Significance and Amplification Methods of the Purine Salvage Pathway in Human Brain Cells.

Previous studies suggest that uric acid or reactive oxygen species, products of xanthine oxidoreductase (XOR), may associate with neurodegenerative diseases. However, neither relationship has ever been firmly established. Here, we analyzed human brain samples, obtained under protocols approved by research ethics committees, and found no expression of XOR and only low levels of uric acid in various regions of the brain. In the absence of XOR, hypoxanthine will be preserved and available for incorporation into the purine salvage pathway. To clarify the importance of salvage in the brain, we tested using human induced pluripotent stem cell-derived neuronal cells. Stable isotope analyses showed that the purine salvage pathway was more effective for ATP synthesis than purine de novo synthesis. Blood uric acid levels were related to the intracellular adenylate pool (ATP + ADP + AMP), and reduced levels of this pool result in lower uric acid levels. XOR inhibitors are related to extracellular hypoxanthine levels available for uptake into the purine salvage pathway by inhibiting the oxidation of hypoxanthine to xanthine and uric acid in various organs where XOR is present and can prevent further decreases in the intracellular adenylate pool under stress. Furthermore, adding precursors of the pentose phosphate pathway enhanced hypoxanthine uptake, indicating that purine salvage is activated by PRPP replenishment. These findings resolve previous contradictions regarding XOR products and provide new insights into clinical studies. It is suggested that therapeutic strategies maximizing maintenance of intracellular adenylate levels may effectively treat pathological conditions associated with ischemia and energy depletion.

Allopurinol and oxypurinol differ in their strength and mechanisms of inhibition of xanthine oxidoreductase.

Xanthine oxidoreductase is a metalloenzyme that catalyzes the final steps in purine metabolism by converting hypoxanthine to xanthine and then uric acid. Allopurinol, an analog of hypoxanthine, is widely used as an antigout drug, as xanthine oxidoreductase-mediated metabolism of allopurinol to oxypurinol leads to oxypurinol rotation in the enzyme active site and reduction of the molybdenum Mo(VI) active center to Mo(IV), inhibiting subsequent urate production. However, when oxypurinol is administered directly to a mouse model of hyperuricemia, it yields a weaker urate-lowering effect than allopurinol. To better understand its mechanism of inhibition and inform patient dosing strategies, we performed kinetic and structural analyses of the inhibitory activity of oxypurinol. Our results demonstrated that oxypurinol was less effective than allopurinol both in vivo and in vitro. We show that upon reoxidation to Mo(VI), oxypurinol binding is greatly weakened, and reduction by xanthine, hypoxanthine, or allopurinol is required for reformation of the inhibitor-enzyme complex. In addition, we show oxypurinol only weakly inhibits the conversion of hypoxanthine to xanthine and is therefore unlikely to affect the feedback inhibition of de novo purine synthesis. Furthermore, we observed weak allosteric inhibition of purine nucleoside phosphorylase by oxypurinol which has potentially adverse effects for patients. Considering these results, we propose the single-dose method currently used to treat hyperuricemia can result in unnecessarily high levels of allopurinol. While the short half-life of allopurinol in blood suggests that oxypurinol is responsible for enzyme inhibition, we anticipate multiple, smaller doses of allopurinol would reduce the total allopurinol patient load.

Free Jejunal Graft Interposition with Vascular Reconstruction in Patients Undergoing Pharyngo Laryngo Esophagectomy.

BACKGROUND: Pharyngo-esophageal reconstruction using free jejunal grafts has been widely used for the treatment of locally advanced carcinomas of the hypopharynx and cervical esophagus. However, the procedure is technically demanding and requires complex recontractions. The aim of this study was to evaluate our institutional outcomes of reconstruction using a free jejunal graft with vascular reconstruction in patients undergoing pharyngo laryngo esophagectomy with a multidisciplinary surgical team. METHODS: There were 90 consecutive patients between October 2006 and February 2021. The mean age was 64.6 ± 10.3 years, and there were 76 male patients. Of 90 patients, 49 underwent preoperative chemotherapy and/or radiotherapy. Jejunal vessels were commonly anastomosed to the common carotid artery and the internal jugular vein (77.8% and 92.2%, respectively). Continuous intravenous infusion of heparin was used postoperatively. RESULTS: Necrosis of the graft was observed in 5 patients. An isolated revision of vein was necessary in 1 patient. In all cases of graft failure, heparin was not used postoperatively. On the other hand, among the patients without graft failure, heparin was used for about two-thirds of the patients and was significantly different (0% vs. 66%, P = 0.01). CONCLUSIONS: Free jejunal graft with vessel reconstruction is a safe and effective method for patients undergoing pharyngo laryngo esophagectomy. The position for the prevention of kinking as well anastomosis maneuver of vein is especially important. Moreover, early postoperative anticoagulation is essential.

