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Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

We investigated the effects of endogenously produced and exogenously applied nitric oxide (NO) on cell proliferation rates and cell cycle regulation in senescent human fibroblasts (WI38). Induction of inducible nitric oxide synthase by tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta inhibited cell proliferation and led to a G1 arrest. These effects were partially reversible by N(G)-monomethyl-arginine (NMA). Addition of the NO donors sodium nitroprusside (SNP) or S-nitroso-N-acetylpenicillamine (SNAP) increased cell proliferation rates as well as the S/G2 fraction. This points to a functional role of NO in cell cycle regulation and cell proliferation in human fibroblasts which depends on the mode of NO generation as well as the culture conditions used.

Characteristic mucosal lesions develop in the small intestine during ischaemia and hypotension. This tissue damage can be further aggravated in the immediate reperfusion phase, presumably secondary to the generation of oxygen free radicals which have been proposed to be generated in this situation through the hypoxanthine-xanthine oxidase system. This was further investigated in the cat small intestine using a standardized regional intestinal hypotension model in which the effects of allopurinol (a xanthine oxidase inhibitor) were compared to those of an exogenous supply of inosine. The grade of mucosal damage, the nucleotide levels, the concentrations of hypoxanthine, total and oxidized glutathione, and of conjugated dienes were measured in the intestinal tissue. The results indicate that oxygen radicals generated by xanthine oxidase are very important, but not the only significant factor in the small intestinal reperfusion damage.