Hypoxanthine and Xanthine as Markers in Early Diagnosis of Foetal Diseases

Gizzi, F.; Papponetti, Marco; Palka, Giandomenico; Ruffini, I.; Ilio, Carmine Di; O’Dorisio, M. Sue; Spoto, Giuseppe

doi:10.1007/978-1-4615-5381-6_148

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Elevated levels of purine metabolites in biofluids are reliable indicators of inflammation and tissue damage (15–17). Therefore, monitoring changes of these purinogenic compounds in WF could provide valuable information regarding the healing status of these wounds.…”

Section: Resultsmentioning

confidence: 99%

“…The final reactions in this pathway are the conversion by xanthine oxidase (XO) of hypoxanthine to xanthine, and subsequently xanthine to uric acid (UA), while simultaneously releasing the toxic superoxide radical (Figure 1). These metabolites have been extensively investigated in many disease states (14–17) with elevated levels of hypoxanthine and xanthine in cerebrospinal fluid and serum regarded as reliable early indicators of inflammatory and ischaemic tissue damage (15–17). However, no comprehensive profiling of these small heterocyclic metabolites has been reported for chronic wounds.…”

Section: Introductionmentioning

confidence: 99%

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Elevated uric acid correlates with wound severity

Fernandez

Upton

Edwards

et al. 2011

International Wound Journal

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Chronic venous leg ulcers are a major health issue and represent an often overlooked area of biomedical research. Nevertheless, it is becoming increasingly evident that new approaches to enhance healing outcomes may arise through better understanding the processes involved in the formation of chronic wounds. We have for the first time shown that the terminal purine catabolite uric acid (UA) is elevated in wound fluid (WF) from chronic venous leg ulcers with relative concentrations correlating with wound chronicity. We have also shown a corresponding depletion in UA precursors, including adenosine, with increased wound severity. Further, we have shown that xanthine oxidase, the only enzyme in humans that catalyses the production of UA in conjunction with a burst of free radicals, is active in chronic WF. Taken together, this provides compelling evidence that xanthine oxidase may play a critical role in the formation of chronic wounds by prolonging the inflammatory process.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Elevated uric acid correlates with wound severity

Fernandez

Upton

Edwards

et al. 2011

International Wound Journal

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“…Very limited information is available on the pharmacological effects or pathophysiological significance of hypoxanthine, the purine base that is cleaved off from inosine. Elevation of hypoxanthine levels in plasma, cerebrospinal fluid, and urine reflects the severity of tissue injury so well that determination of hypoxanthine in body fluids has been proposed to be a good clinical marker of ischemic and inflammatory diseases (25)(26)(27)(28)(29)(30). Hypoxanthine may have a dual role in ischemia and inflammation (31): it may promote tissue injury by serving as substrate for the xanthine oxidase-mediated generation of superoxide radical and thus contribute to tissue injury (32)(33)(34)(35)(36) and may also contribute to cell recovery after tissue injury by being used for the regeneration of ATP (31).…”

mentioning

confidence: 99%

Purines inhibit poly(ADP‐ribose) polymerase activation and modulate oxidant‐induced cell death

2001

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Purines such as adenosine, inosine, and hypoxanthine are known to have potent antiinflammatory effects. These effects generally are believed to be mediated by cell surface adenosine receptors. Here we provide evidence that purines protect against oxidant-induced cell injury by inhibiting the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Upon binding to broken DNA, PARP cleaves NAD+ into nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor proteins such as histones and PARP itself. Overactivation of PARP depletes cellular NAD+ and ATP stores and causes necrotic cell death. We have identified some purines (hypoxanthine, inosine, and adenosine) as potential endogenous PARP inhibitors. We have found that purines (hypoxanthine > inosine > adenosine) dose-dependently inhibited PARP activation in peroxynitrite-treated macrophages and also inhibited the activity of the purified PARP enzyme. Consistently with their PARP inhibitory effects, the purines also protected interferon gamma + endotoxin (IFN/LPS) -stimulated RAW macrophages from the inhibition of mitochondrial respiration and inhibited nitrite production from IFN/LPS-stimulated macrophages. We have selected hypoxanthine as the most potent cytoprotective agent and PARP inhibitor among the three purine compounds, and investigated the mechanism of its cytoprotective effect. We have found that hypoxanthine protects thymocytes from death induced by the cytotoxic oxidant peroxynitrite. In line with the PARP inhibitory effect of purines, hypoxanthine has prevented necrotic cell death while increasing caspase activity and DNA fragmentation. As previously shown with other PARP inhibitors, hypoxanthine acted proximal to mitochondrial alterations as hypoxanthine inhibited the peroxynitrite-induced mitochondrial depolarization and secondary superoxide production. Our data imply that purines may serve as endogenous PARP inhibitors. We propose that, by affecting PARP activation, purines may modulate the pattern of cell death during shock, inflammation, and reperfusion injury.

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Cyanidin-3-O-glucoside impacts fecal discharge of polystyrene microplastics in mice: Potential role of microbiota-derived metabolites

Chen

Xiang

et al. 2022

Toxicology and Applied Pharmacology

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Hypoxanthine and Xanthine as Markers in Early Diagnosis of Foetal Diseases

Cited by 4 publications

References 11 publications

Elevated uric acid correlates with wound severity

Elevated uric acid correlates with wound severity

Purines inhibit poly(ADP‐ribose) polymerase activation and modulate oxidant‐induced cell death

Cyanidin-3-O-glucoside impacts fecal discharge of polystyrene microplastics in mice: Potential role of microbiota-derived metabolites

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