allopurinol and Weight-Loss

Hyperuricemia may be a major contributor to the development or progression of chronic kidney disease (CKD). Although there is no clear cutoff uric acid (UA) value associated to the risk for kidney damage, it appears to be an increased risk as UA rises. Lifestyle interventions such as exercise, weight reduction, low consumption of purine-rich meat, or avoiding high fructose intake are recommended for all hyperuricemic patients. Lowering urate drugs such as allopurinol or febuxostat may be an option as a renoprotective agent; yet, randomized clinical trials evaluating the safety and efficacy of these drugs are limited to a small number of single-center studies. Several ongoing clinical trials aim to evaluate the safety and efficacy of these drugs. As of today, there is insufficient evidence to recommend the widespread use of UA-lowering therapy to prevent or slow down the progression of CKD. The purpose of this review is to summarize the evidence and future perspectives about the treatment of hyperuricemia in the prevention and progression of CKD.

Topics: Allopurinol; Diet; Disease Progression; Exercise; Febuxostat; Gout Suppressants; Humans; Hyperuricemia; Life Style; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Weight Loss

The mechanisms by which weight loss decreases serum uric acid (SUA) levels are poorly known. We aimed to investigate the role played by xanthine oxidase (XOD), metabolic status, and low-grade inflammation in decreased SUA levels induced by weight loss in obese patients.. Data were from a series of consecutive patients with severe obesity involved in a bariatric surgery program. Measurements of body composition and biologic samples were obtained before surgery and 6 months after surgery.. Among the 154 patients (mean ± SD age 41.0 ± 12.3 years, body mass index [BMI] 47.8 ± 7.2 kg/m(2) , 81% female), the mean ± SD weight loss at 6 months was 31.3 ± 7.8 kg. Reduction in SUA levels was modest (-10%): 4.98 ± 1.21 mg/dl at 6 months versus 5.52 ± 1.33 mg/dl at baseline (P < 0.001). The decrease in SUA levels was greatest (-18%) in hyperuricemic patients (n = 48). In these patients, circulating XOD activity decreased with weight loss (P < 0.0001). Multiple linear regression analysis revealed decreased SUA levels associated with decreased triglyceride levels (P = 0.0001) and BMI (P = 0.02) but not XOD activity, adipokine levels (leptin and adiponectin), insulin resistance, or levels of inflammatory variables (interleukin 6, orosomucoid, fibrinogen, and high-sensitivity C-reactive protein).. In obese patients, weight loss was associated with a decrease in both SUA levels and XOD activity. Our findings suggest that reduced SUA levels are not mediated by decreased XOD activity or improved insulin resistance but could be partly due to a reduction in triglyceride levels.

Topics: Adult; Bariatric Surgery; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hyperuricemia; Longitudinal Studies; Male; Obesity; Prospective Studies; Uric Acid; Weight Loss; Xanthine Oxidase

Increased xanthine oxidase (XO) activity and uric acid levels are known to be associated with obesity and hypertension; however, it is not known if obesity is directly responsible for these associations in youth. This study investigated the effect of weight loss on XO activity, uric acid, and their relationship to blood pressure change in obese youth to provide greater insight on how obesity increases cardiovascular risk.. This was an ancillary study in which 16 adolescents (mean age 15 ± 2 years) received meal replacement therapy over a period of four weeks. Outcomes measured at baseline and after intervention included weight, blood pressure, XO activity, plasma uric acid, uric acid clearance, and creatinine clearance.. After the meal replacement intervention, participants experienced reductions in body weight (109.2 ± 16 kg vs. 105.2 ± 14 kg, p < 0.0001) and BMI (38.7 ± 4 kg vs. 37.4 ± 3 kg, p < 0.0001). Plasma XO activity was reduced by 9.8% (p = 0.016). Uric acid clearance was decreased by 39% (p = 0.006). SBP (systolic blood pressure) and plasma uric acid concentrations were reduced but did not achieve statistical significance (p = 0.34 and 0.38, respectively). DBP (diastolic blood pressure) was unchanged (p = 0.86). No significant relationships were found between changes in blood pressure and changes in either XO activity or plasma uric acid levels.. Weight loss led to decreases in uric acid production by lowering XO activity and decreases in uric acid clearance by reducing glomerular filtration (GF) and increasing reabsorption. Changes in XO activity and uric acid levels did not correlate with changes in blood pressure.