Use of two parallel oxygenators during veno-venous extracorporeal membrane oxygenation in a patient with severe obesity and COVID-19 pneumonia.

Background: Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is one effective treatment for COVID-19 pneumonia, but controversy regarding VV-ECMO management in obese patients still exists. In this report, we described a case in which two oxygenators were used in parallel in a severely obese patient (Body mass index: 60 kg/m2, body surface area: 2.8 m2).Case: The case was of a 27-year-old man diagnosed with COVID-19 pneumonia and admitted to our hospital. VV-ECMO was required on the fifth day after admission due to gradually worsening respiratory conditions and partial pressure of arterial oxygen (PaO2)/FiO2 ratio of 77. Immediately after the initiation of VV-ECMO, post-oxygenator in circuit, PaO2 was low at 134 mmHg. Even though the VV-ECMO circuit was replaced on the same day, the PaO2 still was low at 261 mmHg. Thus, we decided to use two oxygenators in parallel, after which the PaO2 stabilized at 400-500 mmHg.Conclusions: In this case, VV-ECMO oxygenation could be stabilized by utilizing two oxygenators in parallel. Using two membrane oxygenators may be a treatment option in severely obese patients with respiratory failure.

Sepsis-Associated Muscle Wasting: A Comprehensive Review from Bench to Bedside.

Sepsis-associated muscle wasting (SAMW) is characterized by decreased muscle mass, reduced muscle fiber size, and decreased muscle strength, resulting in persistent physical disability accompanied by sepsis. Systemic inflammatory cytokines are the main cause of SAMW, which occurs in 40-70% of patients with sepsis. The pathways associated with the ubiquitin-proteasome and autophagy systems are particularly activated in the muscle tissues during sepsis and may lead to muscle wasting. Additionally, expression of muscle atrophy-related genes Atrogin-1 and MuRF-1 are seemingly increased via the ubiquitin-proteasome pathway. In clinical settings, electrical muscular stimulation, physiotherapy, early mobilization, and nutritional support are used for patients with sepsis to prevent or treat SAMW. However, there are no pharmacological treatments for SAMW, and the underlying mechanisms are still unknown. Therefore, research is urgently required in this field.

Reproductive Ability of Hybrids between Japanese Pond Turtle (Mauremys japonica) and Reeves' Pond Turtle (Mauremys reevesii).

Hybridization induced by human activities, such as crossbreeding between invasive and native species, can adversely affect the natural biodiversity of an ecosystem. In Japan, the endemic turtle species Mauremys japonica is known to hybridize with the alien species Mauremys reevesii, and putative hybrids have been encountered in the wild. If M. japonica × M. reevesii hybrids can readily crossbreed with M. japonica, the hybridization with M. reevesii could lead to the extinction of pure M. japonica populations. However, information on the reproductive ability of M. japonica × M. reevesii hybrids is limited. In this study, we collected wild-caught hybrids from across western Japan to assess their reproductive ability. We investigated the nesting season timing, clutch size, embryonic development, hatching success, and sperm viability. The results showed that female hybrids nested during the same months as the parental species and had similar clutch sizes and hatching success. No embryonic development abnormalities were detected, and viable sperm were observed in all hybrid male semen samples. In conclusion, the fertility of M. japonica × M. reevesii hybrids appears to be similar to the fertilities of the parental species, posing a potential challenge for M. japonica conservation.

Association of intensive care unit or paediatric intensive care unit admissions with the method of transporting patients: a multicentre retrospective study.

