Pharmacological correction of the sequelae of acute alcohol-induced myocardial damage with new derivatives of neuroactive amino acids coupled with the blockade of the neuronal NO synthase isoform

Introduction: Acute alcohol intoxication (AAI) induces a number of myocardial disorders, which result in mitochondrial dysfunction in cardiomyocytes, oxidative stress, and decreased cardiac contractility. Nitric oxide produced by the nNOS is one of the major modulators of cardiac activity. New derivatives of GABA (RSPU-260 compound) and glutamate (glufimet) can be potentially regarded as such agents as the interaction between the NO system and the GABA and glutamatergic systems has been proved. Materials and methods: All the studies were performed on female white Wistar rats, aged 10 months, whose weight was 280–320g AAI intoxication was modeled of 32% ethanol (gavage, 4g/kg). Results and discussion: Glufimet and the RSPU-260 compound caused a significant improvement in myocardial contractility, increased oxygen consumption in the V3 state according to Chance, raised the respiratory control ratio and decreased the intensity of LPO intensity. Their effectiveness exceeded that of mildronate, their comparator. nNOS inhibition resulted in a pronounced aggravation of oxidative stress implicated in MDA accumulation in cardiac mitochondria and decreased activity of SOD; myocardial contractility and mitochondrial function indicators did not show a significant difference from the control group. The compounds under study coupled with nNOS inhibition had a cardioprotective effect. Conclusion: Glufimet and the RSPU-260 compound, derivatives of neuroactive amino acids, have a pronounced cardioprotective effect, restrict LPO processes, enhance SOD activity, improve the mitochondrial respiratory function after acute alcohol intoxication when coupled with neuronal NO-synthase inhibition, the expression of which persists after AAI. Graphical abstract

<i>Listeria monocytogenes</i> ST37 Distribution in the Moscow Region and Properties of Clinical and Foodborne Isolates

Listerias of the phylogenetic lineage II (PLII) are common in the European environment and are hypovirulent. Despite this, they caused more than a third of the sporadic cases of listeriosis and multi-country foodborne outbreaks. L. monocytogenes ST37 is one of them. During the COVID-19 pandemic, ST37 appeared in clinical cases and ranked second in occurrence among food isolates in the Moscow region. The aim of this study was to describe the genomic features of ST37 isolates from different sources. All clinical cases of ST37 were in the cohort of male patients (age, 48–81 years) with meningitis–septicemia manifestation and COVID-19 or Influenza in the anamnesis. The core genomes of the fish isolates were closely related. The clinical and meat isolates revealed a large diversity. Prophages (2–4/genome) were the source of the unique genes. Two clinical isolates displayed pseudolysogeny, and excided prophages were A006-like. In the absence of plasmids, the assortment of virulence factors and resistance determinants in the chromosome corresponded to the hypovirulent characteristics. However, all clinical isolates caused severe disease, with deaths in four cases. Thus, these studies allow us to speculate that a previous viral infection increases human susceptibility to listeriosis

Changes in the respiratory function of the heart and brain mitochondria of animals after chronic alcohol intoxication affected by a new GABA derivative

Introduction: Chronic ethanol consumption leads to significant functional and structural changes in the mitochondria of the heart and brain, increasing generation of reactive oxygen species. Therefore, the search for substances, which improve the functional state of the mitochondria and, meantime, reduce the oxidative stress, is relevant. Materials and methods: 10-months-old Wistar female rats were used in the experiments. Chronic alcohol intoxication (CAI) was modelled by replacing drinking water with a 10% ethanol solution containing sucrose (50 g/L) for 24 weeks. Four groups were formed: 1 – intact animals; 2 – animals after chronic alcohol consumption; 3 – rats after CAI which were administered RSPU-260 (25 mg/kg); 4 – rats after CAI which were administered the reference drug Mildronate (50 mg/kg). The intensity of lipid peroxidation (LPO) and the rate of oxygen consumption in various metabolic states were determined. Results and discussion: Administration of the compound RSPU-260 to the animals exposed to alcohol over a long period of time resulted in an increase in both the rate of oxygen consumption (state 3) and the respiratory control ratio (RCR) of the mitochondria of heart and brain cells. The use of a GABA derivative promoted a decrease in malonic dialdehyde in the mitochondria of the heart and brain. Total SOD activity in the mitochondria of heart cells was significantly increased in the groups of rats treated with RSPU-260. In terms of efficiency, the compound RSPU-260 was comparable to the reference drug Mildronate. Conclusions: The compound RSPU-260, and the reference drug Mildronate improve mitochondrial oxidative phosphorylation in heart and brain cells, the functioning of antioxidant enzymes in animals after CAI, and can be used to correct alcoholic damage to these organs