Melatonin and a 21-Aminosteroid Attenuate Shock after Hemorrhage but Differentially Affect Serum Cytokines

Autor: Sullivan, Dennis J., Shelby, Jane, Shao, Yuanlin, Affleck, David G., Hinson, Douglas M., Barton, Richard G.
Zdroj: Journal of Surgical Research; July 1996, Vol. 64 Issue: 1 p13-18, 6p
Abstrakt: Melatonin and 21-aminosteroids (lazaroids) are potent antioxidants and may attenuate the increased membrane permeability associated with profound shock. Our purpose was to test the effect of melatonin and a lazaroid (U74389-G) on cytokine production and fluid requirements after shock. Methods: Male C3H/HeN mice, 20–25 g, were hemorrhaged via a femoral artery catheter to a mean arterial pressure of 35 ± 5 mm Hg, which was maintained for 1 hr, and then resuscitated with shed blood and crystalloid (2× vol of shed blood). Experimental mice received melatonin at 10 or 50 mg/kg, U74389-G at 3 mg/kg, or vehicle iv upon resuscitation, and blood was returned at 0.1 cc/min and crystalloid at 0.05 cc/min. The percentage of total crystalloid required to reach stabilization (mean arterial pressure remaining within 2 mm Hg for 5 min) was recorded. Animals were sacrificed at 1 hr postshock. Serum and anti-CD3-stimulated splenocyte culture supernatants were assayed for interleukin-6 (IL-6) and γ-IFN by ELISA. Results: Mice receiving lazaroid or melatonin (50 mg/kg) required significantly less fluid to reach stabilization, with lazaroid-treated animals requiring 24 ± 1% and melatonin-treated animals requiring 28 ± 2% of total crystalloid compared to 40 ± 3% for untreated animals. Melatonin-treated mice (50 mg/kg) had lower serum IL-6 levels (368 ± 154 vs 1078 ± 146 pg/ml) and lazaroid-treated mice had lower γ-IFN levels (7 ± 6 vs 52 ± 15 pg/ml) compared to those of the untreated group (P< 0.05). There were no differences in splenocyte cytokine production. Conclusions: Treatment with lazaroid and melatonin both reduced postshock fluid requirements. Melatonin reduced serum IL-6 levels, while lazaroid reduced serum γ-IFN levels, suggesting different mechanisms of action.
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