rat liver
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2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Xian Zhang ◽  
Jiajia Ge ◽  
Xuejuan Zhu ◽  
Haifeng Zhang ◽  
Yuanzi Wang ◽  
...  

The aim of the present study was to investigate the effects and mechanism of oxymatrine (OMT) combined with compound yinchen granules (CYG) on the apoptosis of hepatocytes through the Akt/FoxO3a/Bim pathway in rats with acute liver failure. The rat model of acute liver failure was established using lipopolysaccharide/D-galactosamine (LPS/D-GalN). The expression of proteins in rat liver tissues was detected by western blot analysis. The mRNA expression of FoxO3a, Bim, Bax, Bcl-2, and caspase-3 in rat liver tissues was detected by RT-qPCR. The apoptosis rate of rat hepatocytes was determined by flow cytometry. Western blots showed that when compared with the normal group, the expression of p-Akt and p-FoxO3a in the model group was decreased ( P < 0.05 ), while the expression of Bim was increased ( P < 0.01 ). Compared with the model group, the expression of p-Akt and p-FoxO3a in the OMT group and the OMT combined with CYG groups was increased ( P < 0.05 or P < 0.01 ), while the expression of Bim was decreased ( P < 0.05 ). The Bax/Bcl-2 ratio and caspase-3 protein expression in the model group were significantly higher than those in the normal group ( P < 0.01 ). The Bax/Bcl-2 ratio and the expression of caspase-3 protein in the OMT group and the OMT combined with CYG groups were significantly lower than those in the model group ( P < 0.01 ). The results of RT-qPCR were consistent with those of western blot. The results of flow cytometry showed that the apoptosis rate of hepatocytes in the OMT group and the OMT combined with CYG groups was significantly lower than that in the model group ( P < 0.05 or P < 0.01 ). We concluded that LPS/D-GalN can induce apoptosis of hepatocytes in rats with acute liver failure through the Akt/FoxO3a/Bim pathway. OMT combined with CYG inhibits apoptosis of hepatocytes in rats with acute liver failure via the Akt/FoxO3a/Bim pathway.


Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 90
Author(s):  
Jagjeet Singh ◽  
Annu Phogat ◽  
Chandra Prakash ◽  
Sunil Kumar Chhikara ◽  
Sandeep Singh ◽  
...  

Oxidative stress-mediated tissue damage is primarily involved in hepatic injuries and dysfunctioning. Natural antioxidants have been shown to exert hepatoprotective, anti-inflammatory and antiapoptotic properties. The present study evaluated the effect of N-acetylcysteine (NAC) against monocrotophos (MCP) exposure-induced toxicity in the rat liver. Albino Wistar rats were divided into four groups: (1) control, (2) NAC-treated, (3) MCP-exposure, (4) NAC and MCP-coexposure group. The dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) were administered orally for 28 days. Exposure to MCP caused a significant increase in lipid peroxidation, protein oxidation and decreased glutathione content along with the depletion of antioxidant enzyme activities. Further MCP exposure increased pro-inflammatory cytokines levels and upregulated Bax and Caspase-3 expressions. MCP exposure also caused an array of structural alternations in liver tissue, as depicted by the histological and electron microscopic analysis. Thepretreatment of NAC improved glutathione content, restored antioxidant enzyme activities, prevented oxidation of lipids and proteins, decreased pro-inflammatory cytokines levels and normalized apoptotic protein expression. Treatment of NAC also prevented histological and ultrastructural alternations. Thus, the study represents the therapeutic efficacy and antioxidant potential of NAC against MCP exposure in the rat liver.


Author(s):  
G. F. Mukhammadieva ◽  
A. B. Bakirov ◽  
D. O. Karimov ◽  
Ya. V. Valova ◽  
M. M. Ziatdinova ◽  
...  

The aim of the study was to study the effect of hepatoprotective drugs on the expression of the Sod1 gene in rats with ethanol liver damage.Materials and methods. Male outbred white rats were used in the experiment. Five groups of animals were formed, 14 individuals each. Distilled water was administered to rats of the 1st group (control); Group 2 — ethanol at a dose of 5 g/kg of body weight; Group 3 — ethanol and heptor at a dose of 72 mg/kg; Group 4 — ethanol and mexidol at a dose of 50 mg/kg; Group 5 — ethanol and OMU at a dose of 50 mg/kg. The drugs were administered 1 hour before the introduction of ethanol. 24 and 72 hours after the introduction of ethanol (7 individuals), the animals were decapitated and the liver was removed. The expression level of the Sod1 gene was assessed using real-time reverse transcription PCR.Results. The fold change in Sod1 expression in rat liver after 24 h practically did not change in response to the introduction of ethanol to the animals. A tendency to a slight decrease was observed in relation to changes in the expression of Sod1 with the use of heptor and mexidol, while under the influence of OMU, the expression level increased moderately. After 72 h, the exposure to ethanol was accompanied by a slight decrease in the frequency of expression of the Sod1 gene. A similar trend was observed with respect to changes in Sod1 expression with the use of heptor, mexidol, and OMU.Conclusion. The results obtained indicate that the introduction of both ethanol and the prophylactic use of hepatoprotective drugs did not lead to significant changes in the level of Sod1 gene expression in rat liver. Additional studies are needed to identify the mechanisms of regulation of the antioxidant system, as well as the search for drugs that affect the transcriptional activity of genes.