BACKGROUND: Reports regarding transportation methods of severely critical patients admitted to an intensive care unit (ICU) or paediatric ICU (PICU) are limited. In an attempt to address this research gap, this study aimed to test the hypothesis that prognosis is worse in patients transported by family members. METHODS: This multicentre study collected data from the Japanese Registry of Paediatric Acute Care database. Data concerning patients aged ≤16 years admitted to a participating hospital ICU or PICU and their transportation method to the hospital were extracted and divided into two groups: transported by family and transported by emergency medical services (EMS). RESULTS: Of the 2963 patients who met the criteria, 871 (29.4%) were transported by family and 2092 (70.6%) were transported by EMS. Significantly more patients with chronic conditions (551 patients, 63.3% vs. 845 patients, 40.4%; p <  0.01) or respiratory failure (414 patients, 47.5% vs. 455 patients, 21.7%; p <  0.01) were admitted to the ICU or PICU in the family transport group. There was no significant difference in survival rate between EMS and family transport group, matched by PIM2, chronic condition status and transport distance (OR:1.17, 95%CI:0.39-3.47, p = 0.78). CONCLUSION: The results of this study show that the transportation method does not affect the survival rate of paediatric patients. The proportion of patients with chronic conditions or those admitted because of respiratory failure was higher in the family transport group than in the EMS group. Therefore, as these patients are more likely to be admitted to the ICU or PICU, it is important to provide prompt respiratory care and medical interventions to achieve the best outcomes.

Relationship between preoperative anxiety and onset of delirium after cardiovascular surgery in elderly patients: focus on personality and coping process.

BACKGROUND: Postoperative delirium is associated with increased mortality. Therefore, it is important to manage delirium during the entire perioperative period. Preoperative anxiety is associated with poor prognosis in postoperative patients who have undergone cardiovascular surgery. This study aims to investigate the relationship between preoperative anxiety and onset of delirium after cardiovascular surgery in elderly patients (aged 65 years or older), considering the individual psychological characteristics, such as personality and stress coping skills in response to anxiety, as confounding factors. METHODS: This prospective study included patients aged >65 years in a preoperative state before undergoing cardiovascular surgery. Subjects were divided into two groups based on whether they experienced postoperative delirium, or not. We compared clinical and demographic factors, preoperative psychiatric and psychological factors, and intraoperative and perioperative physical factors between the control and delirium groups. Multiple imputations were used to account for missing data. RESULTS: Out of 168 subjects enrolled in this study, 26 (15.5%) developed postoperative delirium. Univariate analysis showed significant differences in age (P = 0.027), cognitive function (P = 0.007), agreeableness (P = 0.029), and the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score (P = 0.023) between the delirium and control groups. Multiple logistic regression analysis did not identify a significant association between preoperative anxiety and the onset of postoperative delirium. However, age (odds ratio (OR) = 1.114, P = 0.018), agreeableness (OR = 0.555, P = 0.008), and the APACHE-II score (OR = 1.227, P = 0.008) were identified as risk factors for postoperative delirium. CONCLUSION: Agreeableness, one of the personality traits associated with preoperative anxiety, appears to be involved in the development of postoperative delirium as an independent psychological factor, regardless of age or physical factors.

[Coronary Artery Bypass Grafting via Partial Sternotomy Late after Partial Chest Wall Resection:Report of a Case].

A 74-year-old man was referred to our department to receive coronary artery bypass grafting (CABG) because of severe triple vessel disease. He had undergone a chest wall resection including the right clavicle and the first and second ribs for the fibrosarcoma 40 years ago. The right internal thoracic artery was resected at the operation. Twenty-nine years after the operation, the plate used for the reconstruction of the chest wall was removed because of its infection. Off-pump CABG using left internal thoracic artery and vein grafts with lower partial sternotomy was successfully performed for the complete revascularization. This patient had a high possibility of sternum dehiscence and postoperative mediastinitis due to poor blood flow in the right upper sternum.

[Concurrent Surgical Venous Repair during Laser-assisted Pacemaker Lead Extraction].

