Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.

The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.

Blood ACE2 Protein Level Correlates with COVID-19 Severity.

ACE2's impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects of the main risk factors and comorbidities, we involved post-COVID-19 patients in Ternopil region (Ukraine). The recruitment period was from July 2020 to December 2021. Medical records, treatment modalities, and outcomes were recorded and analyzed. The serum human ACE2 protein was measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis was performed with SPSS21.0 software (SPSS Inc., Chicago, IL, USA). The level of the ACE2 serum protein was significantly higher (p < 0.001) in patients with mild symptoms compared to a more severe course of the disease, and inversely had changed from 1 to 90 days after recovery. In patients with mild COVID-19, ACE2 levels significantly decreased over time, while among critical patients, it increased by 34.1 percent. Such results could be explained by ACE2 shedding from tissues into circulation. Loss of the membrane-bound form of the enzyme decreases the virus' entry into cells. Our studies did not identify a sex-related ACE2 serum level correlation. The most common comorbidities were hypertension, cardiovascular diseases, respiratory diseases, and diabetes mellitus. All abovementioned comorbidities except respiratory diseases contribute to the severity of the disease and correlate with ACE2 blood serum levels.

Natural Ingredients to Improve Immunity.

The immune system protects the body from infectious agents such as bacteria, viruses, or fungi. Once encountered with pathogens or antigens, the innate and adaptive arms of the immune system trigger a strong immune response to eliminate them from the system and protect the body. Thus, well-balanced immunity is pivotal for maintaining human health, as an insufficient level of immune defense leads to infections and tumors. In contrast, the excessive functioning of the immune system causes the development of autoimmune diseases and allergies. Strong immunity requires adequate nutrition, dietary interventions, and sufficient intake of certain vitamins (vitamin C, vitamin D, and folic acid) and minerals (magnesium, zinc, and selenium). Therefore, nutritional and micronutrient deficiencies lead to compromised immunity. Several natural ingredients have shown potent immunomodulatory properties. The immune-enhancing properties of many plants and fungi are due to containing bioactive phytoconstituents such as polyphenols, terpenoids, ß-glucans, vitamins, etc. Probiotics and prebiotics can be used as innovative tools to reduce intestinal inflammation and downregulate hypersensitivity reactions. Plant sources of melatonin, a multifunctional molecule with proven anti-inflammatory and immunomodulatory properties, have been discovered relatively recently. The bioactive compounds augment the immune response by directly increasing the cytotoxic activity of natural killer cells, macrophages, and neutrophils. Many phytoconstituents prevent cell damage due to their powerful antimicrobial, antioxidant, and anti-inflammatory properties. The present review attempts to understand the molecular mechanisms underlying the immune-enhancing properties of some bioactive compounds from plants, fungi, animals, microorganisms, and other natural sources.

Experimental cirrhosis: liver morphology and function.

OBJECTIVE: The aim was to establish the morphofunctional changes of liver in the experimental cirrhosis. PATIENTS AND METHODS: Materials and methods: The research was conducted on 24 white male Wistar rats. Experimental cirrhosis of the liver was simulated by oral administration of CCl4 2 g/kg 2 times weekly for three months. From the selected fragments of the liver, histological specimens were done according to the conventional method and examined by light microscopy. The activity of the enzymes of cytolysis and cholestasis (ALT, AST, alkaline phosphatase), the content of components of bile (cholesterol, bilirubin and bile acids) were determined in the serum. In the blood and liver were determined the content of the final products of metabolism of nitric oxide: NO2 - and NO3 -; in the blood - the content of ceruloplasmin, lactate, pyruvate, middle molecular-weight protein MWP1 and MWP2. In the liver - the activity of succinate dehydrogenase (SDG) and cytochrome oxidase (CHO), N-demethylase and p-hydroxylase microsomal activity. The state of the system of prooxidants-antioxidants was judged by the content in the liver of thiobarbituric acid reactive substance (TBARS), lipid hydroperoxide (LHP), concentration of sulfhydril group (GSH), catalase activities (CAT), superoxide dismutase (SOD). The content of endothelial (eNOS) and inducible (iNOS) NO synthases, the concentration of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were determined by the enzyme immunoassay. RESULTS: Results: Cirrhosis of the liver, which is morphologically confirmed by the presence of prominent sclerosis in the periportal zones and the formation of umbel, is accompanied by the development of cytolysis and cholestasis processes with an increase in the content of components of bile in the blood (cholesterol, bilirubin and bile acids). An increase in the content of lipoperoxidation products and disturbance of the state of the enzymatic and non-enzymatic units of the antioxidant system, decrease in the activity of mitochondrial (succinate dehydrogenase and cytochrome oxidase) enzymes have been established. The activity of the detoxification processes decreases, namely the inhibition of N-demethylase and p-hydroxylase activity of the liver microsomes, so the manifestations of endotoxicosis increase. This is accompanied with decreased content of endothelial and an increased content inducible NO synthase, a concentration of a stable metabolite of nitric oxide nitrite anion in the blood increase and a decrease in the liver. CONCLUSION: Сonclusions: Experimental CCl4 cirrhosis is characterized morphologically by sclerosis in the periportal zones and the formation of umbao. The metabolic and functional cirrhotic liver is characterized by cytolysis and cholestasis activation, inhibition of detoxication, prooxidant-antooxidant, including nitrooxidative, disbalance.

Hepatoprotective Effect of Melatonin in Toxic Liver Injury in Rats.

Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley male rats were split into three equal groups and given carbon tetrachloride (CCl4), 2 g/kg (CCl4 group) or the same dose of CCl4 and melatonin, 10 mg/kg (CCl4/melatonin group) or saline (control group). The effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in serum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in all three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine and thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in serum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations were decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate dehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum: NO2-by 37.9%; NO3-by 29.2%. There was no significant difference in content NO2-in the liver, but concentration of NO3-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both in serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in serum, nor in liver. The histopathological liver lesions observed in the CCl4/melatonin group were less severe than those seen in the CCl4 group. Conclusions: we demonstrated an ameliorating effect of melatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and histopathological lesions in the liver in rats with CCl4-induced hepatitis.