as controls and received DHEA solvent (officinal olive oil) according to the same time regimen. 12 hours before the end of the experiment, the animals were administered a sterile suspension of zymosan A intraperitoneally at a dose of 50 mg/kg. The oxygen-dependent microbicidal activity of blood leukocytes was assessed by luminol-dependent chemiluminescence using opsonized and non-opsonized zymosan at concentrations of 15 μg/mL, 150 μg/mL and 1500 μg/mL.

In old male rats, compared to young ones, the chemiluminescence indexes showed a statistically significant increase when blood leukocytes were stimulated with both opsonized and non-opsonized zymosan. Administration of DHEA to old male rats leads to a pronounced decrease in chemiluminescence in samples at all concentrations of opsonized zymosan. When leukocytes of old animals are stimulated with non-opsonized zymosan in vitro, a statistically significant increase in the production of reactive oxygen species was observed, being more pronounced at lower concentrations of inducing agent (15 μg/mL and 150 μg/mL). Meanwhile, this effect was canceled at high concentrations of zymosan. The level of spontaneous chemiluminescence, reflecting in vivo cell activation, was higher in old rats treated with DHEA compared to young animals. The direction of changes in the production of reactive oxygen species in samples with low concentrations of the in vitro activation was similar to the effects of DHEA in old rats tested for spontaneous chemiluminescence. In general, our studies confirm the pronounced immunomodulatory activity of DHEA. In general, we have found that aging of male rats leads to pronounced pro-inflammatory activation of reactive oxygen species produced by blood leukocytes at the peak of inflammation induced by zymosan injections. Administration of DHEA to old male rats significantly reduced the production of reactive oxygen species by blood leukocytes, when the cells were in vitro activated by opsonized zymosan, but stimulates production of oxygen radicals in the samples without zymosan, as well as upon exposition to non-opsonized zymosan at concentrations of 15 μg/mL and 150 μg/ mL.