Pacemakers are widely used to treat arrhythmia, however, one of problems after implantation of pacemaker is device infection. Total removal of leads and generator is recommended for radical cure. Recently, transvenous laser-assisted extraction of pacemaker leads has been developed and has achieved good results. However, catastrophic complications during pacemaker and implantable cardioverter-defibrillator leads extraction have been reported, and cases requiring surgical reconstruction have been also reported. Most of the repair technique include a direct suturing or a partial repair with patch. We herein report two cases of superior vena cava and innominate vein reconstruction with bovine pericardium during transvenous laser-assisted extraction. A hybrid approach using transvenous laser-assisted extraction and surgical repair through median sternotomy should be considered to perform complete lead extraction in complex cases with pacemaker lead infection.

Novel biomarkers of oxidative stress as predictive indicators of neurological outcome after out-of-hospital cardiopulmonary arrest.

AIM: Among patients of out-of-hospital cardiopulmonary arrest (OHCPA), only 6% resume their pre-OHCPA social life. The prediction of neurological outcome immediately after the return of spontaneous circulation (ROSC) is urgently needed in OHCPA patients. Novel biomarkers, biological antioxidant potential (BAP), and diacron-reactive oxygen metabolites (d-ROM) are potential predictors of neurological outcome after OHCPA. This study was conducted to evaluate the utility of BAP and d-ROM in the prediction of patient outcomes after OHCPA. METHODS: Blood samples were collected immediately after OHCPA patients were admitted to our hospital between May 2011 and June 2013. BAP and d-ROM concentrations were measured with the simple equipment FRAS4 ™ (Wismerll, Italy). Their association with favorable (cerebral performance category [CPC], 1 and 2) and unfavorable (CPC 3-5) clinical outcomes was compared. BAP and d-ROM values from 23 normal healthy volunteers (HV) were used as controls. RESULTS: Overall, 152 OHCPA patients were included, and 26 patients achieved ROSC. Eleven died during hospitalization were allocated a CPC of 5 and remaining patients were discharged or transported (CPC 1: n = 4; CPC 2: n = 6; CPC 3: n = 3; CPC 4: n = 2; CPC 5: n = 11). The receiver operating characteristics curve of d-ROM and BAP for predicting survival 28 days after OHCPA was 0.596 and 0.834, respectively. Patients without ROSC had significantly higher BAP than HV and patients with ROSC (p < 0.001). A significant correlation was evident between BAP and the time to ROSC (r = 0.641, p < 0.01). CONCLUSION: Oxidative stress, indicated by BAP on admission, strongly correlated with the neurological outcome after OHCPA.

Rosmarinic Acid and Sodium Citrate Have a Synergistic Bacteriostatic Effect against Vibrio Species by Inhibiting Iron Uptake.

BACKGROUND: New strategies are needed to combat multidrug-resistant bacteria. The restriction of iron uptake by bacteria is a promising way to inhibit their growth. We aimed to suppress the growth of Vibrio bacterial species by inhibiting their ferric ion-binding protein (FbpA) using food components. METHODS: Twenty spices were selected for the screening of FbpA inhibitors. The candidate was applied to antibacterial tests, and the mechanism was further studied. RESULTS: An active compound, rosmarinic acid (RA), was screened out. RA binds competitively and more tightly than Fe3+ to VmFbpA, the FbpA from V. metschnikovii, with apparent KD values of 8 µM vs. 17 µM. Moreover, RA can inhibit the growth of V. metschnikovii to one-third of the control at 1000 µM. Interestingly, sodium citrate (SC) enhances the growth inhibition effect of RA, although SC only does not inhibit the growth. The combination of RA/SC completely inhibits the growth of not only V. metschnikovii at 100/100 µM but also the vibriosis-causative pathogens V. vulnificus and V. parahaemolyticus, at 100/100 and 1000/100 µM, respectively. However, RA/SC does not affect the growth of Escherichia coli. CONCLUSIONS: RA/SC is a potential bacteriostatic agent against Vibrio species while causing little damage to indigenous gastrointestinal bacteria.

Novel endoscopic marking clip equipped with resin-conjugated fluorescent indocyanine green during laparoscopic surgery for gastrointestinal cancer.

