The effects of goutweed (Aegopodium podagraria L.) tincture on the background of toxic doses of allopurinol with the excessive intake of purine derivatives and proteins

Abstract

There is an increasing interest in the use of herbal preparations as part of the combined therapy, including cases of hyperuricemia and gout. Preparations of goutweed (Aegopodium podagraria L.) aerial part are characterized by organoprotective and favorable metabolic effects, including the effect on the uric acid metabolism largely related to hydroxycinnamic acids. Allopurinol continues to be the most widely used hypouricemic drug.
Aim. To characterize the renal, metabolic, and psychotropic effects of goutweed tincture combined with allopurinol in rats under the conditions of the excessive intake of purine derivatives and proteins.
Materials and methods. The experiments were performed on the background of the excessive intake of purine derivatives and proteins in rats (10-day administration of the yeast extract in the dose of 10 g/kg with addition of molybdenum in the amount of 0.3 mg per animal and i/p injection of inosine in the dose of 50 mg/150 g). Goutweed tincture (1 ml/kg), allopurinol (50 mg/kg) and their combination were administered intragastrically during the whole period of the studies. The state of the excretory renal function, biochemical parameters of the blood plasma, the activity of xanthine oxidase (CSR) and the content of uric acid in the liver and kidneys, as well as the state of the CNS in the combined open field and an elevated plus maze tests were studied.                  Results. The renal injury on the background of excessive purine derivatives and proteins was verified by the criteria of hyperfiltration with increased water reabsorption and reduced ability of the kidney to excrete water load, a decrease in urea clearance and an increase of proteinuria. The level of urea and nitrogen of amino groups of the low-molecular compounds in the blood plasma increased in the absence of changes in creatininemia and uricemia (with a marked increase of renal excretion of uric acid on the background of the liver xanthine oxidase increased activity). Under the conditions of the excessive intake of purine derivatives and proteins goutweed tincture provided effective excretion of potassium, normalized the total protein content in the blood, as well as urea clearance without affecting other parameters and not leading to toxic effects. It also did not change the uric acid content and the xanthine oxidase activity of the liver and kidneys. On the background of allopurinol, the severity of the kidney damage increased with the threefold increase in the relative kidney weight, hyperazotemia, an abrupt decrease in GFR and urea clearance, reabsorption decrease, a tendency to increase in natriemia and, especially kalemia, a significant increase of proteinuria, as well as an increase in the total protein content in the blood. Goutweed tincture did not enhance the toxicity of allopurinol and did not prevent xanthine oxidase inhibition. It exerted the marked antiproteinuric effect, maintained sodium reabsorption, leading to the decrease in its excretion, reduced natriemia on the background of normokalemia. The tincture reduced the anxiety of animals in the elevated plus maze test, this effect was evident when the tincture was combined with allopurinol; in this case the intensity of vegetative and emotional signs in the open field test was also reduced.                                                              Conclusions. Goutweed tincture does not enhance the toxicity of allopurinol under the conditions of the excessive intake of purine derivatives and proteins.