Perspectives for the use of morpholinium tiazotate as a pharmacotherapy for hepato-cardiac disorders

Experimental, clinical, and epidemiological data suggest a strong connection between chronic liver disease and cardiovascular disease (CVD). Oxidative and nitrosative stress is a major pathogenetic mechanism shared between the two groups of diseases, which is the rationale behind the use of antioxidants in patients with comorbidities. This review presents a pharmacological profile and summarizes the evidence for the effectiveness and safety of morpholinium tiazotate, an antioxidant, endotheliumprotective, and antihypoxic agent, in patients with liver diseases, CVD, and combinations thereof. In vitro, morpholinium tiazotate scavenges reactive oxygen and nitrogen species, slows down the use of endogenous antioxidants, inhibits pro-inflammatory macrophage polarization and cell apoptosis. Experimental studies have found this drug to stabilize the nitroxidergic system and improve NO bioavailability to a greater extent than direct NO donors, and increase the effectiveness of energy production in ischemia via stimulating glycolysis and citric acid cycle, sustaining aerobic cellular respiration, and inhibiting fatty acid β-oxidation. The compound’s pleiotropic effects include the decrease in atherogenic serum lipid fraction levels, local and systemic inflammation, maintenance of cell membrane integrity, and desensitization of myocardial β adrenergic receptors to catecholamines. Clinical trials in CVD patients evidence that morpholinium tiazotate improves the electroand echocardiographic parameters, decreases the number and duration of ischemic episodes, frequency of cardiac arrhythmias, need for nitrate use, and physical exercise tolerance. In subjects with liver disease (non-alcoholic fatty liver disease, alcoholic liver disease), the drug reduces the symptoms of asthenia, decreases serum levels of cytolysis and cholestasis biomarkers, fatty liver index, and quantitative cardiovascular risk predictors. Current evidence supports the use of morpholinium tiazotate for the treatment of patients with non-alcoholic fatty liver disease and cardiovascular comorbidities.

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