Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury

Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.

Effect of pyrrole derivatives on manifestations of inflammation in rats with chronic ulcerative colitis under prednisolone treatment

Background. Previously, we have detected the antitumor and anti-inflammatory activities of pyrrole-derived protein kinase inhibitors - MI-1 (1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino) -1H-pyrrole-2,5-dione 1) and D1 (5-amino-4-(1,3-benzothiazole-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one) using rat colon cancer model. Therefore, pyrrole derivatives was aimed at detecting the anti-inflammatory effect on the model of ulcerative colitis caused by acetic acid in rats. Materials and Methods. Prednisolone was used as a reference anti-inflammatory drug of glucocorticoid nature. It was administered intraperitoneally at a dose of 0.7 mg/kg. The compounds were administered in 2 h after the first administration of acetic acid. Total protein was estimated quantitatively, as described by Lowry et al., 1951. Content of the malonic dialdehyde, protein carbonyl groups, and the activity of antioxidant enzymes as indicators of colon mucosa redox status were measured spectrophotometrically. Statistical analysis of the results was performed using MS Excel-2013. Results and Discussion. In case of chronic colitis, the number of carbonyl groups and lipid peroxidation products in the colonic mucosa are increased, indicating the development of oxidative stress. The injection of pyrrole derivatives separately contributes to the approaching these indicators to normal. Adding prednisolone does not have this effect. Colitis has been shown to have a decrease in superoxide dismutase activity, which is a typical phenomenon for chronic inflammation and may indicate depletion of the enzyme. In case of colitis, alanine aminotransferase activity and the content of direct bilirubin are increased, which indicates a liver injury and are systemic manifestations of inflammation of the colon. Pyrrole derivatives help to reduce the liver injury, which indicates the restoration of normal alanine aminotransferase activity and direct bilirubin content. Conclusion. It has been found that at chronic colitis pyrrole derivatives reduce the manifestations of inflammation, contribute to the normal structure of the mucous membrane (comparative to prednisolone as a standard anti-inflammatory drug). It suggests their anti-inflammatory effectiveness, while an increase in total bilirubin under exposition to pyrrole derivatives may be a sign of the adverse effects on the rat’s liver.

Effects of single and 7-fold administration of a complex of albendazole with disodium salt of glycyrrhizic acid to hamsters infected with Opisthorchis felineus

The purpose of the research is to evaluate the effect of albendazole as part of the supramolecular complex with disodium salt of glycyrrhizic acid obtained by solid-phase mechanical treatment.Materials and methods. The anthelmintic activity of the complex and its effect on the host organism was assessed on hamsters infected with Opisthorchis felineus by single and 7-fold administration at 45 days after infection. After 21 days, we counted the number of helminthes in the liver, and conducted a morphometric analysis of the liver and spleen, and detected biochemically the activity of alanine aminotransferase and aspartate aminotransferase in the animals’ blood serum.Results and discussion. The number of O. felineus significantly decreased after 7-fold, but not a single, administration of albendazole (ABZ) and ABZ-Na2GA complex (1 : 10). The administrated substances had no effect on the weight gain of the animals and the daily consumption of the pellets. At the same time, ABZ only as part of the complex normalized the weight of the liver and spleen in hamsters infected with O. felineus and reduced the alanine aminotransferase activity. Consequently, a longer administration of ABZ as part of the complex with disodium glycyrrhizinate has not only a pronounced anthelmintic effect, but also improves some of the physiological parameters of hamsters to a greater extent than a pure substance.

Features of management of patients with liver diseases in the conditions of the COVID-19 pandemic

Liver dysfunction is common with COVID-19 infection, and the prevalence is higher in men as well as in the elderly. Manifestations of liver damage such as high aspartate aminotransferase and alanine aminotransferase activity, increased bilirubin levels, low albumin levels, and prolonged prothrombin time are associated with severe COVID-19 infection. Mortality in patients with diffuse liver diseases without cirrhosis with COVID-19 infection was 12 %, in the presence of liver cirrhosis up to 40%, decompensated liver cirrhosis up to 4363%. The mechanisms of liver damage in COVID-19 include direct hepatotoxicity and indirect liver damage (due to systemic inflammation with impaired immunity, sepsis, hypoxia, ischemia, coagulopathy, endotheliitis, right ventricular failure, worsening of the course of existing liver diseases, drug liver damage). Treatment of patients with diffuse liver diseases includes lifestyle and nutritional modification, the use of hepatoprotective drugs, and means of correcting the intestinal barrier (bibliography: 30 refs).

