Enhanced post-ischemic liver injury in iNOS-deficient mice: A cautionary note

The objective of this study was to assess the role of inducible nitric oxid e synthase (iNOS) in ischemia and reperfusion (I/R)-induced liver injury, W e found that partial hepatic ischemia involving 70% of the liver resulted i n a time-dependent increase in serum alanine aminotransferase (ALT) levels at 1-6 h following reperfusion. Liver injury at 1, 3, and 6 h post-ischemia was not due to the infiltration of neutrophils as assessed by tissue myelo peroxidase (MPO) activity and histopathology. iNOS-deficient mice subjected to the same duration of ischemia and reperfusion showed dramatic and signi ficant increases in liver injury at 3 but not 6 h following reperfusion com pared to their wild type controls. Paradoxically, iNOS mRNA expression was not detected in the livers of wild type mice at any point during the reperf usion period and pharmacological inhibition of iNOS using L-N-6(iminoethyl) -lysine (L-NIL) did not exacerbate post-ischemic liver injury at any time p ost-reperfusion. These data suggest that iNOS deficiency produces unanticip ated genetic alterations that renders these mice more sensitive to liver I/ R-induced injury. (C) 2001 Academic Press.