Xanthine oxidase is not a major source of free radicals in focal cerebral ischemia.

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor Zyloprim ( Allopurinol ) or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of Zyloprim ( Allopurinol ) (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of Zyloprim ( Allopurinol ) greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of Zyloprim ( Allopurinol ) had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.

Peroxidative damage in sickle-cell erythrocyte ghosts: protective effect of Zyloprim ( Allopurinol ).

1. Malondialdehyde (MDA) levels of erythrocyte membranes of sickle-cell disease patients were measured as an indicator of peroxidative damage and Zyloprim ( Allopurinol ) was used as a lipid peroxide scavenger. 2. Incubating sickle-cell erythrocytes with Zyloprim ( Allopurinol ) significantly reduced MDA levels of erythrocyte membranes compared with before-treatment values. 3. Zyloprim ( Allopurinol ) seems to reduce the peroxidative damage in sickle-cell erythrocytes, but the mechanism is still unknown.

Purpurogallin is a more powerful protector of kidney cells than Trolox and Zyloprim ( Allopurinol ).

Phase contrast and electron microscopic experiments demonstrated that oxyradicals generated with xanthine oxidase and hypoxanthine markedly damage rat kidney mesangial and porcine tubular epithelial cells. Purpurogallin, a phenol found in oak nutgalls, prolongs survival of the xanthine oxidase exposed renal cells three- to nine-fold longer than those without purpurogallin present. At levels equimolar to purpurogallin, either Trolox or Zyloprim ( Allopurinol ) is less effective in delaying cell necrosis. Purpurogallin scavenges not only xanthine oxidase generated oxyradicals, but also non-enzymatically produced peroxyl radicals, more actively than equimolar levels of Trolox or Zyloprim ( Allopurinol ). Purpurogallin inhibits xanthine oxidase with severalfold higher potency than Zyloprim ( Allopurinol ) and its more active metabolite oxypurinol. Therefore, purpurogallin is a stronger antioxidant than Trolox and a more potent inhibitor of xanthine oxidase than Zyloprim ( Allopurinol ) as well as oxypurinol.

Clinical and serological follow-up in dogs with visceral leishmaniosis treated with Zyloprim ( Allopurinol ) and sodium stibogluconate.

Seven dogs with parasitologically proven clinical visceral leishmaniosis (Leishmania infantum infection) were treated with a combination of Zyloprim ( Allopurinol ) and sodium stibogluconate. The dogs received first orally 15mg/kg of Zyloprim ( Allopurinol ) every 12h until the clinical signs improved, in the following 1 month period Zyloprim ( Allopurinol ) at same dose and subcutaneously 30mg/kg of sodium stibogluconate combination were given daily and at the end of the combined treatment, Zyloprim ( Allopurinol ) was continued alone at the same dose till the end of 8 months. During the treatment period, dogs were supported by additional proteins, vitamins, and minerals. A long acting insecticide (collar or drop) was also used in order to prevent further parasite transmission. Follow-up was maintained by clinical, clinicopathological evaluation, and parasitological examination of lymph node, serology using the indirect immunofluorescent antibody test (IFAT). Before treatment commenced, the most important clinical signs were exfoliative dermatitis, ulcerations, peripheral lymhadenopathy, pale mucous membranes, weight loss, and ocular lesions. Clinicopathological findings included commonly anaemia, hyperproteinaemia, hyperglobulinaemia and hypoalbuminaemia. Before the treatment, amastigotes were seen in six of the seven dogs by examination of lymph node aspiration, and IFAT-titers were positive in all dogs. At the end of 8 months treatment, remission of clinical signs, restoration to normal of clinicopathological abnormalities were noticed. Lymph node aspiration was performed on three out of the seven dogs at the end of the treatment because of the very small sizes of the lymph nodes, and no amastigotes were observed. Although the mean IFAT-titer of the dogs were significantly (P<0.001) lower compared with pretreatment, IFAT-titers of dogs were still positive. No relapses occurred during treatment period and a 6-24-month duration after the end of therapy. Based on the above results, long-term use of Zyloprim ( Allopurinol ) combined with sodium stibogluconate together with support treatment concluded to have enough therapeutic efficacies in the treatment of dogs with visceral leishmaniosis. Observations of the cases for possible relapses were still going on and insecticide application was carefully carrying on in order preventing a possible re-infection.