CCl4 Solution Research Articles

Potential hepatoprotective properties of synthetic derivatives of thiourea — 2-aminobenzothiazole and IEM-2320

BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

Echinacoside Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Modulating the NF-κB/NLRP3 Inflammasome Pathway.

The purpose of this study was to investigate the protective effect of echinacoside (Ech) on carbon tetrachloride (CCL4)-induced chronic liver injury in rats and its potential mechanisms. Thirty Sprague-Dawley (SD) rats were randomly divided into five groups: the Control group, the CCL4 group, the CCL4 + Ech 25 mg/kg group, the CCL4 + Ech 50 mg/kg group, and the CCL4 + Ech 100 mg/kg group. The rats were injected intraperitoneally with CCL4 solution twice a week to induce chronic liver injury, and Ech intervention lasted for 4 weeks. After the intervention, the liver and blood samples from rats were collected for subsequent analysis. Ech effectively reduced the levels of serum liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, alkaline phosphatase, and total bilirubin), attenuated the hepatocyte degeneration and necrosis, improved the severity of liver fibrosis, and inhibited the local inflammatory response of the liver in a dose-dependent manner. Ech effectively mitigated CCL4-induced chronic liver injury in rats by downregulating the NF-κB/NLRP3 inflammasome pathway.

Computational insights into solvent polarity associated excited state behaviour for 2-(1H-benzoimidazol-2-yl)−5-diethylamino-phenyl fluorophore

Inspired by the mesmerising charm emanating from the precisely controlled attributes displayed by 2-(1H-benzoimidazol-2-yl)−5-diethylamino-phenyl (HDP) and its derivatives in the domains of photochemistry and photobiology, our present undertaking predominantly focuses on exploring the complexities of light-triggered excited state reactions for HDP fluorophore dissolved in solvents with diverse levels of polarity. Initially, we performed molecular structure optimisation at various stages of the proton transfer process and collected data on bond length, bond angle, and core-valence bifurcation (CVB) index for the molecular framework. Subsequently, infrared (IR) vibrational spectra were analysed to evaluate the reinforcement of hydrogen bonds in different solutions. Furthermore, the investigation of orbital transitions and potential energy curves has led to the conclusion that the ESIPT process of HDP molecules is most likely to occur in nonpolar ccl4 solution, followed by chloroform solution; acetonitrile ranks last. In essence, the nonpolar aprotic solvents are more conducive to facilitating the ESIPT process. This research aims to contribute towards advancements in new luminescent materials and prove valuable in display technology and medical imaging fields while also promoting related technological development.

Cyclic Silicon Organic Copolymers: Synthesis and Investigation. Review

This paper considers the synthesis and investigation of cyclic silicon-organic polymers with mono- and polycyclic fragments in the side chain. For obtaining monocyclic polymers, the hydrosilylation reaction of 1-hydro-3-vinylhexamethylcyclotetrasiloxane was used. The reaction was conducted in a CCl4 solution at 75°C in the presence of Speier’s catalyst (H2PtCl6  6H2O) to produce a viscous-flow at room temperature polymer. The polymers were studied by NMR spectroscopy. Poly(carbosiloxane) with cyclic fragments in the methyl-siloxane backbone was synthesized by the hydride polyaddition of divinylorganocyclosiloxane with dihydrodimethylsiloxane. A semi-quantitative assessment conducted using NMR spectroscopy revealed the ratio of isomeric 1,3- and 1,5-cyclic structures as 1:1. X-ray diffraction studies indicated that copolymers are single-phase amorphous systems. Also, in the review, synthesis and studies of carbosiloxane copolymers containing flexible dimethylsiloxane and decaorganotricyclodecasiloxane fragments in the backbone are discussed. Hydride polyaddition of divinyl-containing compounds was carried out for -dihydridedimethylsiloxanes of various lengths. The synthesized copolymers were characterized by the X-ray diffraction method and TGA.

