Nadroparine blunts lipopolysaccharide-induced hypothermia and behavioral depression in mice

Despite the use of appropriate antimicrobial therapy and intensive care support, sepsis remains a major cause of morbidity and mortality in surgical clinics. Low-molecular weight heparin treatment may reduce mortality and end-organ failure in sepsis. The purpose of this study was to compare the effects of low-molecular weight heparins such as nadroparine, enoxaparine, and dalteparine on lipopolysaccharide-induced acute phase reaction in mice.

Lipopolysaccharide was injected intraperitoneally to produce a systemic inflammatory response and septic shock-like effects in adult male BALB/c mice. Mices were treated with low-molecular weight heparins (nadroparine, enoxaparine, dalteparine) and unfractioned heparin in different doses and times. Rectal temperature and spontaneous locomotor activity of the mice were evaluated.

Lipopolysaccharide (1 mg/kg, intraperitoneal) produced a hypothermia that occurred 20 minutes after injection. Nadroparine pretreatment (23.75 U/kg, sc) 2 hours before lipopolysaccharide challenge, but not synchronous injection, inhibited the hypothermic response. Pretreatment with equivalent doses of enoxaparine or dalteparine had no effect on the hypothermia. The high dose of lipopolysaccharide (60 mg/kg, intraperitoneal) caused more profound hypothermia and also inhibited spontaneous locomotor activity 24 hours after injection. Synchronous nadroparine administration partially attenuated the hypothermia and significantly abolished the depression of spontaneous locomotor activity.

The results suggest that some low-molecular weight heparins such as nadroparine might be beneficial in high-risk surgical patients because of their potential anti-inflammatory action, in addition to their efficiency in preventing thrombo-embolic complications.