To determine whether oxygen free radicals are responsible for the pathogenesis of the cholestasis induced by ligation of common bile duct (CBD) variables which reflect the hepatic function in the serum, the amount of superoxide radical production, and xanthine oxidase(XO) activity were studied. The activity of serum alanine aminotransferase, bilirubin level in the serum and the amount of superoxide radical production were lower in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Abnormalities of the microscopic structures were reduced in a CBD ligation with allopurinol treated group than in a CBD ligation without allopurinol treated group. Allopurinol, an inhibitor of XO, prevented the hepatic damage induced by CBD ligation through the inhibition of XO. These experiments demonstrate that oxygen free radicals are responsible for the pathogenesis of the cholestatic liver.
Allopurinol/*pharmacology ; Animal ; Bile Ducts ; Cholestasis/*pathology ; Enzyme Inhibitors/*pharmacology ; Free Radicals ; Ligation ; Liver/*pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Superoxides/metabolism ; Xanthine Oxidase/analysis/*antagonists & inhibitors

OBJECTIVETo investigate the correlation of the ultrasonographic appearance of different degrees of experimentally induced acute unilateral testicular ischemia with the protective effect of allopurinol.

METHODSForty-two male white rabbits were equally randomized into 7 groups: sham-operation control, ischemic A, B and C, and treatment D, E and F. Models of different degrees of unilateral testicular ischemia were established in the ischemic and treatment groups under the dynamic observation by color Doppler ultrasound. The ischemic testes showed slightly decreased homogeneous echoes and flow signals in groups A and D, obviously decreased heterogeneous echoes and flow signals in groups B and E, and radial or fragmental low-echo areas and disappearance of flow signals in groups C and F. The ischemic groups received reperfusion after the appearance of the above ultrasonographic changes, while the treatment groups following the intraperitoneal injection of allopurinol at 200 mg/kg. Contrast-enhanced ultrasonography (CEUS) was performed on the bilateral testes before and 3 days after the reperfusion. After 3 days of breeding, the histological changes and malondialdehyde (MDA) contents of the ischemic testes were observed, and the correlation was analyzed between the protective effect of allopurinol and the ultrasonographic appearance of different degrees of acute unilateral testicular ischemia.

RESULTSCEUS showed fast wash-in and fast wash-out in the sham-operation control group, slow wash-in and slow wash-out in groups A and B and extensive central filling defect in group C before the reperfusion. Fast wash-in and slow wash-out were observed in all the ischemic groups 3 days after the reperfusion, most obviously in group C. Groups D, E and F exhibited the same CEUS appearance as A, B and C before and 3 days after the reperfusion. Johnsen's scores were significantly increased in groups D (9.10 +/- 0.23) and E (7.03 +/- 0.20) in comparison with A (8.53 +/- 0.22) and B (5.82 +/- 0.33) (P < 0.05), but with no significant differences between C (2.30 +/- 0.53) and F (2.45 +/- 0.33) (P > 0.05). The rates of apoptosis were significantly decreased in groups D ([1.68 +/- 0.43]%) and E ([12.53 +/- 0.59]%) compared with A ([7.12 +/- 0.84]%) and B ([20.87 +/- 1.59]%) (P < 0.05), but with no significant differences between C ([52.93 +/- 2.62 ]%) and F ([51.23 +/- 2.53 ]%) (P > 0.05). Significant decreases of MDA contents in the ischemic testes were observed in groups D ([0.64 +/- 0.05] nmol/mg prot), E ([1.59 +/- 0.06] nmol/mg prot) and F ([3.10 +/- 0.17] nmol/mg prot) in comparison with A ([1.38 +/- 0.07] nmol/mg prot), B ([2.11 +/- 0.08] nmol/mg prot) and C ([3.25 +/- 0.14] nmol/mg prot) (P < 0.05).

CONCLUSIONAllopurinol contributes to the recovery of spermatogenesis when testicular ischemia is sonographically shown to be mild or moderate, but produces no significant effect when it is shown to be severe. Ultrasonography helps to choose the right therapy of testicular torsion and predict spermatogenesis of ischemic testes after reperfusion.