The curative effect of ethanolic extract of Moringa oleifera leaf in an animal model of liver fibrosis

Studies about the prevention effect of Moringa oleifera on liver fibrosis has been reported. However, its curative effect has not been reported, yet. This study was conducted to evaluate the curative effect of M. oleifera leaf extract on liver fibrosis. It was a laboratory experimental study with a post-test-only control group design. Rats were divided into 5 groups i.e. normal control which received intraperitoneally injections of 1 mL/kg BW of 0.9% NaCl solution twice a wk for 11 wk. Liver fibrosis control which received intraperitoneally injections of 1 mL/kg BW of 10% CCl4 solution twice a wk for 11 wk. Three M. oleifera treatment group which received intraperitoneally injections of 1 mL/kg BW of 10% CCl4 solution twice a wk for 11 wk continued by M. oleifera leaf ethanolic extract at dose of 600 mg/kg BW daily for 3 (MO3), 6 (MO6), and 10 (MO10) wk, respectively. The liver fibrosis level was assessed based on the METAVIR score. Histopathological analysis of liver tissues demonstrated that the 11-week CCl4 induction successfully resulted in liver fibrosis in rats (F3 and F4). The administration of M. oleifera leaf ethanolic extract decreased METAVIR scores ranged from F3 to F1. The optimal reduction of the METAVIR scores (F1) was observed in MO3 group after 6 wk administration (p<0.05). It was indicated that M. oleifera leaf ethanolic extract ameliorated liver fibrosis. In conclusion, M. oleifera leaf ethanolic extract has a curative effect against liver fibrosis.

Sonochemical Analysis of Methylene Blue with Additives and ZnO Nanoparticles in Aqueous Medium

The use of ultrasound was found to be a very suitable and effective method for the degradation of hazardous dyestuffs. The degradation of dye molecules in aqueous media in the presence of various additives by ultrasonic irradiation was investigated in order to clarify the degradation mechanism. In this investigation, Methylene Blue (MB) has been used as a representative of azo dye and inorganic salts like NaCl and Na2SO4 were used as additives. Besides degradation in presence of CCl4 and H2O2 solutions were observed. ZnO nanoparticle was also used for the investigation of degradation. The volume of all solutions was 100ml containing 25mg/L of MB. The sonication of dye molecules were conducted for 0, 5, 15, 25 minutes. The degradation mechanism was discussed in details adopting UV- visible spectra. From the experiments it is clear that the acidic condition is favorable for dye degradation. Evaluating the results we have also found that all additives aided the degradation comparatively higher or lower the extent depending on their used amount in solution. So, it is a clear indication that azo dyes from waste water can be efficiently removed by using sonochemical irradiation method under acidic condition

Combined Compression of Stimulated Brillouin Scattering and Laser–Induced Breakdown Enhanced with Sic Nanowire

In this paper, the laser pulse time compression technique, based on stimulated Brillouin scattering (SBS) and passive laser–induced breakdown (LIB) series technology, is investigated. By doping a SiC nanowire in a CCl4 solution of an LIB breakdown medium, the LIB generation threshold is reduced, and the stability of the LIB compression output is improved. When OD is 0.2, the output pulse width is 254.4 ps, and the corresponding energy conversion efficiency and pulse compression rate are 34.2% and 50.2%, respectively. Our experiment proves the feasibility of this scheme.

Complexes of phosphine oxides with substituted phenols: hydrogen bond characterization based on shifts of PO stretching bands.

In this work IR spectral characteristics of PO groups are used to evaluate the strength of OHO hydrogen bonds. Three phosphine oxides: triphenylphosphine oxide, tributylphosphine oxide and hexamethylphosphoramide are investigated as proton acceptors. The results of the experimental IR study and DFT calculation of 30 complexes formed by phosphine oxides with various substituted phenols or CF3CH2OH in CCl4 solution at room temperature are reported. We show that the PO vibrational frequency changes non-linearly upon hydrogen bond formation and strengthening and that the shift of the PO band could be used for the estimation of hydrogen bond strength in complexes with phosphine oxides. The accuracy of these estimations and the influence of solvation effects on the main characteristics of complexes are discussed.

