Free radical scavengers to prevent reperfusion injury following experimental warm liver ischaemia. Is there a real physiological benefit?
Free radical scavengers have been utilized to prevent the consequences of ischemia, however, results do not seem conclusive. In our study we analyzed the blood flow, function, and histology of rat liver tissue after warm liver ischemia, in order to assess the effect of free radicals in liver reperfusion injury. N-acetyl cysteine (NAC), tocopherol, allopurinol, and superoxide dismutase (SOD), pharmacological agents expected to protect from injury mediated by free radicals, were investigated. Laser Doppler flowmetry and photometry were utilized to measure post-ischemic microcirculatory changes as an expression of ischemia-reperfusion injury in a model of segmental liver ischemia in the rat, with an ischemic time of 45 min. Galactose elimination capacity, ALT and histology were used to assess the functional and morphological consequences of ischemia after 24 h of reperfusion. The overall mean blood flow over 1 hour after reperfusion was of 33.9% (SD 11.2) of the normal, non-ischemic control. NAC (31.2% SD 10.9) did not show any protective effect and in some cases the effect seemed to be negative. Tocopherol (41.7% SD 5.1) marginally improved post ischemic liver tissue blood flow. Treatment with allopurinol did not show any beneficial effects (37.5% SD 14.2). Only animals treated with SOD showed an improvement of the post ischemic liver microcirculation (57.9% SD 14.4)(P < 0.001) and function. Only SOD produced statistically significant differences in galactose elimination capacity, compared with those of the ischemic control group. This moderately protective effect of SOD is encouraging, however, the relevance of all these compounds in a broader pathophysiological setting remains unproven.
Chavez-Cartaya
R
R
Department of Surgery, Addenbrookes Hospital, Cambridge, United Kingdom.
Jamieson
N V
NV
Ramirez
P
P
Marin
J
J
Pino-Chavez
G
G
D000111:Acetylcysteine / Q000627:therapeutic use; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005690:Galactose / Q000493:pharmacokinetics; D007511:Ischemia / Q000150:complications*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000627:therapeutic use
D016166:Free Radical Scavengers; D014810:Vitamin E; D000493:Allopurinol; D013482:Superoxide Dismutase; D000111:Acetylcysteine; D005690:Galactose