Allopurinol ; pharmacology ; Animals ; Disease Models, Animal ; Ischemia ; diagnostic imaging ; Male ; Rabbits ; Reperfusion Injury ; diagnostic imaging ; Testicular Diseases ; diagnostic imaging ; Testis ; diagnostic imaging ; Ultrasonography

The effects of oxygen partial pressure on cryopreservation of the cells with organ preservation solution were explored. Hypoxic UW solution was made by purging the UW solution with argon. The pig proximal tubule epithelial cells (LLC-PK1 cells) were cryopreserved in hypoxic UW solution (Ar-UW group) or standard UW solution (UW group) at 4 degrees C for 48 h. Trypan blue staining and LDH detection were performed to evaluate the injury of the cells. The results showed that the oxygen partial pressure in Ar-UW group was significantly declined from 242+/-6 mmHg to 83+/-10 mmHg. After cryopreservation at 4 degrees C for 48 h, LDH leakage rate and Trypan blue-stained rate in Ar-UW group were (11.3+/-3.4)% and (10.5+/-4.7)%, respectively, which were significantly lower than in UW group [(49.5+/-6.9)% and (47.6+/-9.3)% respectively, both P<0.01]. It was concluded that lower oxygen partial pressure of UW solution was more beneficial to the cryopreservation of LLC.
Adenosine ; Allopurinol ; Cell Hypoxia ; Cell Line ; Cryopreservation ; Cryoprotective Agents ; Epithelial Cells/*cytology ; Glutathione ; Insulin ; Kidney Tubules, Proximal/cytology ; Organ Preservation Solutions ; Oxygen/pharmacology ; Raffinose ; Swine ; Tissue Preservation/methods

OBJECTIVETo investigate the protective effects of allopurinol (ALLO) on white matter damage in premature rats.

METHODSAn animal model for white matter damage was established by bilateral carotid artery occulation (BCAO). Eighty-four newborn SD rats (1 day old) were used in this study and were divided randomly into three groups [sham surgery (Sham); BCAO group (BCAO); allopurinol-treated group (ALLO)]. Pathological changes were studied 7 days and 14 days after BCAO, respectively. Myelin basic protein (MBP) was detected by immunohistochemistry 7 days and 14 days after BCAO, respectively. MBP-mRNA expression was determined 7 days and 14 days after BCAO respectively by reverse transcription-polymerase chain reaction (RT-PCR) with fluorescent quantitative method.

RESULTSIn BCAO group, mild or severe rarefaction was found in 10 cases in the corpus callosum area, especially at the cingulum. Pathological changes of white matter were found in 4 cases in internal capsule. Subcortex white matter rarefaction was found in 8 cases. The extent of white matter rarefaction in ALLO group was reduced significantly. Enlargement of bilateral ventricles was found in 6 of 8 cases in BCAO group. The average ventricle size in ALLO group (2.44 +/- 0.71)% was reduced significantly as compared with that in BCAO group (3.27 +/- 0.73)% (P < 0.05). Strong MBP positive staining was found in sub-cortex, corpus callosum, hippocampus gyrus, and internal capsule of P14 sham surgery group. In BCAO group the MBP staining extent was reduced. The extent of MBP staining of ALLO group was between the other two groups. The optical density (OD) of MBP positive staining in BCAO group (6.60 +/- 0.68) was found higher than that in sham surgery group (9.40 +/- 0.53), the difference was statistically significant (P < 0.05). Compared with BCAO group, OD value in ALLO group (7.10 +/- 0.18) increased significantly (P < 0.05). RT-PCR data showed that MBP-mRNA copies (log10) in P7 and P14 rats of both BCAO and ALLO groups were lower than that in sham surgery group (P < 0.01); However, MBP-mRNA copies in ALLO group were higher than that in BCAO group (P < 0.05).

CONCLUSIONSBCAO could be used in newborn rats (1 day old) to establish a premature white matter damage (WMD) animal model. Allopurinol may have a potential protective effect on premature SD rat with ischemic WMD.

Allopurinol ; pharmacology ; Animals ; Animals, Newborn ; Brain ; drug effects ; Brain Diseases ; metabolism ; pathology ; prevention & control ; Disease Models, Animal ; Immunohistochemistry ; Myelin Basic Protein ; genetics ; metabolism ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the antioxidant activity of methanolic extracts of Lantana camara (L. camara) various parts and the determination of their total phenolics content.

METHODSThe extract was screened for possible antioxidant activities by free radical scavenging activity(DPPH), xanthine oxidase inhibition activity and Griess-Ilosvay method.

RESULTSThe results showed that all the plant parts possessed antioxidant properties including radical scavenging, xanthine oxidase inhibition and nitrites scavenging activities. The antioxidative activities were correlated with the total phenol. The leaves extract of L. camara was more effective than that of other parts.