An IR spectroscopic investigation of blue shifting C–H⋯Cl hydrogen bonds in room temperature solution: Homomeric and mixed dimers of CHCl3 and CH2Cl2

CH···Cl H-bonded homomeric and mixed dimers of CHCl3 and CH2Cl2 have been studied in room temperature CCl4 solution by observing spectral shift of νC−H fundamental transitions using IR spectroscopy. νC−H bands were found to show blue shift by 1.1 to 3.3 cm−1 upon CH···Cl H-bond formation in all the studied dimers. The findings were reinforced by observing νC−D spectral shifts for the corresponding dimers of the deuterated compounds, i.e., CDCl3 and CD2Cl2. νC−D bands also showed only blue shift within the range of 0.2 to 4.1 cm−1. All the experiments have been performed in another nonpolar solvent (C2Cl4) and the results were in close agreement with each other. Quantum chemical calculations predict multiple stable conformers for each of the dimers studied. In all the cases, the most stable conformers were solely C‒H···Cl H-bonded, confirming the observed νC−H spectral shifts to be brought about by intermolecular C‒H···Cl H-bond formation.

GENDER DIFFERENCES IN THE EFFECT OF ANTIULCER DRUGS AND PLACENTA CRYOEXTRACT ON THE INTENSITY OF LIPID PEROXIDATION AND THE ACTIVITY OF THE ANTIOXIDANT SYSTEM IN EXPERIMENTAL HEPATITIS WITH ETHANOL-INDUCED CIRRHOSIS

Introduction. It is well recognized that drug metabolism products in the liver can induce oxidative stress and mitochondrial dysfunction, leading to the development of hepatocellular injury. As a potential agent capable of counteracting the hepatotoxic effects of drugs, we focused our attention on a domestic biotechnological preparation – cryopreserved placental extract (CPE).
 The aim. To characterize gender differences in the effect of esomeprazole, clarithromycin, metronidazole (E/C/M), and CPE on the intensity of lipid peroxidation and the activity of the antioxidant system in tetrachloromethane (CCl4) hepatitis with a background of ethanol-induced cirrhosis (ETCM).
 Materials and methods. The study was conducted with varying levels of sex hormones on 112 male and female rats. Chronic ETCM was induced by administering a 50.0% oil solution of CCl4 at a dose of 8 ml/kg body weight of the animals twice a week, in combination with a 5.0% ethanol solution for drinking over a period of 45 days. The content of TBA-RP in liver homogenates was determined spectrophotometrically by the method described by Asakawa T. et al. Catalase activity in liver homogenates was determined spectrophotometrically according to the method of Korolyuk M.A. and co-authors.
 Results. The most pronounced increase in lipid peroxidation processes was observed in females with chronic ETCM-induced liver damage and administration of antiulcer drugs following ovariectomy, resulting in a TBA-RS content of 36.1±2.79 μmol/kg of tissue. Administration of E/C/M in animals with chronic liver damage led to a suppression of the antioxidant system, as evidenced by a decrease in catalase activity in liver tissues.
 Conclusion. The combined use of anti-ulcer drugs and CPE on the background of chronic ETCM mitigated the activation of lipid peroxidation processes, which was indicated by a statistically significant (p < 0.001) 2.7-fold lower content of TBA-RP in liver homogenates. Additionally, it was established that the administration of CPE was accompanied by a statistically significant increase in catalase activity in females, more prominently than in males. In females without changes in hormonal status, the introduction of CPE resulted in a growth (p < 0.001) of catalase activity by 75.0%, with the most significant increase observed in females after ovariectomy – catalase activity statistically significantly (p < 0.001) increased by 2.6 times compared to the indicators of females not administered with CPE. The administration of CPE in female rats without altering hormonal status was accompanied by a twofold (p < 0.01) increase in the antioxidant-prooxidant index compared to male rats, indicating more pronounced antioxidant properties of CPE in female rats.

