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1.
Int J Mol Sci ; 24(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37629192

RESUMO

PTSD is associated with disturbed hepatic morphology and metabolism. Neuronal mitochondrial dysfunction is considered a subcellular determinant of PTSD, but a link between hepatic mitochondrial dysfunction and hepatic damage in PTSD has not been demonstrated. Thus, the effects of experimental PTSD on the livers of high anxiety (HA) and low anxiety (LA) rats were compared, and mitochondrial determinants underlying the difference in their hepatic damage were investigated. Rats were exposed to predator stress for 10 days. Then, 14 days post-stress, the rats were evaluated with an elevated plus maze and assigned to HA and LA groups according to their anxiety index. Experimental PTSD caused dystrophic changes in hepatocytes of HA rats and hepatocellular damage evident by increased plasma ALT and AST activities. Mitochondrial dysfunction was evident as a predominance of small-size mitochondria in HA rats, which was positively correlated with anxiety index, activities of plasma transaminases, hepatic lipids, and negatively correlated with hepatic glycogen. In contrast, LA rats had a predominance of medium-sized mitochondria. Thus, we show links between mitochondrial dysfunction, hepatic damage, and heightened anxiety in PTSD rats. These results will provide a foundation for future research on the role of hepatic dysfunction in PTSD pathogenesis.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Animais , Ratos , Transtornos de Ansiedade , Ansiedade/etiologia , Fígado , Mitocôndrias
2.
Biomedicines ; 11(4)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37189753

RESUMO

A study of the morphofunctional condition of mice with transplantable melanoma B16 under the influence of a normal daylight regime, constant lighting and constant darkness was conducted. It was shown that exposure to constant lighting leads to intensification of the proliferation of melanoma cells, more significant growth and spread of the tumor, the development of more pronounced secondary changes, the presence of perivascular growth and an increase in perineural invasion. At the same time, keeping of animals in constant darkness significantly reduced the intensity of the proliferative process in the tumor and lead to tumor regression in the absence of signs of lympho-, intravascular and intraneural invasion. Intergroup differences in tumor cell status were confirmed by the results of micromorphometric studies. It was also shown that the expression of clock genes was suppressed by an exposure to constant light, while an influence of constant darkness, on contrary, led to its intensification.

3.
J Bioenerg Biomembr ; 55(2): 93-101, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36884199

RESUMO

Pentaamino acid fullerene C60 derivative is a promising nanomaterial, which exhibited antihyperglycemic activity in high-fat diet and streptozotocin-induced diabetic rats. This study investigates the effect of pentaaminoacid C60 derivative (PFD) in rats with metabolic disorders. Rats were assigned to 3 groups (of 10 rats each) as follows: Group 1 (normal control), group 2 included the protamine-sulfate-treated rats (the untreated group of animals with the model metabolic disorder); group 3 (Protamine sulfate + PFD) included the protamine-sulfate-treated model rats that received an intraperitoneal injection of PFD. Metabolic disorder in rats was initiated by protamine sulfate (PS) administration. The PS + PFD group was injected intraperitoneally with PFD solution (3 mg/kg). Protamine sulfate induces biochemical changes (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) in the blood and morphological lesions in rat liver and pancreas. The potassium salt of fullerenylpenta-N-dihydroxytyrosine in protamine sulfate-induced rats normalized blood glucose level and the serum lipid profile and improved hepatic function markers. Treatment with PFD restored pancreas islets and liver structure of protamine sulfate-induced rats compared to the untreated group. PFD is a promising compound for further study as a drug against metabolic disorders.


