Matrix metalloproteinase inhibition protects hepatic integrity in hemorrhagic shock

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 regulat ed by the enzyme TNF-alpha convertase. The purpose of this study was to exa mine the effects of matrix metalloproteinase inhibitor (MMPI) (British Biot ech 1101) in vivo on hepatic integrity in a rat model of hemorrhagic shock. Sprague-Dawley rats (n = 26) were divided as follows: hemorrhagic shock (g roup 1) and hemorrhagic shock plus MMPI (group 2). TNF-alpha, IL-6, and hep atic membrane potentials (Em) were obtained. The administration of MMPI sig nificantly decreased TNF-alpha levels (P < 0.001) and stabilized the membra ne 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 b y the MMPI. This study demonstrates that MMPI decreases TNF-<alpha> levels and protects hepatic integrity in hemorrhagic shock, as evidenced by the st abilization of the membrane potential, independent of the mean arterial pre ssure. The hepatic protection is closely related to the decrease in TNF-alp ha levels seen in the portal circulation.