Immunopharmacological aspects of studying immunotropic properties of a novel biocompound

The article presents an experimental study of immunotropic activity of a new compound, a metabiotic, based on metabolites (biologically active substances) produced by a of saprophytic Bacillus subtilis B-9909 strain, being safe for health and standardized at Russian National Collection of Industrial Microorganisms (RNCIM). The aim of our study was to experimentally evaluate the immunotropic effects of metabolites produced by the probiotic Bacillus subtilis B-9909 upon the parameters of cellular immunity tested in the animal model of induced toxic liver damage. The metabolites were isolated from the cultural liquid of Bacillus subtilis culture (RNCIM strain B-9909) during its deep cultivation in a medium containing hydrochloric acid hydrolyzate of soy flour, or pancreatic hydrolyzate of casein. At 16-18 hours of cultivation, the cells were in the exponential growth phase. The indices of cellular status were studied in experimental groups of animals, when assessing therapeutic efficacy of an experimental metabiotic sample, as compared to a group of laboratory animals treated with the reference drug (ursosan). We assessed the quantitative indicators of blood as follows: determination of phagocytic activity (FA) of peripheral blood neutrophils; measurement of metabolic activity in peripheral blood neutrophils by means of NBT-test; quantitative determination of T and B lymphocytes; the number of antibody-forming cells (AFC). Liver damage was studied in a model of acute toxic hepatitis in albino rats. Experimental toxic hepatitis was induced by 40% solution of CCl4 in vaseline oil injected intragastrically for 2 weeks at the dose of 0.2 g/kg. The results of experimental studies showed activation of phagocytic activity by peripheral blood neutrophils at the early terms of experiment, being also confirmed by the results of NBT-testing. Moreover, at the early observation terms, a significantly increased representation of T and B lymphocyte populations as well as AFC numbers, were revealed thus suggesting activation of all components of cellular immunity in response to the carbon tetrachloride toxicity. Thus, the reported studies on the cellular status of laboratory animals treated with metabolites produced by probiotic microorganisms of the genus Bacillus subtilis (B-9909) on laboratory animals with toxic liver damage allow us to conclude that the test sample of this metabiotic preparation exerts a significant immunomodulatory effect, when compared with ursosan. This evidence allows us to consider this compound a promising candidate drug for a new hepatoprotector with immunotropic effect.

ANTIOXIDANT ACTIVITY AND ENERGY PROTECTIVE EFFECT OF HEDYSARUM ALPINUM L. EXTRACT IN ACUTE CCL4-INDUCED HEPATITIS

Relevance. The course of physiological processes in the norm is significantly influenced by the pro- and antioxidant, as well as the energy status of the body. In the liver, biochemical disturbances in the functioning of these systems contribute to the development or aggravate the course of patholog-ical conditions such as chronic hepatitis, cholelithiasis, chronic cholecystitis, etc. In this regard, the assessment of the influence of the studied herbal remedies that have a hepatoprotective effect on energy metabolism and the state of the antioxidant system of the body in experimental pathological processes is still relevant. The purpose of the study was to evaluate the effect of Hedysarum alpinum L. dry extract on antioxidant status and energy metabolism in white rats with acute carbon tetrachloride-induced hepatitis. Material and methods. The studies were carried out on white Wistar rats. Acute carbon tetrachloride hepatitis was induced by subcutaneous injec-tion of a 50% oily solution of CCl4 for 4 days at a dose of 1.0 ml/kg. The dry extract H. alpinum was administered per os to animals at doses of 100 and 200 mg/kg. On the 7th and 14th days of the experiment, the energy metabolism and antioxidant status of the liver were assessed. The content of ATP, lactate, pyruvate, GSH the concentration of malondialdehyde (MDA), the activity of catalase, glutathione peroxidase, glutathione reductase, super-oxide dismutase (SOD) in the liver homogenate were determined. The evaluation of the antiradical activity of the studied agent was carried out in vitro: binding of 2,2-diphenyl-1-picrylhydrazyl (DPPH˙), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS˙+). Results. The dry extract H. alpinum was administered to animals at doses of 100 and 200 mg/kg, increases the activity of SOD, catalase, glutathione peroxidase, glutathione reductase and the content of GSH, reduces the content of MDA, increases the content of ATP, reduces the level of lactate; cor-rects the lactate/pyruvate ratio compared to the control. The dry extract of H. alpinum demonstrated the most pronounced antioxidant activity and en-ergy-protective effect at a dose of 200 mg/kg. The extract of H. alpinum characterized by a pronounced radical-binding activity against DPPH˙ and ABTS˙+ (IC50DPPH˙=25.1 µg/ml; IC50ABTS˙+=47.1 µg/ml), which was due to the high content in its composition of phenolic compounds (2-C-β-D-glucopyranosyl-1,3,6,7-tetraoxyxanthone, rutin, catechins, xanthones), flavonols and polysaccharides. Conclusions. The dry extract H. alpinum at doses of 100 and 200 mg/kg reduces the intensity of oxidative stress and corrects the state of energy metabolism in carbon tetrachloride-induced acute liver injury in white rats, showing a pronounced antioxidant, antiradical and energy-protective effects.