Assuntos
Diabetes Mellitus Experimental , Fulerenos , Ratos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Fulerenos/farmacologia , Fulerenos/uso terapêutico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Protaminas/farmacologia , Protaminas/uso terapêutico , Sulfatos/uso terapêutico
4.
Int J Mol Sci ; 23(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36142658

RESUMO

A separate and combined effect of constant illumination and chronic alcohol intoxication (CAI) on diurnal dynamics of micromorphometric parameters of hepatocytes in female Wistar rats and p53, Ki-67, PER2, BMAL1, and ADH5 expression in these cells were studied. The increase in apoptotic activity and proliferation in all animals under the action of chronodestructors is shown. All experimental animals showed a decrease in BMAL1 expression and increase in PER2 expression; ADH5 is overexpressed under the influence of ethanol. Circadian rhythms (CRs) of BMAL1, PER2, p53, and Ki-67 expression persist in all groups, except combined action of chronodestructors, and ADH5 CRs persist in all groups-thus, these rhythms in females are quite stable. CRs of the hepatocyte nuclei area are preserved in all the studied groups, although they undergo a significant shift. At the same time, the CRs of the hepatocyte area are destroyed under the action of light, both independently and in combination with CAI, and the CR of the nuclear-cytoplasmic ratio (NCR) is destroyed by exposure to CAI. It can be assumed that CRs of the hepatocyte area are significantly affected by dark deprivation and NCR rhythm is sensitive to ethanol consumption, while the stability of studied genes' expression rhythms at separate influences of studied chronodestructors is maintained by yet unknown adaptation mechanisms. It is necessary to note that, according to our previous studies of male rats, rat females show significantly greater stability of the studied CRs.


Assuntos
Intoxicação Alcoólica , Alcoolismo , Fatores de Transcrição ARNTL/metabolismo , Intoxicação Alcoólica/metabolismo , Alcoolismo/metabolismo , Animais , Ritmo Circadiano , Etanol/farmacologia , Feminino , Antígeno Ki-67/metabolismo , Iluminação , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/metabolismo
5.
Environ Sci Pollut Res Int ; 29(55): 83686-83697, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35771326

RESUMO

Light pollution has become a serious problem in many urbanized areas of the world. The impact of prolonged exposure to light and consequent disruption of natural circadian rhythms has significant health implications. The current study was undertaken to evaluate the effect of prolonged exposure to light, simulating urban light pollution, on liver health. In order to evaluate the effect of prolonged exposure to light, we examined the morphofunctional state, immunohistochemical and micromorphometric parameters of rat liver in normal conditions and following prolonged lighting exposure. Our results show that nocturnal light disruption triggers a cell death in the liver within 3 weeks (necrosis and apoptosis of hepatocytes) and stimulates a change in normal cellular karyometric parameters. At the same time, intracellular regeneration takes place within the organ, which manifests through hepatocyte hypertrophy. Under the influence of constant illumination, the circadian rhythms (CRs) of the size of hepatocytes and their nuclei are restructured, and the rhythm of the nuclear-cytoplasmic ratio is destroyed. The destruction of the CR of expression of p53 and Ki-67 also occurs against the background of the rearrangement of the daily rhythmicity of Per2 and Bmal1. The revealed changes in the morphofunctional state of the liver under the influence of light pollution indicate that a violation of normal illumination regimes is a potent factor leading to significant structural changes in the liver.


Assuntos
Raio , Animais , Ratos , Ritmo Circadiano , Fígado/fisiologia
6.
Molecules ; 27(3)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35164026

RESUMO

Chlorophytum genus has been extensively studied due to its diverse biological activities. We evaluated the methanolic extract of leaves of Chlorophytum comosum (Green type) (Thunb.) Jacques, the species that is less studied compared to C. borivilianum. The aim was to identify phytoconstituents of the methanolic extract of leaves of C. comosum and biological properties of its different fractions. Water fraction was analyzed with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Nineteen compounds belonging to different chemical classes were identified in the methanolic extract of leaves of C. comosum (Green type) (Thunb.) Jacques. In addition to several fatty acids, isoprenoid and steroid compounds were found among the most abundant constituents. One of the identified compounds, 4'-methylphenyl-1C-sulfonyl-ß-d-galactoside, was not detected earlier in Chlorophytum extracts. The water fraction was toxic to HeLa cells but not to Vero cells. Our data demonstrate that methanolic extract of leaves of C. comosum can be a valuable source of bioactive constituents. The water fraction of the extract exhibited promising antitumor potential based on a high ratio of HeLa vs. Vero cytotoxicity.