Topics: Adolescent; Blood Pressure; Caloric Restriction; Female; Humans; Hypertension; Male; Minnesota; Obesity, Morbid; Pediatric Obesity; Risk Factors; Uric Acid; Weight Loss; Xanthine Oxidase

Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats. These findings may have important implications for diet selection in obese patients with ischemic heart disease.

Topics: Adiponectin; Animals; Antioxidants; Catalase; Diet, Carbohydrate-Restricted; Diet, High-Fat; DNA Copy Number Variations; DNA, Mitochondrial; Glycogen; Insulin; Male; Mitochondrial Turnover; Myocardial Reperfusion Injury; Myocardium; NADPH Oxidase 4; NADPH Oxidases; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Tyrosine; Weight Loss; Xanthine Oxidase

Canine leishmaniosis (CL) has become one of the most frequently diagnosed travel associated infection in dogs in Switzerland and Germany. The aim of the study was to define recommendations for treatment with allopurinol and follow-up examinations of dogs with CL in a non endemic area. 31 dogs infected with Leishmania were treated with allopurinol (10 - 15 mg/kg twice daily, per os) and the effectiveness was examined. The diagnosis had been confirmed by the detection of specific anti-Leishmania antibodies and/or Leihmania-DNA. 22 dogs had clinical signs (skin lesions, lameness or lack of fitness) and 9 dogs were asymptomatic but showed abnormal laboratory parameters. Under treatment with allopurinol the symptoms disappeared within 1 - 5 months in 20 dogs.. Die canine Leishmaniose gehört heute in der Schweiz und in Deutschland zu einer der am häufigsten diagnostizierten Reiseerkrankungen beim Hund. Ziel der Studie war es, praktische Empfehlungen hinsichtlich Therapie mit Allopurinol und Verlaufskontrollen in einem nicht endemischen Gebiet zu erarbeiten. Anhand von 31 importierten und reisebegleitenden Hunden mit Leishmania-Infektionen wurde die Wirkung von Allopurinol (10 – 15 mg/kg 2x täglich, per os) bezüglich klinischer und labordiagnostischer Parameter beobachtet. Die Diagnose erfolgte mittels DNA- und/oder Antikörpernachweis. 22 Hunde zeigten klinische Zeichen (Hautveränderungen, Lahmheiten und Konditionsstörungen) und 9 Hunde waren asymptomatisch, zeigten aber labordiagnostische Veränderungen. Unter Therapie mit Allopurinol verschwand die Symptomatik bei 20 Hunden innerhalb 1 – 5 Monaten.. La leishmaniose canine est l'une des maladies «de voyage» les plus souvent diagnostiquées actuellement en Suisse et en Allemagne. Le but de la présente étude était d'élaborer des recommandations pratiques relatives au traitement à l'allopurinol et au suivi dans une zone non-endémique. On a observé, sur la base de 31 chiens souffrant de leishmaniose, importés et accompagnant des voyageurs, l'effet de l'allopurinol (10 – 15 mg/kg, 2x/jour per os), tant du point de vue clinique que de celui des paramètres de laboratoire. Le diagnostic avait été posé par la mise en évidence de l'ADN et/ou des anticorps. 22 chiens présentaient des signes cliniques (lésions cutanées, boiteries et baisse de condition) et 9 chiens étaient asymptomatiques mais montraient des modifications à l'analyse de laboratoire. Sous allopurinol, les symptômes ont disparu en 1 à 5 mois chez 20 chiens.. In Svizzera e in Germania, la leishmaniosi canina è la malattia da viaggio diagnosticata più di frequente nei cani. Lo scopo di questo studio è l'elaborazione di raccomandazioni pratiche che riguardano la terapia con allopurinolo e i monitoraggi in una zona non endemica. Sulla base di 31 cani, importati o compagni di viaggio affetti da leishmaniosi, è stato osservato l'effetto di allopurinolo (10 – 15 mg/kg 2x al giorno, per os) riguardo i parametri di diagnostica clinici e di laboratorio. La diagnosi è stata effettuata via DNA e/o rilevazioni di anticorpi. I risultati hanno rivelato in 22 cani segni clinici (lesioni cutanee, zoppia e disturbi fisiologici) e in 9 cani nessun sintomo salvo dei cambiamenti diagnostici di laboratorio. Sotto trattamento con allopurinolo, i sintomi sono scomparsi in 20 cani entro 1 a 5 mesi.

