Metalloproteinase activity in myocardium or rats exposed to endotoxin. Itsinhibition with doxycycline

Background: The ventricular dysfunction of endotoxic shock could be seconda ry to the activity of myocardial metalloproteinases that degrade collagenou s study if the effect of endotoxemia on myocardial metalloproteinase activi ty can be inhibited with doxcycyclin. Marterial and methods: Left ventricul ar metalloproteinase activity was studied in four groups of rats. Group 1 r eceived intraperitoneal dextrose in water, group I received 8 mg/kg intrape ritoneal E coli endotoxin, group 3 received 60 mg/kg/day doxycycline for th ree days and group 4 received doxycycline and E coli endotoxin. Enzymatic a ctivity was measured by Western Blot and zymography. Results: Zymography sh owed a higher metalloproteinase 2 (49%) and 9 (100%) activity in rats treat ed with endotoxin, when compared with control rats. In group 4 doxycycline reduced the activity of metalloproteinases 2 and 9 by 71% and 63% respectiv ely, as compared with group 3. Western blot showed a 50% increase in the ex pression of metalloproteinase 1 in rats treated with endotoxin, that was re duced by 64% with the use of doxycycline. Conclusions: Endotoxin administra tion increases myocardial metalloproteinases and doxycyclin inhibits this a ctivation. Therefore, doxycyclin could reduce the degradation of myocardial fibrillar collagen and ventricular dysfunction of endotoxic shock.