Assuntos
Asparagaceae/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Chlorocebus aethiops , Cromatografia Gasosa-Espectrometria de Massas , Células HeLa , Humanos , Metanol/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Folhas de Planta/química , Testes de Toxicidade , Células Vero
7.
Int J Mol Sci ; 22(23)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34884810

RESUMO

A study of the influence of chronic alcohol intoxication, constant illumination and their combined effects on the morphofunctional state of the rat liver and the circadian rhythms (CR) of the studied parameters of the organism was carried out. It was found that both alcohol and constant illumination caused significant changes in the structure of the liver, as well as in the circadian rhythmicity of micromorphometric parameters of hepatocytes, ALT, and total and direct bilirubin rhythms; however, the combined effects of ethanol and constant illumination had the most significant effect on the studied parameters of the organism. These two factors caused disturbances in the circadian rhythms of the micromorphometric parameters of hepatocytes, disruption of the circadian rhythms of total protein, albumin, AST, ALT, and direct and total bilirubin, as well as disturbances in the expression and rhythmicity of the studied clock genes against a background of the development of an inflammatory process in the liver.


Assuntos
Alcoolismo/patologia , Ritmo Circadiano/fisiologia , Etanol/toxicidade , Iluminação/efeitos adversos , Fígado/patologia , Intoxicação Alcoólica/patologia , Animais , Bilirrubina/análise , Hepatócitos/patologia , Hepatopatias Alcoólicas/patologia , Masculino , Ratos , Ratos Wistar
8.
FEBS Lett ; 582(2): 238-42, 2008 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-18083123

RESUMO

Photosynthetic reaction centers of Blastochloris viridis require two quanta of light to catalyse a two-step reduction of their secondary ubiquinone Q(B) to ubiquinol. We employed capacitive potentiometry to follow the voltage changes that were caused by the accompanying transmembrane proton displacements. At pH 7.5 and 20 degrees C, the Q(B)-related voltage generation after the first flash was contributed by a fast, temperature-independent component with a time constant of approximately 30 micros and a slower component of approximately 200 micros with activation energy (E(a)) of 50 kJ/mol. The kinetics after the second flash featured temperature-independent components of 5 micros and 200 micros followed by a component of 600 micros with E(a) approximately 60 kJ/mol.


Assuntos
Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo , Prótons , Rodopseudomonas/metabolismo , Catálise , Cinética , Complexo de Proteínas do Centro de Reação Fotossintética/química
9.
Biophys J ; 86(6): 4094-109, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15189903

RESUMO

The membrane portion of F(0)F(1)-ATP synthase, F(0), translocates protons by a rotary mechanism. Proton conduction by F(0) was studied in chromatophores of the photosynthetic bacterium Rhodobacter capsulatus. The discharge of a light-induced voltage jump was monitored by electrochromic absorption transients to yield the unitary conductance of F(0). The current-voltage relationship of F(0) was linear from 7 to 70 mV. The current was extremely proton-specific (>10(7)) and varied only slightly ( approximately threefold) from pH 6 to 10. The maximum conductance was approximately 10 fS at pH 8, equivalent to 6240 H(+) s(-1) at 100-mV driving force, which is an order-of-magnitude greater than of coupled F(0)F(1). There was no voltage-gating of F(0) even at low voltage, and proton translocation could be driven by deltapH alone, without voltage. The reported voltage gating in F(0)F(1) is thus attributable to the interaction of F(0) with F(1) but not to F(0) proper. We simulated proton conduction by a minimal rotary model including the rotating c-ring and two relay groups mediating proton exchange between the ring and the respective membrane surface. The data fit attributed pK values of approximately 6 and approximately 10 to these relays, and placed them close to the membrane/electrolyte interface.


Assuntos
Complexos de ATP Sintetase/metabolismo , Cromatóforos/enzimologia , Ativação do Canal Iônico/fisiologia , Prótons , Rhodobacter capsulatus/enzimologia , Citocromos/metabolismo , Gramicidina/metabolismo , Concentração de Íons de Hidrogênio , Modelos Teóricos , Osmose/fisiologia , Espectrofotometria
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