Hepatocyte-specific knockout of HIF-2α cannot alleviate carbon tetrachloride-induced liver fibrosis in mice.

The effects of hypoxia inducible factor-2α (HIF-2α) deficiency on liver fibrosis have not been demonstrated in a fibrosis model induced by carbon tetrachloride (CCl4). We aimed to examine whether hepatocyte-specific HIF-2α deletion could ameliorate CCl4-induced liver fibrosis in mice. Hepatocyte-specific HIF-2α knockout mice were created using an albumin promoter-driven Cre recombinase. HIF-2α knockout (KO) mice and floxed control wild-type (WT) mice were fed a normal diet (ND) and received either twice weekly intraperitoneal injections of CCl4 solution (CCl4 dissolved in olive oil) or the corresponding amount of olive oil for 8 weeks. The indicators of liver function, glucose and lipid metabolism, and liver histology were compared among the different groups. Hepatocyte-specific HIF-2α knockout had no effect on the growth, liver function, glucose or lipid metabolism in mice. CCl4-treated KO and WT mice had a similar pattern of injury and inflammatory cell infiltration in the liver. Quantification of Masson staining, α-smooth muscle actin (α-SMA) immunohistochemistry, and the hydroxyproline (HYP) content revealed similar liver fibrosis levels between KO and WT mice injected intraperitoneally with CCl4. Immunohistochemistry analysis suggested that HIF-2α was mainly expressed in the portal area and hepatic sinusoids but not in hepatocytes. Bioinformatics analyses further indicated that HIF-2α expression was neither liver specific nor hepatocyte specific, and the effect of HIF-2α in hepatocytes on liver fibrosis may not be as important as that in liver sinuses. Hepatocyte HIF-2α expression may not be a key factor in the initiation of liver fibrogenesis, and hepatocyte-specific deletion of HIF-2α may not be the ideal therapeutic strategy for liver fibrosis.

Gender determinism of the effect of placenta cryoextract on the hepatotropic effects of esomeprazole, clarithromycin and metronidazole in chronic liver damage

Current regimens for the eradication of Helicobacter pylori infection include bismuth drugs, proton pump inhibitors, and a combination of 2–3 antibacterial drugs. Uncontrolled use of antibacterial agents as part of eradication schemes increases the risk of developing their unwanted drug reactions, in particular, hepatotoxicity. As a means with potentially hepatoprotective activity, our attention was drawn to placental cryoextract.
 The purpose of the study. To characterize the gender aspects of the hepatotropic action of placenta cryoextract in tetrachloromethane hepatitis with background ethanol-induced cirrhosis and liver damage by antiulcer agents.
 Materials and methods. Research was conducted on 112 male and female rats. Tetrachloromethane hepatitis with background ethanol-induced liver cirrhosis was reproduced by injecting an oil solution of CCl4 in combination with a 5.0% ethanol solution for 45 days. Modulation of the content of sex hormones was achieved by surgical ovariectomy or testectomy.
 Results and discussion. Administration of esomeprazole, clarithromycin, and metronidazole in chronic liver damage in animals without changes in hormonal status led to a statistically significant (p=0.01) 27.6% increase in the level of bilirubin in homogenates of liver tissues in female rats (78.7±4.5 mmol/l) than in males. The greatest decrease in the content of bilirubin (41.7%, p<0.001) with the use of cryoextract of the placenta was noted in castrated female rats with simulated tetrachlormethone hepatitis with background ethanol-induced cirrhosis of the liver, which were injected with antiulcer agents.
 Conclusions. Administration of cryoextract of the placenta has a pronounced hepatoprotective effect in animals of both sexes. In male rats with no change in hormonal status with simulated liver injury and the administration of antiulcer drugs, placenta cryoextract therapy was more effective than in female rats, as indicated by a more than 1.6-fold decrease in the content of bilirubin in the liver homogenates of male rats (43.1%, p<0.001) than in females (27.4%, p<0.01).