Topics: Allopurinol; Animals; Antibodies, Protozoan; Antimetabolites; Antiprotozoal Agents; Dog Diseases; Dogs; Female; Lameness, Animal; Leishmania; Leishmaniasis; Male; Skin; Travel; Weight Loss

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P<0.05). EPA (18.2±3.2 pg/ml) and combination (18.4±3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05). Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml) compared to control (27.0±1.3 U/ml, P<0.01), GPx activity was lower in the EPA group (8.76±2.0 U/ml) compared to control (14.0±1.9 U/ml, P<0.05), and catalase activity was lower in the combination group (14.4±2.8 U/ml) compared to control (20.9±2.0 U/ml, P<0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.

Topics: Adenocarcinoma; Animals; Cachexia; Catalase; Cell Line, Tumor; Drug Evaluation, Preclinical; Drug Therapy, Combination; Eicosapentaenoic Acid; Enzyme Inhibitors; Female; Gene Expression; Mice; Mice, Inbred BALB C; Mice, Nude; Muscle, Skeletal; Muscular Atrophy; Neoplasm Transplantation; Neoplasms, Experimental; Organ Size; Oxidative Stress; Oxypurinol; Superoxide Dismutase; Tumor Burden; Weight Loss; Xanthine Oxidase

Topics: Allopurinol; Body Mass Index; Combined Modality Therapy; Gout; Humans; Life Style; Male; Middle Aged; Risk Factors; Secondary Prevention; Uricosuric Agents; Weight Loss

Cadmium (Cd) exposure has been recognized to result in a wide variety of cellular responses, including oxidative stress and body weight loss. The aim of the present study was to examine the effect of lycopene supplementation on the antioxidant defense system, lipid peroxidation (LPO) level, nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) production, and body weight in Cd-exposed rats. Animals were divided into four groups (n = 7): control, Cd-treated, Cd plus lycopene-treated, and lycopene-treated. Cadmium (as CdCl2) was administrated orally for 20 days (6.6 mg kg(-1) day(-1)), and lycopene (10 mg kg(-1) day(-1)) was similarly administered. Lycopene administration significantly suppressed Cd-induced LPO in plasma and kidney homogenates. Lycopene also reversed Cd-decreased body weight compared to the control. Cadmium treatment had diverse effects on the antioxidant enzyme activities. Although antioxidant superoxide dismutase activity was unchanged, glutathione peroxidase activity was decreased, and catalase activity was elevated in kidney homogenates of Cd-administrated group. However, lycopene treatment reversed Cd-changed enzyme activities to the control level. Xanthine oxidase activity and TNF-alpha concentration were not altered by Cd administration, indicating that superoxide anion production and inflammation were not stimulated. Cadmium did not change NO levels in kidney homogenates but decreased those in plasma, and this effect was not prevented by lycopene supplementation. The result suggests that consumption of adequate levels of lycopene may be useful to prevent heavy-metal-induced LPO and body weight loss.

Topics: Administration, Oral; Animals; Antioxidants; Body Weight; Cadmium; Carotenoids; Catalase; Kidney; Lipid Peroxidation; Lycopene; Male; Nitric Oxide; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Weight Loss; Xanthine Oxidase