Alloxan, action

Alloxan (1003) has been observed in the mucus associated with dysentery and it was the very first pyrimidine made synthetically when Brugnatelli oxidized uric acid in 1818. Alloxan has an interesting diabetogenic action which appears to be associated with removal of essential zinc from insulin by chelation. Such permanent diabetes may be induced in fish, dogs, cats, sheep, some birds, monkeys and other creatures, but not in man, owls or guinea-pigs certain pyrimidines related to alloxan show some such activity. 

Diabetogenic actions of alloxan ARDS (some forms) ... 

The insulin producing P cells of the pancreas are selectively destroyed by alloxan, which is reduced there to dialurate. Isolated pancreatic islets of mice were protected against the action of alloxan, by BESOD, by catalase, and by scavengers of OH radicals. A treatment of rat pancreatic islets with SOD, catalase or diethylenetriaminepenta-acetate attenuated the effect of alloxan, suggesting again a participation of OH radicals... 

Erosive Action of ACT 5 Propellant A98-L Erythric Acid of Brugnatelli. See Alloxan A134-R... 

We detected also that the antioxidative enzymes activity in the pancreas of rats which are susceptible to alloxan-induced diabetes is significantly lower than in pancreas cells of guinea pigs which are very resistant to diabetogenic action of alloxan (Figure 14). 

Thus polyhydroxylated triterpenes from E. japonica are very active as hypoglycemic agents. Noreen and Villar (38,39) proposed that the crude alcoholic extract of E. japonica and tormentic acid act by stimulating Langerhan s p cells which results in an increased insulin release because the crude extract and tormentic acid are inactive in alloxan-treated animals. The action mechanism of S and 7 seems to be analogous. Studies are in progress to delineate this mechanism more precisely. 

Murexide is obtained by action of ammonia on the mixture of alloxan and alloxantin, obtained by evaporating a solution of uric acid in strong nitric acid. 

In addition lipid peroxidation can result from action of active oxygen species. This leads to destruction of metabolically necessary lipid molecules and damage to the structural integrity of cellular membranes. Damage from oxidative stress can occur with excessive production of active oxygen species, inadequate protection against such species, or both. Examples of toxicity from active oxygen species include the pancreatic beta-cell destruction by alloxan, the neurotoxicity of 6-hydroxydopamine, the cardiotoxicity of the anthracy-cline antibiotics, and the pulmonary toxicity of the herbicide paraquat. 

SOD3 knockout mice are apparently healthy but are more sensitive to hyperoxic lung injury [168], to ischemia-reperfusion injury [169], and to the diabetogenic action of alloxan [170]. 

Alloxan A crystalline oxidation product, C4H4N2O5. A substance formed by the action of nitric acid on uric acid ... 

Yiolurlo add—C R IV.O —is produced, along with alloxan, by the action of nitric add upon hydtmJio add. It forms small, readily soluble, octahedral crystalsL It is a strong monobasio acid, wboM salts are briU-i latly colored. 

Iffurexide. This isthopurpurate of ammonia, and consists of iridescent crys-tus, which reflect a beautiful men color, but transmit an equally fine reddi -purple color. It is obtained from alloxan, a substance formed by the action of nitric acid on uric acid. 

Alloxantin—CaH,N,0,—is a diureid crystallizing in small, brilliant, very sparingly soluble prisms, produced by the action of reducing agents upon alloxan, whose action is less powerful than that required to convert alloxan into dialuric acid. 

I. Mechanism of toxicity. PNU is believed to antagonize the actions of nicotinamide and, in a manner similar to that of alloxan and streptozocin, injure pancreatic beta cells. The mechanisms of autonomic neuropathy and central nervous system effects are unknown. Adrenergic neurons acting on blood vessels but not the heart are affected. As a result, orthostatic hypotension associated with an intact reflex tachycardia is the usual picture. 

Alloxan apparently also acts by interacting with SH groups and lowering the blood glutathione, since its action is prevented by SH-containing compounds such as glutathione, cysteine, BAL (2,3-dimercaptopropanol) or thioglycolic acid administered immediately before or within a few minutes after injection of alloxan [82, 86, 87]. However, the actual mechanism by which alloxan acts is still rather poorly understood. 

Barbituric acid does not have the diabetogenic action of alloxan (5-... 

Gao, D., Q. Li, Z. Liu, et al. 2007b. Hypoglycemic effects and mechanisms of action of Cortex Lycii Radicis on alloxan-induced diabetic mice. Yakugaku Zasshi 127(10) 1715-1721. 

Stanely, P, M. Prince, and V.P. Menon. 2000. Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats. /. Ethnopharmacol. 70(1) 9-15. 

Whatever the true mode of action of alloxan in producing diabetes, it seems likely that it is due to its properties as an oxidant. Other oxidants might have much the same effect, as is suggested by the report (Patterson, 1949) that dehydroascorbic acid (DHA), in doses of 0.7 g./kg. body weight on three successive days, produced diabetes in rats. This could be prevented by the prior administration of cysteine, glutathione, or BAL (Patterson and Lazarow, 1950). Many other aspects of alloxan diabetes have been reviewed in an earlier volume of this series (Bailey, 1949). 

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