Effect of hypoxanthine, antioxidants and allopurinol on cholinesterase activities in rats

Abstract

In the present study, we investigate the in vitro effect of hypoxanthine on acetylcholinesterase and butyrylcholinesterase activities in the hippocampus, striatum, cerebral cortex and serum of 15-, 30- and 60-day-old rats. Furthermore, we also evaluated the influence of antioxidants, namely α-tocopherol (trolox) and ascorbic acid, and allopurinol to investigate the possible participation of free radicals and uric acid in the effects elicited by hypoxanthine on these parameters. Acetylcholinesterase and butyrylcholinesterase activities were determined according to Ellman et al. (Biochem Pharmacol 7:88-95, 1961), with some modifications. Hypoxanthine (10.0 μM), when added to the incubation medium, enhanced acetylcholinesterase activity in the hippocampus and striatum of 15- and 30-day-old rats and reduced butyrylcholinesterase activity in the serum of 60-day-old rats. The administration of allopurinol and/or antioxidants partially prevented the alterations caused by hypoxanthine in acetylcholinesterase and butyrylcholinesterase activities in the cerebrum and serum of rats. Data indicate that hypoxanthine alters cholinesterase activities, probably through free radicals and uric acid production since the alterations were prevented by the administration of allopurinol and antioxidants. It is presumed that the cholinesterase system may be associated, at least in part, with the neuronal dysfunction observed in patients affected by Lesch-Nyhan disease. In addition, although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins and allopurinol might serve as an adjuvant therapy to avoid progression of brain damage in patients affected by this disease.

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“…Previous studies suggest that purine metabolites might be involved in the pathophysiology of AD (Xiang et al, 2015), which was also proved in current models. In addition, hypoxanthine could enhance acetylcholinesterase activity in the hippocampus (Wamser et al, 2013), which decreases acetylcholine levels and is closely related to the pathophysiology of AD. Moreover, hypoxanthine has also been reported to induce oxidative stress in rat striatum, which is vital to the pathogenesis of AD and will impair brain memory of mice (Bavaresco et al, 2007).…”

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“…This could lead to the accumulation of hypoxanthine [31] . It was reported that hypoxanthine enhanced acetylcholinesterase (AChE) activity in the hippocampus and striatum of 15- and 30-d-old mice, when added to the incubation medium [32] . AChE is associated with the pathophysiology of AD.…”

Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy

“…Hypoxanthine is another purine compound that implicated in AD progression. Acetylcholinesterase is closely associated with AD pathophysiology and hypoxanthine could enhance acetylcholinesterase activity when it is added to incubation medium [39]. Constant stimulation of acetylcholinesterase activity might reduce acetylcholine levels, an essential neurotransmitter of central nervous system, and hypoxanthine therefore contributes much to memory deficits by acetylcholinesterase-related mechanism.…”