The pineal gland hormone melatonin improves survival in a rat model of sepsis/shock induced by zymosan A.

Abstract

Melatonin has demonstrated protective effects in severe sepsis/shock in the animal model. Zymosan A causes inflammation and shock leading to death in rats. We hypothesized that daily afternoon melatonin administration would improve rat survival after an intraperitoneal (IP) zymosan injection. Adult male rats, maintained on a 12L:12D photoperiod, received a single IP injection of either zymosan (500 mg/kg) or paraffin vehicle at 1200 hours. At 1700 hours and daily thereafter, zymosan-injected rats received subcutaneous injections of either melatonin (0.8 mg/kg) or saline (SAL). Any surviving animals were killed on day 10 to obtain wet organ weights. Three independent experiments produced similar results. In each zymosan+SAL group, all animals died by day 4. In the melatonin-treated groups combined, 33/45 rats survived (73.33%, P<.00002). Posthumous body weight was greater in melatonin-treated animals compared with the zymosan+SAL groups (P<.001). Mean splenic weight in the melatonin-treated groups was twice that of the control groups (P<.001). Melatonin administered in the late afternoon after a lethal dose of zymosan significantly improved animal survival. Melatonin has no known adverse effects in humans and may represent a novel treatment for sepsis/shock.