Sodium Hydrosulfide Modification of Mesenchymal Stem Cell-Exosomes Improves Liver Function in CCL4-Induced Hepatic Injury in Mice.

Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury. Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (1 μmol) and exosomes were isolated using an exosome isolation kit. Male mice (8-12 weeks old) were randomly divided into four groups (n=6): 1-control, 2-PBS, 3- MSC-Exo, and 4- H2S-Exo. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection. Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis. MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes.

Lyciumbarbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways.

The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lyciumbarbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl4). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl4 solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl4-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase II detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I‒V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.

Investigating the Photodissociation Dynamics of CF2BrCF2I in CCl4 through Femtosecond Time-Resolved Infrared Spectroscopy

The photodissociation dynamics of CF2BrCF2I in CCl4 at 280 ± 2 K were investigated by probing the C-F stretching mode from 300 fs to 10 μs after excitation at 267 nm using time-resolved infrared spectroscopy. The excitation led to the dissociation of I or Br atoms within 300 fs, producing the CF2BrCF2 or CF2ICF2 radicals, respectively. All nascent CF2ICF2 underwent further dissociation of I, producing CF2CF2 with a time constant of 56 ± 5 ns. All nascent g-CF2BrCF2 isomerized into the more stable a-CF2BrCF2 with a time constant of 47 ± 5 ps. Furthermore, a-CF2BrCF2 underwent a bimolecular reaction with either itself (producing CF2BrCF2Br and CF2CF2) or Br in the CCl4 solution (producing CF2BrCF2Br) at a diffusion-limited rate. The secondary dissociation of Br from a-CF2BrCF2 was significantly slow to compete with the bimolecular reactions. Overall, approximately half of the excited CF2BrCF2I at 267 nm produced CF2BrCF2Br, whereas the other half produced CF2CF2. The excess energies in the nascent radicals were thermalized much faster than the secondary dissociation of I from CF2ICF2 and the observed bimolecular reactions, implying that the secondary reactions proceeded under thermal conditions. This study further demonstrates that structure-sensitive time-resolved infrared spectroscopy can be used to study various reaction dynamics in solution in real time.

СТРУКТУРА И ВНУТРИМОЛЕКУЛЯРНАЯ ПОДВИЖНОСТЬ НЕКОТОРЫХ ПРОИЗВОДНЫХ БИС(ТИО)ФОСФОРИЛИРОВАННЫХ АМИДОВ В РАСТВОРАХ CCl4, CD2Cl2 И CD3CN

The structure and intramolecular mobility of some derivatives of bis(thio)phosphorylated amides in CCl4, CD2Cl2, and CD3CN solutions were examined by 1H and 31P NMR spectroscopy. A comparative analysis of the temperature-dependent 1H and 31P NMR spectra of the studied compounds with symmetric and asymmetric substitution at phosphorus atoms was carried out. Various intramolecular processes were identified – rotation around C-N bonds, conformational transformations of molecules, tautomerism, and phosphorylotropic rearrangement with the formation of various conformational forms. It was shown that a dynamic equilibrium of several forms is reached, with the amide (phosphazo-) form having a clear advantage.

