• Toxicological Research
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• 제11권2호
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• pp.247-252
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• 1995

To evaluate the effect of xanthine oxidase on liver injury by $CCl_4$, liver damage was induced both in allopurinol pretreated rats (500 mg/kg. ip) and control group by twice intraperitoneal injection of $CCl_4$ (0.1 ml/100 g body wt. 50% in olive oil) at interval of one day. Increases in the levels of serum alanine aminotransferase and liver weight/body weight (%) by $CCl_4$ were significantly smaller inallopurinol pretreated rats than in control whereas the hepatic microsomal glucose-6-pholphatase activities were significantly higher in allopurinol pretreated rats than control group by $CCl_4$ treatment. These results indicates that allopurinol pretreatment may reduce the liver damage in $CCl_4$ intoxicated rats. In rats either with $CCl_4$or not, hepatic type O xanthine oxidase activities were significantly reduced by allopurinol pretreatment and the increasing rate of these enzymes to each control was remarkably lower in allopurinol pretreated rats than control. Liver cytosolic protein contents and aniline hydroxylase, aminopyrine demethylase activities were higher in allopurinol pretreated rats than coirol rats when animals were treated with $CCl_4$. On the other hand, neither allopurinol pretreated nor $CCl_4$ treatment caused any significant changes in hepatic superoxide dismutase and catalase activities. Hepatic glutathione contents were higher in $CCl_4$-treated rats than control, but no significant changes were found in both between the allopurinol treated rats and $CCl_4$-treated rats pretreated with allopurinol, and glutathione and glutathione S-transferase activities were significantly reduced in $CCl_4$-treated rats than control whereas these enzyme activities showed on significant change in both between allopurinel treated and $CCl_4$-treated rats pretreated with allopurinol. It is concluded that xanthine oxidase reaction system augment $CCl_4$ induced liver injury via even oxygen free radical system.

• Journal of Plant Biology
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• 제30권2호
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• pp.95-108
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• 1987

Effects of allopurinol (2mM), a specific inhibitor of xanthine oxidase, on the growth and metabolism of llantoin in dark grown Chinese cabbage (Brassica campestris L.) seedlings were investigated. Allopurinol treatment maintained the fresh and dry weights of cotyledons at higher levels, but inhibited the elongation of hypocotyls and roots of the seedlings. Total nitrogen content in the cotyledons decreased at slower rate by allopurinol. Accordingly, the levels of total nitrogen contents in the hypocotyls and roots, were depressed by the inhibitor. In the cotyledons, allopurinol began to elevate RNA levels after day 3, which it did not affect DNA level throughout the experiment. Activities of xanthine oxidase (XO:EC 1.2.3.2), uricase (UO:EC 1.7.3.3) and allantoinase (AL:EC 3.5.2.5) in the cotyledons were examined. The activity of XO was not detected, but the accumulation of xanthine by allopurinol treatment presented an indirect evidence of the existence of XO in the organ. Allopurinol kept UO activity high up to day 2 after sowing and depressed AL activity throughout the experiment. By allopurinol treatment, allantoin content was kept high over the control both in cotyledons and roots, but it was kept low in hypocotyls. The level of allantoic acid in the 3 organs were shown to be depressed by allopurinol. These results suggest that allantoin and allantoic acid produced by the degradation of stored and newly synthesized RNA are transported from the storage tissue to hypocotyls and roots as important nitrogen sources for the development of Chinese cabbage seedlings.

• Preventive Nutrition and Food Science
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• 제3권1호
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• pp.48-55
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• 1998

An acute ethanol load(50mmol/kg , i.p) resulted in an increase in peroxidation and a decrease in the levels of $\alpha$-tocopherol and ascorbate in rat cerebellum. Pretreatement with allopurinol(146$\mu$mol/kg, i.p) prevented the ethnol-induced increment in lipid peroxidation and decrease in $\alpha$-tocopherol content. However, the decrease of ascorbate was of greater magnitude when allopurinol was associated with ethanol. These results suggested that allopurinol. besides its action as a radical scavenger and xanthine oxidase inhibitor, might favor the regeneration of $\alpha$-tocopherol antioxidant acitviity was studied using ${\gamma}$-radiolysis in aerated ethanolic solutions. Even though allopurinol did not react by itself with $\alpha$-hydroxyethyl-peroxyl radicals [H3C-CH(OH)OO] , it enhance the $\alpha$-hydroxyethyl-peroxyl radical scavenging properties of $\alpha$tocopherol. The regeneration of $\alpha$-tocopherol from the $\alpha$-hydroxyethyl-peroxyl radical scavenging properties of $\alpha$-tocophero. The regeneration of $\alpha$-tocopherol from the $\alpha$-tocopherol radical by ascorbate remained as efficient in the presence of allopurinol as in its absence. The effects of allopurinol on the Vitamin E oxidation-reduction mechanism could be involoved in the beneficial effectof allopurinol on the biological cellular damages linked to free radical reactions.

