Behavioural reactions of random-bred mice under the influence of hypouricemia and Aegopodium podagraria L. preparations

Abstract

Aims: Aegopodium podagraria L. preparations normalize uric acid metabolism and exert organoprotective effects. Still, their efficacy was not determined in combined use with therapeutic doses of allopurinol. This study addressed the changes of uric acid metabolism and CNS in mice undergoing hyperuricemia correction with allopurinol combined with A. podagraria extract or tincture. Study Design: The mice were randomly distributed to five groups: Group I: intact control; Group II: control for manipulations and hypouricemia (allopurinol, 2.5 mg/kg); Group III: potassium oxonate (PO), 250 mg/kg + allopurinol, 10 mg/kg; Group IV: PO, 250 mg/kg + allopurinol, 10 mg/kg + extract, 1 g/kg; Group V: PO, 250 mg/kg + allopurinol, 10 mg/kg + tincture, 1 ml/kg. Place and Duration of Study: Central Scientific-Research Laboratory, National University of Pharmacy, Kharkiv, Department of Biochemistry, Kharkiv National Medical University, June 2017 – September 2017. Methodology: Beginning from the 15th day psychopharmacological tests were carried out. At day 21, xanthine oxidase activity in the liver and kidney, uricase activity in the liver, uric acid level in blood and brain, GABA, serotonin, aspartic and glutamic acids concentrations in the brain were determined. Results: The extract as well as the tincture did not counteract the influence of allopurinol on xanthine oxidase, liver uric acid level was decreased, and uricemia slightly elevated (especially by the tincture) allowing to suggest the changes of uric acid transport. Such changes were also possible in brain resulting in the increased uric acid level in animals receiving combinations with A. podagraria or allopurinol per se. In these groups, GABA brain content was reduced, while aspartic and glutamic acids content was increased. The extract and especially the tincture decreased brain serotonin level (which was elevated by PO and allopurinol). Allopurinol per se and its combinations with A. podagraria preparations mildly reduced locomotor activity. Allopurinol and PO increased the duration of stay in the open arms of the elevated plus maze that was eliminated by the tincture, which also normalized the number of mice immediately visiting the open arm. The extract and the tincture decreased depressivity level in the tail suspension test. The tincture restored physical endurance in the weight-loading forced swimming test. Conclusion: The results substantiate the combined use of allopurinol and A. podagraria preparations, which do not counteract the main effect of allopurinol and do not cause the negative changes of the CNS (no unfavourable shifts in locomotion and anxiety are induced, while depressivity and physical endurance are partially improved). Further studies are needed to elucidate the mechanisms of A. podagraria active components interaction with allopurinol within the brain.