Treatment of hypertension complicated with hyperuricemia / 中国临床药理学与治疗学

Hypertension and hyperuricemia often coexist, and have a high incidence and often incur great harm. The current guidelines recommend active control of uric acid and blood pressure levels. But patients with high uric acid and high blood pressure still need detailed guidelines to standardize the treatment to avoid incurring more drug-related side effects. This article reviews the epidemiology and clinical harm, the therapeutic target value, the consensus and controversy on therapeutic treatment of high blood pressure combined with high uric acid.

Analgesic activity of allopurinol and febuxostat in experimental animals

Background: Currently, two classes of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics are used to manage pain in different clinical situations. Chronic uses of these drugs have various adverse effects like gastric ulceration/bleeding, analgesic nephropathy and respiratory depression, physical dependence, addiction, respectively. Xanthine oxidase inhibitors, used for chronic gout, might have a role in alleviation of pain, as per literature survey. Hence, the present study was carried out to evaluate the potential analgesic activity of allopurinol and febuxostat in different experimental models.Methods: The analgesic activity of allopurinol and febuxostat was assessed by employing two different experimental pain models-tail flick latency model in rats for central analgesia and acetic acid induced writhing model in mice for peripheral analgesia and was compared with tramadol and aspirin.Results: Allopurinol and febuxostat produced significant central and peripheral analgesic effects as is evident from increase in reaction time in tail flick test and inhibition in number of writhes in acetic acid induced writhing test.Conclusions: The results of the present study demonstrate marked analgesic effect of allopurinol and febuxostat.

Research progress of puerarin and its derivatives on anti-inflammatory and anti-gout activities / 中国中药杂志

The research progress of puerarin and its derivatives in anti-inflammatory and anti-gout activities was reviewed in this paper. Puerarin possesses anti-inflammatory activity by affecting immunocyte, inflammation cytokines and signaling pathway. Puerarin also has anti-gout activity through inhibition of xanthine oxidase, promoting the excretion of uric acid to reduce serum uric acid level. Although its ability in reducing uric acid level was lower than that of allopurinol in clinical application, puerarin can also enhance the total antioxidant and free radical scavenging with stronger anti-inflammatory effect, so it will be a promising research direction to find new drugs with better anti-gout activity and less side effects by modifying the chemical structure of puerarin.

Synthesis and xanthine oxidase inhibitory activities of 2-phenyl-tetrahydrothiopyrano［4, 3-d］ pyrimidine derivatives / 中国药科大学学报

@#Twelve novel 2-phenyl -tetrahydrothiopyrano［4, 3-d］pyrimidine derivatives were synthesized from 4-hydroxy-benzonitrile by etherification, hydrolysis, acylation and addition reactions, etc. The inhibitory activities against xanthine oxidase were evaluated in vitro. Results showed that compounds 8a-8h exhibited varying inhibitory potencies on xanthine oxidase at 100 μmol/L, significantly better than those of compounds 6a-6d, indicating that carboxy-substituted pyrimidine is beneficial to the inhibitory activity. Among compounds 8a-8h, 8f with isopropionic acid-substituted pyrimidine and ethyl-substituted phenol showed the best inhibition with IC50 of 76. 0 μmol/L.

Characterization of an Anti-gout Xanthine Oxidase Inhibitor from Pleurotus ostreatus

We selected Pleurotus ostreatus from among several edible mushrooms because it has high anti-gout xanthine oxidase (XOD) inhibitory activity. The maximal amount of XOD inhibitor was extracted when the Pleurotus ostreatus fruiting body was treated with distilled water at 40degrees C for 48 hr. The XOD inhibitor thus obtained was purified by Sephadex G-50 gel permeation chromatography, ultrafiltration, C18 solid phase extraction chromatography and reverse-phase high-performance liquid chromatography with 3% of solid yield, and its XOD inhibitory activity was 0.9 mg/mL of IC50. The purified XOD inhibitor was a tripeptide with the amino acid sequence phenylalanine-cysteine-histidine and a molecular weight of 441.3 Da. The XOD inhibitor-containing ultrafiltrates from Pleurotus ostreatus demonstrated dose-dependent anti-gout effects in a Sprague-Dawley rat model of potassium oxonate-induced gout, as shown by decreased serum urated levels at doses of 500 and 1,000 mg/kg, although the effect was not as great as that achieved with the commercial anti-gout agent, allopurinol when administered at a dose of 50 mg/kg.

Effect of Xanthine Oxidase Inhibitor on Cerebral Hypoxia-Ischemia in Neonatal Rats

PURPOSE: In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes. METHODS: Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day old neonatal rats which were subjected to unilateral common carotid artery occlusion and exposed to hypoxic condition for 3 hours. The protective effect of XO inhibitor was examined by the cell number, cell viability, LDH and PS on 14 days after H-I with allopurinol intraperitoneal injection 15 minutes prior to H-I. In addition, the effect of allopurinol on PKC activity in hypoxic conditions was examined in neurons. RESULTS: 72 hours from H-I, the cell numbers and viability were decreased significantly in time- dependent manner on neurons and those of astrocytes also decreased slightly, compared with control. In neonatal rats treated with H-I, the cell number, cell viability, and PS in neurons were decreased, but LDH was increased significantly compared with control. In neonatal rats pretreated with allopurinol, the cell number and viability, and PS in neurons were increased and LDH was decreased significantly compared with H-I. PKC was increased remarkably after hypoxic condition. But PKC was decreased significantly against hypoxic condition after allopurinol pretreatment. CONCLUSION: From these results, it is suggested that H-I is more toxic in neurons than astrocytes and allopurinol is very protective with increasing of PS, and decreasing of LDH and PKC in neurons from hypoxic-ischemic condition.

Reduction of Postischemic Cerebral Infarction and Cerebral Edema by Superoxide Dismutase and Allopurinol

The authors have inverstigated the hypothesis that ischemic injury could be attenuated by xanthine oxidase inhibitor(Allopurinol) and superoxide dismutase(SOD). This study used rat MAC model. Each animal was assigned to four groups which was composed with control group, allopurinol pretreated group(50mg/kg. I.P single). SOD pretreated group(16,000 I.U/kg I.V q 15min for 4hours) and combined pretreatment group. Oxygen derived free radicals have been implicated in various pathological conditions including ischemia. Xanthine oxidase serve as a source of oxidizing agents such as superoxide radical and hydrogen peroxide. The superoxide flux in normal cells appears to have necessitated the development of SOD, which scavenges the superoxide by dismutation. Infarcted area was measured by computerized morphometric analysis after triphenyl tetrazolium chloride staining, infarcted area was reduced in SOD treated group(p=0.005) and SOD, allopurinol combined group(P=0.035). Brain edema was measured by gravimetric method. And it was reduced in Allopurinol treated group(P=0.001) and SOD allopurinol combined group (P<0.001). Thus it was revealed that ischemic injury might be reduced by either decrease of production or increase of scavenger and the combination of two should be more efficious.