Lobe-specific heterogeneity and matrix metalloproteinase activation after ischemia/reperfusion injury in rat livers.

Background and aim: In the last years, the effects of partial-hepatic ischemia/reperfusion (I/R) injury have been concentrated on the damage to the ischemic-lobe, whereas few data are available on the non-ischemic lobe. This study investigated whether acute liver I/R does affect non-ischemic lobe function via modulation of extracellular matrix remodeling. Materials and methods: Fourteen male Sprague-Dawley rats underwent left lateral- and median-lobe ischemia for 30 min and subsequent reperfusion for 60 min or sham operation. After reperfusion, blood samples and hepatic biopsies from both the ischemic- (left-lobe, LL) and the non-ischemic lobe (right-lobe, RL) were collected. Serum hepatic enzymes and TNF-alpha, tissue matrix metalloproteinases (MMP-2, MMP-9), malondialdehyde (MDA), myeloperoxidase (MPO) and liver morphology were evaluated. Results: Liver I/R injury was confirmed by altered increased hepatic enzymes and TNF-alpha measured at the end of reperfusion. I/R induced an altered morphology and an increase in MMP-2 and MMP-9 activity not only in left-ischemic lobe (LL) but also in the right-non-ischemic (RL) lobe. A lobar difference was detected for MDA formation and MPO activity both in sham and I/R submitted rats, with higher levels in the left-lobe for both groups. Conclusions: This study indicates that a moderate acute hepatic I/R injury is able to increase MMPs activity not only in the ischemic region, but also in the nonischemic lobe. This event is probably TNF-alpha-mediated but is not associated with oxidative damage in the right non-ischemic lobe, despite early signs of tissue damage. The previously described lobe-specific heterogeneity of the liver has been confirmed and supported by the present study suggesting that the random sampling of liver tissue should be avoided.