• Toxicological Research
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• 제9권1호
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• pp.23-33
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• 1993

In the present study, the effects of allopurinol on paraquat toxicity were investigated in paraquat-treated rats. The surivals of paraquat-treated rats were increased by allopurinol treatment. The contents of glutathione in liver and kidney were significantly decreased by paraquat, but restored by allopurinol. The activity of xanthine oxidase was significantly reduced but NADH dehydrogenase was not changed by allopurinol teatment. The activities of catalase, SOD and glutathione peroxidase in liver were significantly decreased by paraquat but catalase was restored by allopurinol treatment.

• 대한의생명과학회지
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• 제1권1호
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• pp.37-43
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• 1995

사염화탄소에의한 간손상시 $CCl_4$대사에 xanthine oxidase(XO)가 관련되는지를 규명하기위한 일환으로 allopurinol을 흰쥐 체중 Kg당 50mg을 전처치한다음 $CCl_4$를 투여한 후 처치하여 다음과 같은 결과를 얻었다. $CCl_4$투여로 인한 간조직의 postmitochondria 분획의 XO활성은 allopurinol을 전처치하므로서 현저히 감소되었으나 투석한 경우에는 오히려 증가되었으며 type D로부터 type O로의 전환율은 감소되었다. 또한, 투석한 간조직의 XO를 반응속도적인 측면에서 관찰해 볼 때 allopurinol을 전처치후 $CCl_4$투여군이 $CCl_4$단독투여 군보다 Vmax가 크게 나타났다. $CCl_4$투여로 인한 체중당 간무게의 증가율과 혈청 alanine aminotransferase활성증가율은 allopurinol을 전처치하므로서 저하되었다. 한편 $CCl_4$투여로 인한 간조직중 aniline hydroxylase및 glucose 6 phosphatase활성 감소율은 allopurinol을 전처치하므로서 저하되었다. 이상의 실험결과를 종합하여 볼때 실험동물에 $CCl_4$와 allopurinol을 병행 투여시 allopurinol이 사염화탄소에 의한 간손상을 억제시키는 현상은 XO와 사염화탄소 대사간에 관련성이 있음을 시사해주고 있다.

• Journal of Oral Medicine and Pain
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• 제23권3호
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• pp.257-261
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• 1998

Angiokeratoma is a cutaneous vascular disorder that occurs at any sites as trunk,extremities, fingers and toes etc. Although solitary or multiple cutaneous lesions have been reported, oral lesions have been very care. A 72-year-old man who had an exophtic, essile mass with dark red, black colored which located on buccal mucosa, was treated with excisional biopsy. He had no specific systemic history except for the medication of allopurinol, for treatment of gout since 10 years. Final diagnosis was determined as angiokeratoma by evaluation of clinical and histopathological finding, and the lesion has not been recurred for two months by decrease of allopurinol. It has been emphasized that the relationship between oral mucosal disease and the complication of allopurinol. Allopurinol is widely used for gout treatment, which we will report a case on the allopurinol-associated angiokeratoma in the oral mucosa.

• 동의생리병리학회지
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• 제20권4호
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• pp.980-984
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• 2006

In order to examine the effect of oxygen free radicals on the vascular endothelial cells, cell viability was measured by XTT assay after bovine pulmonary vascular endothelial cell line(BPVEC) was treated only with hydrogen peroxide. In addition, the antioxidant effect of allopurinol on cells treated with hydrogen peroxide was examined by colormetric assay. in this study, the BPVEC treated with hydrogen peroxide showed the significantly decreased cell viability compared with control. Whereas, the viability of cells treated with hydrogen peroxide and allopurinol has significantly increased when compared with that of cells treated only with hydrogen peroxide. These results suggested that hydrogen peroxide, one of the oxygen free radicals showed cytotoxic effect and allopurinol has protective effect on oxygen free radical-induced cytotoxicity.