PURPOSE: Intraoperative identification of the cancer location is often difficult to conduct during laparoscopic surgery, especially in early-stage cancers. This study aimed to investigate the feasibility and accuracy of a novel endoscopic clip resin-conjugated fluorescent indocyanine green during laparoscopic surgery for gastrointestinal cancer. METHODS: Preoperative placement of endoscopic marking clips equipped with resin-conjugated fluorescent indocyanine green was performed to determine the resection margin in eight patients with gastrointestinal cancer. During laparoscopic surgery, a dedicated laparoscopic system with a xenon light source was used to detect fluorescence. The evaluation determined whether the fluorescent from the clips was visualized during laparoscopic surgery. RESULTS: Fluorescent signal emitted from ICG in the resin of the clips was detected in six patients from the outer layer of the serosal surfaces of the gastrointestinal tract, and the clips aided in accurate resection line of the organ. There were no significant differences of age, gender, and BMI between the patients in whom we could and could not detect ICG fluorescence. CONCLUSIONS: The results demonstrated the usefulness of a novel clip-equipped fluorescent resin, which is a promising diagnostic tool to detect accurate tumor location during laparoscopic surgery.

Characteristics of indoor injuries in hotels compared to home among young children.

BACKGROUND: Although attention has recently been afforded to home injury prevention for young children, we often encounter young children who have experienced indoor injuries at places other than the home. We aimed to identify characteristics of unintentional indoor injuries that occurred when young children were not at home. METHODS: We retrospectively reviewed the medical records of young children (aged <6 years) with indoor injuries from January to June 2017. We classified patients injured in hotel rooms as the "Hotel group" and compared them to patients injured at home ("Home group"). RESULTS: Among 102 patients who met the study criteria, 33 patients (32.4%) were classified as the Hotel group. Falls were the most frequent cause of injury in both groups (Home, 56.5% versus Hotel, 87.9%). Falls from beds were more likely to happen in hotel rooms (1.4% versus 48.5%). In regard to fall-associated injuries, head and / or facial injury was most frequent in both groups (Home, 92.3% versus Hotel, 89.7%). A suture and follow-up were less likely in the Home group than in the Hotel group (18.8% versus 42.4%, 39.1% versus 69.7%, respectively). CONCLUSIONS: In hotel rooms, head and / or facial injuries due to falling from a bed were the most common types of injury, and they often needed more invasive procedures than home injuries. Injuries that tended to occur in hotel rooms are more predictable than home injuries. Modification of the surrounding environment has the potential to prevent unintentional injuries not only in the home environment but also in hotel rooms.

Enlarged coronary sinus thrombosis after repair of Ebstein's anomaly.

A 58-year-old woman was referred to our hospital with progressively increasing breathlessness. She reported a history of bioprosthetic valve implantation for tricuspid valve replacement and direct closure of an atrial septal defect for Ebstein's anomaly, 31 years before presentation. Transthoracic echocardiography revealed prosthetic valve failure, an enlarged coronary sinus, and severe mitral regurgitation. Computed tomography revealed a giant coronary sinus with thrombosis and persistent left superior vena cava. She underwent successful mitral and tricuspid valve replacement; however, severe hemodynamic deterioration necessitated mechanical ventilatory support with extracorporeal membrane oxygenation.

Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method.

PURPOSE: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method. METHODS: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching. RESULTS: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings. CONCLUSION: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

[Cardiac and Aortic Surgery and Perioperative Management in Patients with Malignant Tumors].

Managing patients with concurrent malignant neoplasms and cardiovascular disease is an important issue, especially with aging populations;however, the optimal treatment strategy in these patients remains controversial. We report 27 patients with simultaneous cardiac and malignant disease in our institution over the past 12 years;23 patients underwent cardiovascular surgery, 4 patients underwent cardiovascular surgery after treatment for malignant disease, and 3 patients died of malignant disease. The treatment strategy for patients with concurrent cardiac and malignant disease should be chosen according to the severity of the cardiovascular disease and the expected prognosis of the malignant disease.

