No evidence for a protective effect of ascorbic acid on free radical generation and liver injury after hemorrhagic shock in rats.
Oxygen free radicals have been shown to be implicated in ischemic tissue injury, and free radical-induced reactions may also play an important role in the pathophysiology of circulatory shock. The present study was designed to investigate the potential use of ascorbic acid as an exogenous antioxidant on the liver's recovery from hemorrhagic shock in situ. Rats (fasted overnight) were subjected to 60 min of hemorrhagic shock (HS) (mean arterial pressure = 40 mmHg) under pentobarbital anesthesia, followed by retransfusion of the shed blood. One-half of the animals (n = 6) were injected with 10 mg/kg of ascorbic acid prior to induction of shock, while untreated animals (n = 6) received the same volume of saline solution. in untreated animals, systemic plasma levels of malondialdehyde rose from 1.07 +/- .08 during normotension (NT) to 1.36 +/- .18* 60 min after resuscitation (RS), documenting oxygen free radical-induced lipid peroxidation. Accordingly, plasma levels of alanine aminotransferase (16.5 +/- 2.5; 34.9 +/- 12.3*; 105.8 +/- 68.7* U/L; NT/HS/RS) and ammonia (127 +/- 40; 532 +/- 160*; 304 +/- 244* micrograms/dL) rose significantly during the experiment. Hepatic ATP content of the liver fell from 4.8 +/- .83 to .56 +/- .27* after HS and recovered partially to 2.7 +/- 1.6* mumol/g after RS. Leukocyte infiltration in the liver, indicated by tissue levels of myeloperoxidase, remained constant during HS but rose during RS (37.9 +/- 18.5; 38.6 +/- 16.4; 81.4 +/- 30.7*, arbitrary units), thus documenting an inflammatory reaction after HS. In the ascorbic acid group, plasma levels of malondialdehyde were comparable to those of untreated animals after RS, as were enzyme concentrations and ammonia. No differences were observed with regard to the tissue concentrations of ATP or myeloperoxidase. Mean arterial blood pressure as well as liver tissue perfusion, as measured by Laser Doppler flowmetry, did not show significant differences between the groups. It was concluded that, although an effect of oxygen free radicals on liver tissue could be found during and after HS, treatment with ascorbic acid alone, in our model, failed to ameliorate the recovery of the animals upon resuscitation (values are mean +/- SD; *, p < .05 vs. NT; one-way ANOVA).
Minor
T
T
Institute for Experimental Medicine, University of Cologne, FR Germany.
Niessen
F
F
Klauke
H
H
Isselhard
W
W
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000641:Ammonia / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism*; D006439:Hemodynamics; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009195:Peroxidase / Q000032:analysis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism
D005609:Free Radicals; D008315:Malondialdehyde; D000641:Ammonia; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D000410:Alanine Transaminase; D001205:Ascorbic Acid