ANTIOXIDANT POTENTIAL OF ADEMETIONINE IN GENTAMICINE NEPHROPATHY PROGRESSION

Abstract

Acute kidney injury has been globally considered as a serious medical issue. Its incidence rate is increasing over the years despite the introduction of new therapies, the cause of which is often a side effect to drugs, or due to the impact of toxins, trauma. Nephrotoxicity is one of the most important side effects of aminoglycoside antibiotics, and on gentamicin, in particular. Despite rigorous patient monitoring, this type of nephrotoxicity appears in 10–30% of therapeutic courses. Therefore, searching for new therapies, which would be able to prevent or decrease toxic kidney injury during the treatment with aminoglycosides is quite relevant. Ademetionine is an amino acid derivative, which possesses various effects such as antioxidant, membrane stabilizing, anti-inflammatory and regenerative.
 Aim of the research is to study an antioxidative activity of ademetionine in conditions of gentamicin nephropathy progression in rats. Materials and methods. Research was conducted on non-linear mature white rats weighting 130-180 g, randomly divided into 3 groups (n = 7): I group included intact control animals, II group included rodents with gentamicin nephropathy (injection of 4% Gentamicin sulphate solution in a dosage of 80 mg/kg for 6 days), III group involved the rats receiving ademetionine («Abbott SpA», Italy) in a dosage of 20 mg/kg. Peroxidation processes in blood and kidneys were evaluated by the content of active products that react with thiobarbituric acid and oxidative modification of proteins levels, antioxidant defence was assessed by catalase and glutathione peroxidase activity, SH-groups and ceruloplasmin content.
 Results. In the course of experimental studies on the model of gentamicin nephropathy, the expressive antioxidant activity of ademetionine was proven: it was demonstrated by reducing the intensity of lipid peroxidation (a decrease in the content of active products that react with thiobarbituric acid) and proteins (a decrease in the content of oxidative modified proteins) in the blood and kidney homogenate, next with increased activity of the enzymatic link of antioxidant protection (glutathione peroxidase and catalase) and non-enzymatic (ceruloplasmin and compounds with SH-groups). The antioxidant potential of ademetionine has been confirmed by an increase in the antioxidant-prooxidant index in kidney tissue and a significant decrease in the index of oxidative stress in the blood of treated animals.
 Conclusion. Thus, the results of experimental studies indicate the antioxidative effect of ademetionine in modelled gentamicin nephropathy, and point out the necessity of further studying its potential nephroprotectective properties.