Matrix metalloproteinase inhibition protects hepatic integrity in hemorrhagic shock

Abstract

Hemorrhagic shock increases cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), and compromises hepatic function and integrity. The production of TNF-alpha involves a cascade reaction regulated by the enzyme TNF-alpha convertase. The purpose of this study was to examine the effects of matrix metalloproteinase inhibitor (MMPI) (British Biotech 1101) in vivo on hepatic integrity in a rat model of hemorrhagic shock. Sprague-Dawley rats (n = 26) were divided as follows: hemorrhagic shock (group 1) and hemorrhagic shock plus MMPI (group 2). TNF-alpha, IL-6, and hepatic membrane potentials (Em) were obtained. The administration of MMPI significantly decreased TNF-alpha levels (P <0.001) and stabilized the membrane potential at -30 mV as compared to the depolarized membrane potential at -20 mV for hemorrhagic shock without MMPI. IL-6 levels were not affected by the MMPI. This study demonstrates that MMPI decreases TNF-alpha levels and protects hepatic integrity in hemorrhagic shock, as evidenced by the stabilization of the membrane potential, independent of the mean arterial pressure. The hepatic protection is closely related to the decrease in TNF-alpha levels seen in the portal circulation.