The experimental study of dexamethasone effectiveness in a model of lipopolysaccharide-induced acute lung injury in rats

Aim. To evaluate the efficacy and safety of dexamethasone at various doses in an experimental model of direct acute lung injury (ALI).

Materials and methods. The study was performed on 80 white outbred male rats, in which ALI was modeled by intratracheal administration of lipopolysaccharide. The animals were divided into 4 groups: the control group and three experimental groups (groups 1–3), where the animals were intraperitoneally administered dexamethasone at doses of 0.52, 1.71, and 8.00 mg / kg / day, respectively, for 3 days. A complete blood count, blood biochemistry test, and hemostatic tests were performed to assess the efficacy and safety of dexamethasone on day 3 of the experiment The severity of pulmonary edema was assessed by changes in the lung weight coefficient and the wet / dry weight ratio.

Results. The use of dexamethasone in the ALI model increased the survival of rats in groups 1 and 2 by 35% (p < 0.05), and in group 3 only by 20% compared with control animals. The rat lung weight coefficient and the wet / dry weight ratio when using dexamethasone at all doses studied were equally reduced by an average of 28% (p < 0.05) and 17% (p < 0.05), respectively (p < 0.05). The severity of side effects of dexamethasone (hyperglycemia, hyperproteinemia, hyperkalemia, hypercoagulability, increased activity of creatine phosphokinase in the blood) was dose-dependent and was maximum in group 3 (dexamethasone dose 8.00 mg / kg / day).

Conclusion. The effectiveness of both low (0.52 mg / kg / day) and high (8.00 mg / kg / day) doses of dexamethasone in an experimental model of ALI in rats is characterized by the same anti-edematous effect. Based on the results of the blood tests and the analysis of rat survival, the use of dexamethasone at the lowest dose (0.52 mg / kg / day) should be considered the safest.

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