Исследование молекулярно-клеточных механизмов фиброзирования печени крыс при посттоксическом гепатозе смешанной этиологии и при применении окисленного декстрана

Introduction. The development of liver cirrhosis, regardless of etiology, is based on the process of fibrosis and structural alteration of the organ. Regulation of this process is associated with a high level of TGF-β expression and suppression of apoptosis in hepatocytes. Oxidized dextran (OD) has a high antifibrotic activity and is able to change the functional state of the phagocytic cell, thus preventing the development of fibrosis and stimulating reparative processes in organs with post-toxic hepatosis and liver cirrhosis. Aim. To study the molecular and cellular mechanisms of the effect of OD on the expression of epithelial-mesenchymal transition (EMT)-associated proteins during fibrosis and the development of liver cirrhosis in rats with post-toxic hepatosis. Materials and methods. In the experiment, 30 male Wistar rats weighing 280–320 g were used. The animals were divided into 2 groups. In group 1 rats (hepatosis), the post-toxic hepatosis was modeled by administration of a solution of CCl4 and ethyl alcohol. In rats from group 2, the post-toxic hepatosis was modeled in the same way, and OD was administered. The numerical density (Nai) of liver nonparenchymal cells expressing TGF-β (Kupffer cells, endothelial cells, fibroblasts) was calculated. The expression of E-cadherin, vimentin, SNAIL + SLUG by fibroblasts and hepatocytes was evaluated. Results. The numerical density (Nai) of hepatocytes expressing vimentin prevailed in the liver of group 1 rats (hepatosis), compared with that of group 2 animals (hepatosis + OD) on the 30th and 60th days. In animals of the 1st (hepatosis) group on the 60th day, a 3-fold lower numerical density of hepatocytes expressing E-cadherin was noted in comparison with that in rats treated with OD (group 2). In animals of the 1st (hepatosis) group on the 30th and 60th days, a 2-fold and 5-fold higher numerical density of hepatocytes expressing SNAIL + SLUG was noted in comparison with that in rats of the 2nd group. The numerical density of fibroblasts expressing vimentin prevailed in the liver of group 2 rats (hepatosis + OD), compared with that of group 1 animals (hepatosis) on day 30. In animals of the 1st (hepatosis) group on the 60th day, a 6-fold higher numerical density of fibroblasts expressing E-cadherin was noted in comparison with that in rats treated with OD (group 2). In animals of the 1st (hepatosis) group on the 30th and 60th days, the numerical density of fibroblasts expressing SNAIL + SLUG was 6 and 7 times higher than in rats treated with OD (group 2). In the liver of animals of the 2nd group (hepatosis + OD), the numerical density of cells expressing TGF-β was lower in comparison with that of animals of the 1st group (hepatosis) by 2.5 times on the 30th day and 3.6 times on the 60th day of the experiment. Conclusion. In post-toxic hepatosis, the expression of TGF-β, SNAIL + SLUG and vimentin proteins increases in liver parenchymal and nonparenchymal cells, contributing to the acquisition of a mesenchymal immunophenotype by cells, which leads to increased profibrotic activity and the development of liver cirrhosis. The use of OD in post-toxic hepatosis reduces the expression of vimentin, TGF-β and EMT-associated proteins in liver parenchymal and nonparenchymal cells, which decreases the severity of fibroplastic processes and prevents the development of liver cirrhosis.

Structural Changes in the Liver in Post-Toxic Cirrhosis and Its Treatment with Oxidized Dextran. Immunohistochemical Research

In adult Wistar rats, post-toxic liver cirrhosis was induced by intraperitoneal injection of 50% oil solution of CCl4 and peroral administration of 6.5% aqueous solution of ethyl alcohol over 60 days. Histological examination of the liver revealed vacuolar degeneration and necrosis of hepatocytes, formation of false lobules, expression of collagens I and III periportally and in interlobular spaces, ascites, and hydrothorax. Then, oxidized dextran with a molecular weight of 40 kDa (2 ml of a 5% aqueous solution) was intraperitoneally injected every fourth day over 30 days. Against the background of treatment with oxidized dextran, the volume density of collagens I and III decreased by more than 2 times, the "collagen-producing" activity of fibroblasts decreased by 47%, and the number of fibroblasts decreased, including by the mechanism of apoptosis. The decrease in the collagen content in the liver of rats treated with oxidized dextran was apparently associated with blockade of collagen assembly due to the aldehyde-aldehyde interaction of tropocollagens and oxidized dextran.