• Translational and Clinical Pharmacology
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• 제25권2호
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• pp.63-66
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• 2017

Allopurinol-induced severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are reportedly associated with the $HLA-B^{\star}58:01$ genotype. Three patients who developed SCARs after allopurinol administration were subjected to HLA-B genotyping and lymphocyte activation test (LAT) to evaluate genetic risk and to detect the causative agent, respectively. All three patients given allopurinol to treat gout were diagnosed with DRESS syndrome. Symptom onset commenced 7-24 days after drug exposure; the patients took allopurinol (100-200 mg/d) for 2-30 days. HLA-B genotyping was performed using a polymerase chain reaction (PCR)-sequence-based typing (SBT) method. All patients had a single $HLA-B^{\star}58:01$ allele: $HLA-B^{\star}13:02/^{\star}58:01$ (a 63-year-old male), $HLA-B^{\star}48:01/^{\star}58:01$ (a 71-year-old female), and $HLA-B^{\star}44:03/^{\star}58:01$ (a 22-year-old male). Only the last patient yielded a positive LAT result, confirming that allopurinol was the causative agent. These findings suggest that patients with $HLA-B^{\star}58:01$ may develop SCARs upon allopurinol administration. Therefore, HLA-B genotyping could be helpful in preventing serious problems attributable to allopurinol treatment, although PCR-SBT HLA-B genotyping is time consuming. A simple genotyping test is required in practice. LAT may help to identify a causative agent.

• 대한의생명과학회지
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• 제12권4호
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• pp.451-455
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• 2006

It is demonstrated that inorganic mercury has cytotoxic effect on glial cells. Recently, oxygen radicals is involved in methylmercuric chloride (MMC)-induced cytotoxicity. But, the toxic mechanism of MMC is left unknown. The purpose of this study was to examine the cytotoxicity of MMC on $C_6$ glioma cells. The cytotoxicy was measured by cell viability using XTT assay in $C_6$ glioma cells. Colorimetric assay is regarded as a very sensitive screening method for the determination of the cell viability on various agents. In this study, MMC decreased cell viability according to the dose- and time dependent manners after $C_6$ glioma cells were grown with various concentrations of MMC for 48 hours. In the protective effect of allopurinol on MMC-induced cytotoxicity, allopurinol was effective in the prevention of MMC-induced cytotoxicity in these cultures. These results suggest that MMC has highly cytotoxic effect on $C_6$ glioma cells by the decrease of cell viavility, and free radical scavenger such as allopurinol was effective on organic mercury-induced cytotoxicity in these cultures.

• Applied Microscopy
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• 제25권3호
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• pp.51-62
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• 1995

It has been well known that ischemia and reperfusion injury to skeletal muscle following an acute arterial occlusion causes significant morbidity and mortality. The skeletal muscle, which contains high energy phosphate compounds, has ischemic tolerance. During the ischemia, the ATP is catalyzed to hypoxanthine anaerobically and hypoxanthine dehydrogenase is converted to xanthine oxidase. During reperfusion, the hypoxanthine is catalyzed to xanthine by xanthine oxidase under $O_2$, presence and that results in production of cytotoxic oxygen free radicals. These cytotoxic free radicals, $O_2^-,\;H_{2}O_2,\;OH^-$, are toxic and make lesions in skeletal muscle during reperfusion. The authors perform the present study to investigate the effects of allopurinol, the inhibitor of xanthine oxidase, on reperfused ischemic skeletal muscles by observing the ultrastructural changes of the muscle fibers. A total of 48 healthy Sprague-Dawley rats weighing from 200 g to 250 g were used as experimental animals. Under urethane(3.0mg/kg., IP) anesthesia, lower abdominal incision was done and the left common iliac artery were ligated by using vascular clamp for 1, 2 and 6 hours. The left rectus femoris muscles were obtained at 6 hours after the removal of vascular clamp. In the allopurinol pretreated group, 50mg/kg of allopurinol was administered once a day for 2 days and before 2 hours of ischemia. The specimens were sliced into $1mm^3$ and prepared by routine methods for electron microscopic observations. All preparations were stained with uranyl acetate and lead citrate, and then observed with Hitachi -600 transmission electron microscope. The results were as follows: 1. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats, decreased glycogen particles and electron density of mitochondrial matrix and dilated terminal cisternae are seen. In 2 hours ischemia/6 hours repersed rectus femoris muscles of rats, mitochondria with electron lucent matrix, irregularly dilated triad and spheromembranous bodies are observed. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats, irregularly arranged myofibrils, and many spheromembranous bodies, fat droplets and lysosome are seen. 2. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, decreased glycogen particle and dilated cisternae of sarcoplasmic reticulum and triad are observed. In 2 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol decreased electron density of mitochondrial matrix and spheromembranous bodies are seen. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, mitochondria with electron lucent matrix, spheromembranous bodies and dilated cisternae of sarcoplasmic reticulum and terminal cistern are observed. The results suggest that the allopurinol attenuates the damages of the skeletal muscles of rats during ischemia and reperfusion.