CONCLUSIONSThis study suggests that L. camara extracts exhibit great potential for antioxidant activity and may be useful for their nutritional and medicinal functions.

Allopurinol ; pharmacology ; Antioxidants ; pharmacology ; Chronic Disease ; drug therapy ; Free Radical Scavengers ; pharmacology ; Humans ; Lantana ; chemistry ; Methanol ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Phenols ; pharmacology ; Phytotherapy ; methods ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Reactive Oxygen Species ; Solvents

BACKGROUNDThe University of Wisconsin colloid based preserving solution (UW solution) is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng Organ Preserving Solution (CZ-1 solution) and compared it with UW solution.

METHODSA series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers, hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied.

RESULTSThere was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors' testicles. In some aspects, such as preserving rabbits' hearts, rats' intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22 - 31 hours were transplanted successfully and the mean renal function recovery time was (3.83 +/- 1.68) days.

CONCLUSIONSCZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China.

Adenosine ; pharmacology ; Allopurinol ; pharmacology ; Animals ; China ; Glutathione ; pharmacology ; Heart ; drug effects ; physiology ; Heart Transplantation ; methods ; Insulin ; pharmacology ; Intestine, Small ; drug effects ; physiology ; Kidney ; drug effects ; physiology ; Kidney Transplantation ; methods ; Liver ; drug effects ; physiology ; Liver Transplantation ; methods ; Lung ; drug effects ; physiology ; Lung Transplantation ; methods ; Male ; Organ Preservation ; economics ; methods ; Organ Preservation Solutions ; pharmacology ; Pancreas ; drug effects ; physiology ; Pancreas Transplantation ; methods ; Pharmaceutical Solutions ; pharmacology ; Rabbits ; Raffinose ; pharmacology ; Testis ; drug effects ; physiology

This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3'-carboxy-4'-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M1). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M1. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b5 reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.
Adenosine Monophosphate ; pharmacology ; Allopurinol ; pharmacology ; Aniline Compounds ; metabolism ; Animals ; Cimetidine ; pharmacology ; Coumarins ; metabolism ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P450 Family 2 ; Cytochrome-B(5) Reductase ; antagonists & inhibitors ; Cytosol ; metabolism ; Dicumarol ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Female ; Humans ; Liver ; cytology ; metabolism ; Male ; Microsomes, Liver ; metabolism ; Mitochondria, Liver ; metabolism ; NAD(P)H Dehydrogenase (Quinone) ; antagonists & inhibitors ; Propylthiouracil ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Steroid 21-Hydroxylase ; antagonists & inhibitors ; Xanthine Oxidase ; antagonists & inhibitors

In this study, SD rats were orally administrated with oteracil potassium (300 mg . kg-1 . d-1 ) to prepare the hyperuricemia model, and divided into normal, model, Allopurinol, LE high dosage, middle dosage and low dose (200, 100, 50 mg . kg-1 . d-1) groups. The rats were orally administrated with test drugs 1 hour later after being orally administrated with Oteracil potassium. After 7 days, serum uric acid, serum creatinine, uric acid and expression of relevant transporters in kidney were tested to study the regulatory effect of leonurus extracts on serum uric acid, renal function and relevant transporters in kidney of rats with hyperuricemia. Compared with the model group, the leonurus extract group could significantly down-regulate serum uric acid and creatinine levels of rats with hyperuricemia, and increase the urine uric acid level. Meanwhile, leonurus extracts could notably down-regulate the mRNA expressions of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), up-regulate the mRNA expressions of organic cation transportanter (OCT) and Carnitine transporter (OCTN) and promote the excretion of uric acid of kidney.
Allopurinol ; pharmacology ; Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Disease Models, Animal ; Down-Regulation ; Gene Expression Regulation ; drug effects ; Hyperuricemia ; blood ; drug therapy ; Kidney ; drug effects ; Leonurus ; chemistry ; Male ; Organic Anion Transporters ; genetics ; Oxonic Acid ; administration & dosage ; Plant Extracts ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Up-Regulation ; Uric Acid ; blood

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.
Adult ; Aged ; *Alleles ; Allopurinol/adverse effects/*pharmacology ; Anticonvulsants/*adverse effects ; Asian Continental Ancestry Group/*genetics ; Carbamazepine/adverse effects/*pharmacology ; Case-Control Studies ; Drug-Related Side Effects and Adverse Reactions/*genetics/immunology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-B Antigens/*genetics ; Humans ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stevens-Johnson Syndrome/ethnology/etiology/*genetics ; Triazines/adverse effects/*pharmacology