Actividad de las metaloproteinasas en el miocardio de ratas sometidas a endotoxina y su inhibición con doxiciclina / Metalloproteinase activity in myocardium of rats exposed to endotoxin: its inhibition with doxycycline

RESUMO

Background: The ventricular dysfunction of endotoxic shock could be secondary to the activity of myocardial metalloproteinases that degrade collagenous matrix. Metalloproteinase activity can be inhibited with doxycycline in some tissues. Aim: To study if the effect of endotoxemia on myocardial metalloproteinase activity can be inhibited with doxycycline. Material and methods: Left ventricular metalloproteinase activity was studied in four groups of rats. Group 1 received intraperitoneal dextrose in water, group 2 received 8 mg/kg intraperitoneal E coli endotoxin, group 3 received 60 mg/kg/day doxycycline for three days and group 4 received doxycycline and E coli endotoxin. Enzymatic activity was measured by Western Blot and zymography. Results: Zymography showed a higher metalloproteinase 2 (49 percent) and 9 (100 percent) activity in rats treated with endotoxin, when compared with control rats. In group 4, doxycycline reduced the activity of metalloproteinases 2 and 9 by 71 percent and 63 percent respectively, as compared with group 3. Western blot showed a 50 percent increase in the expression of metalloproteinase 1 in rats treated with endotoxin, that was reduced by 64 percent with the use of doxycycline. Conclusions: Endotoxin administration increases myocardial metalloproteinases and doxycyclin inhibits this activation. Therefore, doxycyclin could reduce the degradation of myocardial fibrillar collagen and ventricular dysfunction of endotoxic shock