Pharmacological correction of endothelial dysfunction using ademethionin and taurine

Abstract

Introduction: Рharmacological correction of endothelial dysfunction is a urgent problem of modern medicine. Materials and methods: Endothelial dysfunction was simulated in male rats using the e-NOS inhibitor L-NAME (25 mg/kg/day intraperitoneally, for 7 days). Simulation of ADMA-like preeclampsia was performed by intraperitoneal injection of L-NAME to females in the same doses for 7 days (14-20th days of pregnancy). These pathologies were corrected by administering ademethionine in dose 150 mg/kg and taurine at a dose of 260 mg/kg, as well as their combination at the same doses, intragastrically, through an atraumatic probe, once a day. Results: In the group with use of taurine at a dose of 260 mg/kg the coefficient of endothelial dysfunction decreased to the level of intact animals. Use of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg combined resulted in the most pronounced endothelioprotective effect on the ADMA-like preeclampsia model. The coefficient of endothelial dysfunction decreased more than when using monotherapy of these drugs. Morphological studies of myocardiocytes showed that the combination of ademethionine at a dose of 150 mg/kg and taurine at a dose of 260 mg/kg prevented an increase in the cross-section of cardiomyocytes. Discussion: Possibly, ademethionine and taurine have an endothelioprotective effect because of their ability to decrease hyperhomocysteinemia. Conclusion: The investigated drugs showed pronounced endothelioprotective activity and can be recommended for further pre-clinical studies.