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1.
Curr Pharm Des ; 24(20): 2250-2254, 2018.
Article in English | MEDLINE | ID: mdl-30039753

ABSTRACT

Chronic use of opiates for control of chronic pain is complicated by the development of tolerance and hyperalgesia, and hence usually entails dose escalation and diminished efficacy. Our evolving understanding of the mechanisms mediating induction of morphine tolerance may enable discovery of adjunct measures which can prevent this tolerance; this essay proposes that certain nutraceuticals may have utility in this regard. Considerable evidence now points to an obligate role for production of peroxynitrite and other oxidants in the dorsal horn in development of morphine tolerance. Various isoforms of NADPH oxidase are the chief source of the superoxide which gives rise to these oxidants. Since heme oxygenase, via its products bilirubin and carbon monoxide, functions as a physiological inhibitor of various isoforms of NADPH oxidase, phase 2-inducing nutraceuticals with blood brain-barrier permeability such as lipoic acid, an effective inducer of heme oxygenase-1, may have potential for prevention of morphine tolerance; indeed, this has been demonstrated in a mouse study. The phycocyanobilin (PhyCB) chromophore of spirulina, a structural analog of biliverdin, shares bilirubin's ability to inhibit NAPDH oxidase complexes; hence, administration of spirulina or of PhyCB-enriched spirulina extracts merits evaluation in rodent models of morphine tolerance. Uric acid quenches peroxynitrite-derived radicals, and its plasma level can be boosting via supplementation with inosine; indeed, administration of inosine has been shown to counteract development of hyperalgesia in rodents. If practical doses of these agents can be shown to prevent morphine tolerance and hyperalgesia in rodents, their use as adjuvants to clinical opiate therapy should be assessed.


Subject(s)
Dietary Supplements , Drug Tolerance , Opiate Alkaloids/pharmacology , Phycobilins/pharmacology , Phycocyanin/pharmacology , Humans , Opiate Alkaloids/adverse effects , Oxidants/metabolism , Phycobilins/administration & dosage , Phycocyanin/administration & dosage
2.
J Med Food ; 10(4): 566-70, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18158824

ABSTRACT

Recent research reveals that free bilirubin functions physiologically as a potent inhibitor of NADPH oxidase activity. The chromophore phycocyanobilin (PCB), found in blue-green algae and cyanobacteria such as Spirulina, also has been found to be a potent inhibitor of this enzyme complex, likely because in mammalian cells it is rapidly reduced to phycocyanorubin, a close homolog of bilirubin. In light of the protean roles of NADPH oxidase activation in pathology, it thus appears likely that PCB supplementation may have versatile potential in prevention and therapy -- particularly in light of rodent studies demonstrating that orally administered Spirulina or phycocyanin (the Spirulina holoprotein that contains PCB) can exert a wide range of anti-inflammatory effects. Until PCB-enriched Spirulina extracts or synthetically produced PCB are commercially available, the most feasible and least expensive way to administer PCB is by ingestion of whole Spirulina. A heaping tablespoon (about 15 g) of Spirulina can be expected to provide about 100 mg of PCB. By extrapolating from rodent studies, it can be concluded that an intake of 2 heaping tablespoons daily would be likely to have important antioxidant activity in humans -- assuming that humans and rodents digest and absorb Spirulina-bound PCB in a comparable manner. An intake of this magnitude can be clinically feasible if Spirulina is incorporated into "smoothies" featuring such ingredients as soy milk, fruit juices, and whole fruits. Such a regimen should be evaluated in clinical syndromes characterized and in part mediated by NADPH oxidase overactivity in affected tissues.


Subject(s)
Phycobilins/administration & dosage , Phycocyanin/administration & dosage , Spirulina/chemistry , Anti-Inflammatory Agents/administration & dosage , Diet , Enzyme Inhibitors/administration & dosage , Humans , NADPH Oxidases/antagonists & inhibitors , NADPH Oxidases/physiology
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