Understanding the Molecular Mechanism Underlying the High Catalytic Activity of p-Hydroxybenzoate Hydroxylase Mutants for Producing Gallic Acid.

p-Hydroxybenzoate hydroxylase (PHBH) is a flavoprotein monooxygenase that catalyzes the hydroxylation of p-hydroxybenzoate (p-OHB) to 3,4-dihydroxybenzoate (3,4-DOHB). PHBH can bind to other benzoate derivatives in addition to p-OHB; however, hydroxylation does not occur on 3,4-DOHB. Replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. In this study, we report how the L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3-fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wastes reduced nicotinamide adenine dinucleotide phosphate by producing H2O2. To further elucidate the molecular mechanism underlying this higher catalytic activity, we performed molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, in addition to determining the crystal structure of the Y385F·3,4-DOHB complex. The simulations showed that the Y385F mutation facilitates the deprotonation of the 4-hydroxy group of 3,4-DOHB, which is necessary for initiating hydroxylation. Moreover, the L199V mutation in addition to the Y385F mutation allows the OH moiety in the peroxide group of C-(4a)-flavin hydroperoxide to come into the proximity of the C5 atom of 3,4-DOHB. Overall, this study provides a consistent explanation for the change in the catalytic activity of PHBH caused by mutations, which will enable us to better design an enzyme with different activities.

Voiding behavior and chronic pelvic pain in two types of rat nonbacterial prostatitis models: Attenuation of chronic pelvic pain by repeated administration of tadalafil.

BACKGROUND: Experimental autoimmune prostatitis (EAP) and prostatitis induced by 17ß-estradiol treatment combined with castration (hormone/castration-induced prostatitis; HCP) are the most commonly used rodent models of nonbacterial prostatitis. We studied the effect of the phosphodiesterase 5 inhibitor tadalafil on chronic pelvic pain in two such models in rats. METHODS: EAP was induced by intradermal injection of rat prostate antigen and complete Freund's adjuvant on Days 0 and 28. HCP was induced by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. On Day 42 after antigen injection in the EAP model and Day 30 after castration in the HCP model, we investigated voiding behavior, pelvic pain (measured by applying von Frey filaments to the lower abdomen), and inflammatory changes, including changes in histopathology and IL-1ß, CCL2, and CCL3 mRNA levels. We investigated the effect of repeated administration of tadalafil on chronic pelvic pain in both models. RESULTS: In the EAP model, we observed inflammation in the ventral prostate, while in the HCP model, we observed inflammation in the lateral lobe of the prostate. Neither model showed any change in voiding behavior. As well as in the EAP model, in which chronic pelvic pain was observed, we found for the first time that HCP led to a significant increase in chronic pelvic pain. Repeated treatment with tadalafil attenuated the chronic pelvic pain in both models. CONCLUSIONS: Chronic pelvic pain was induced in both EAP and HCP models. Tadalafil significantly attenuated the chronic pelvic pain in both models.

Metabolomics analysis elucidates unique influences on purine / pyrimidine metabolism by xanthine oxidoreductase inhibitors in a rat model of renal ischemia-reperfusion injury.

BACKGROUND: Clinically applied as anti-gout drugs, xanthine oxidoreductase (XOR) inhibitors, especially the potent, selective, non-purine-analog XOR inhibitors febuxostat and topiroxostat, exert organ-protective effects. We tested the hypothesis that preservation of tissue concentrations of high-energy phosphates, such as ATP and ADP, contributes to organ-protective effects through CE-TOFMS metabolomics. METHODS: Rats were subjected to 30 min of renal ischemia-reperfusion (I/R) injury 60 min after oral administration of 10 mg/kg febuxostat, 10 mg/kg topiroxostat, 50 mg/kg allopurinol, or vehicle. RESULTS: In non-purine-analog XOR inhibitor-treated groups, renal concentrations of high-energy phosphates were greater before and after I/R injury, and renal adenine compounds were less depleted by I/R injury than in the vehicle and allopurinol groups. These findings were well in accordance with the proposed hypothesis that the recomposition of high-energy phosphates is promoted by non-purine-analog XOR inhibitors via the salvage pathway through blockade of hypoxanthine catabolism, whereas non-specific inhibitory effects of allopurinol on purine/pyrimidine enzymes impede this re-synthesis process. CONCLUSIONS: This metabolic approach shed light on the physiology of the organ-protective effects of XOR inhibitors.