Cortical and vegetative regulation of aminotransferase activity in blood serum of dry sows under exposure to a technological stimulus

The article presents the results of studying the influence of cortical and vegetative mechanisms of regulation on the transaminase enzymes activity in blood serum of dry sows under exposure to a technological stimulus. The experiments were carried out on sows of large white breed of 3 years old. The results of research have shown that the indicators of conditioned reflex activity affect the activity of reamination enzymes in blood serum both under physiological conditions and after the exposure to a technological stimulus. According to the correlation analysis, the relationship between the strength and balance of cortical processes with serum alanine aminotransferase activity (r = 0.48–0.65; Р≤0.05–0.01), as well as the strength of cortical processes with aspartate aminotransferase activity (r = 0.51; P≤0.05). The significant influence (η2x = 0.23–0.36; Р≤0.01) of the balance of cortical processes on the activity of alanine aminotransferase in blood serum was established. Instead, the tone of the autonomic nervous system had a significant influence on the activity of reamination enzymes only after the exposure to a technological stimulus. In particular, the significant degree of influence (η2x = 0.28; P≤0.05) of sympathicotonia on the activity of alanine aminotransferase in blood serum on the 7th day after exposure to a technological stimulus was established.

ROLE OF 7-CHLORO-4-(PHENYLSELANYL) QUINOLINE IN THE TREATMENT OF OXALIPLATIN-INDUCED HEPATIC TOXICITY IN MICE

There is an increasing incidence of oxaliplatin (OXA)-induced hepatotoxicity. Therefore researchers’ attention has been drawn to therapeutic alternatives that may decrease OXA-induced hepatotoxicity. Studies indicate that oxidative stress plays a major role in OXA-induced liver injury. Since several pharmacological effects of 7-chloro-4-(phenylselanyl) quinole (4-PSQ) involve its antioxidant action, the hypothesis that this organoselenium compound could be promising for the treatment or prevention of hepatotoxicity induced by treatment with OXA was investigated. To test this hypothesis, male Swiss mice received OXA (10 mg/kg), on days 0 and 2, followed by the oral administration of 4-PSQ (1 mg/kg), on days 2 to 14. 4-PSQ reduced the plasma aspartate and alanine aminotransferase activity increased by exposure to OXA. The histopathological examination of the liver showed that 4-PSQ markedly improved OXA-induced hepatic injury. In addition, treatment with 4-PSQ reduced the oxidation of lipids and proteins (thiobarbituric acid reactive species levels and protein carbonyl content) and attenuated the increase of hepatic catalase and glutathione peroxidase activity caused by OXA. The inhibition of hepatic δ-aminolevulinic dehydratase activity induced by OXA was reverted by 4-PSQ. In conclusion, results indicate that 4-PSQ may be a good therapeutic strategy for attenuating OXA-induced liver damage.

Pleuroperitoneal true diaphragmatic hernia of the liver in a cat

A 2-year old female domestic shorthair cat was referred with intermittent vomiting. Laboratory analyses revealed only an elevated alanine aminotransferase activity. Plain thoracic radiographs showed a right-sided transdiaphragm protrusion of a liver lobe into the thoracic cavity. On abdominal ultrasound the diaphragm and liver parenchyma also presented a bulge towards the thoracic cavity. By cranial median laparotomy herniation of the quadrate liver lobe through the right aspect of the diaphragm into the thoracic cavity was confirmed. The protruding quadrate liver lobe was covered by intact parietal peritoneum. Following relocation of the liver lobe the defect was closed. Postoperatively the intermittent vomiting stopped. The purpose of this case report was to present plain radiography and abdominal ultrasonography as effective tools in the diagnosis of this rare and usually asymptomatic true herniation case along with its operative treatment.

Biochemical parameters of blood serum of dogs for ctenocephalidosis

One of the most common ectoparasitic diseases of domestic carnivorous animals is ctenocephalidosis caused by fleas of the genus Ctenocephalides. The peculiarity of this invasion is a chronic course associated with the constant attack of parasitic insects on the animal, accompanied by severe itching, the occurrence of alopecia, the development of eczema, dermatitis and the subsequent introduction of pathogenic microflora into the damaged tissue. The aim of the study was to investigate the effect of fleas of the genus Ctenocephalides on the biochemical parameters of the blood serum of invaded dogs. Three groups of animals were formed: a control (clinically healthy dog) and two experimental animals (infected by the parasitic insect Ctenocephalides spp.) with different intrusion rates. In blood serum determined: the content of total protein, albumin, total bilirubin, creatinine, urea, glucose, cholesterol, phosphorus, potassium, calcium, magnesium, alanine aminotransferase activity, aspartate aminotransferase, alkaline phosphate. Conducted studies found that rates the intensity of infestation significantly influence the changes that occur in blood serum infested dogs. The intensity of ctenocephalidosic infestation of up to 15 specimens of fleas in the animal in their blood serum showed a significant decrease in albumin content (by 22.37 %) compared to that in clinically healthy dogs. The intensities of xenophalphalous infestation of 16–47 specimens of fleas per animal in the serum of the infected animals showed a significant decrease in albumin (by 29.28 %), glucose (by 25.29 %), and cholesterol (by 35.59 %) relative to similar indicators clinically healthy animals. At the same time in the serum of the infested dogs the content of total bilirubin (by 15.73 %), as well as the activity of alanine aminotransferase (1.4 times), aspartate aminotransferase (1.4 times) and alkaline phosphatase (2 times). The results of the experimental data extend the already existing data on the pathogenesis of fleas parasites in dogs, and will also allow the effective treatment of diseased animals.