2021 ◽  
pp. 905-911
Author(s):  
R. Endlicher ◽  
Z. Drahota ◽  
O. Kučera ◽  
Z. Červinková

Mitochondria play an important role in the cell aging process. Changes in calcium homeostasis and/or increased reactive oxygen species (ROS) production lead to the opening of mitochondrial permeability transition pore (MPTP), depolarization of the inner mitochondrial membrane, and decrease of ATP production. Our work aimed to monitor age-related changes in the Ca2+ ion effect on MPTP and the ability of isolated rat liver mitochondria to accumulate calcium. The mitochondrial calcium retention capacity (CRC) was found to be significantly affected by the age of rats. Measurement of CRC values of the rat liver mitochondria showed two periods when 3 to17-week old rats were tested. 3-week and 17-week old rats showed lower CRC values than 7-week old animals. Similar changes were observed while testing calcium-induced swelling of rat liver mitochondria. These findings indicate that the mitochondrial energy production system is more resistant to calcium-induced MPTP opening accompanied by the damaging effect of ROS in adult rats than in young and aged animals.


2021 ◽  
Vol 31 (3) ◽  
pp. 0-0
Author(s):  
Zehra Bedir ◽  
Kezban Tuna Ozkaloglu Erdem ◽  
Irem Ates ◽  
Tulat Ceren Olmezturk Karakurt ◽  
Cebrail Gursul ◽  
...  

Author(s):  
Marina R. Sartori ◽  
Claudia D.C. Navarro ◽  
Roger F. Castilho ◽  
Anibal E. Vercesi

The interaction between supraphysiological cytosolic Ca2+ levels and mitochondrial redox imbalance mediates the mitochondrial permeability transition (MPT). MPT is involved in cell death, diseases, and aging. This study compared the liver mitochondrial Ca2+ retention capacity and oxygen consumption in the long-lived red-footed tortoise (Chelonoidis carbonaria) to the rat as a reference standard. Mitochondrial Ca2+ retention capacity, a quantitative measure of MPT sensitivity, was remarkably higher in tortoises than rats. This difference was minimized in the presence of the MPT inhibitors, ADP and cyclosporine A. However, the Ca2+ retention capacities of tortoise and rat liver mitochondria were similar when both MPT inhibitors were present simultaneously. NADH-linked phosphorylating respiration rates of tortoise liver mitochondria represented only 30% of the maximal electron transport system capacity, indicating a limitation imposed by the phosphorylation system. These results suggested underlying differences in putative MPT structural components (e.g. ATP synthase, adenine nucleotide translocase (ANT), and cyclophilin D) between tortoises and rats. Indeed, in tortoise mitochondria, titrations of inhibitors of the oxidative phosphorylation components revealed a higher limitation of ANT. Furthermore, cyclophilin D activity was approximately 70% lower in tortoises than in rats. Investigation of critical properties of mitochondrial redox control that affect MPT demonstrated that tortoise and rat liver mitochondria exhibited similar rates of H2O2 release and glutathione redox status. Overall, our findings suggest that constraints imposed by ANT and cyclophilin D, putative components or regulators of the MPT pore, are associated with the enhanced resistance to Ca2+-induced MPT in tortoises.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Agnieszka Ścibior ◽  
Iwona Wojda ◽  
Ewa Wnuk ◽  
Łukasz Pietrzyk ◽  
Zbigniew Plewa

Oxidative stress (OS) is a mechanism underlying metal-induced toxicity. As a redox-active element, vanadium (V) can act as a strong prooxidant and generate OS at certain levels. It can also attenuate the antioxidant barrier and intensify lipid peroxidation (LPO). The prooxidant potential of V reflected in enhanced LPO, demonstrated by us previously in the rat liver, prompted us to analyze the response of the nuclear factor erythroid-derived 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2-Keap1) system involved in cellular regulation of OS to administration of sodium metavanadate (SMV, 0.125 mg V/mL) and/or magnesium sulfate (MS, 0.06 mg Mg/mL). The levels of some Nrf2-dependent cytoprotective and detoxifying proteins, i.e., glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glutamate cysteine ligase catalytic subunit (GCLC), glutathione synthetase (GSS), NAD(P) H dehydrogenase quinone 1 (NQO1), UDP-glucumno-syltransferase 1 (UGT1), and heme oxygenase 1 (HO-1); glutathione (GSH); metallothionein (MT1); and glutamate-cysteine ligase (GCL) mRNA were measured. We also focused on the V-Mg interactive effects and trends toward interactive action as well as relationships between the examined indices. The elevated levels of Nrf2, GCL mRNA, and GCL catalytic subunit (GCLC) confirm OS in response to SMV and point to the capacity to synthesize GSH. The results also suggest a limitation of the second step in GSH synthesis reflected by the unchanged glutathione synthetase (GSS) and GSH levels. The positive correlations between certain cytoprotective/detoxifying proteins (which showed increasing trends during the SMV and/or MS administration, compared to the control) and between them and malondialdehyde (MDA), the hepatic V concentration/total content, and/or V dose (discussed by us previously) point to cooperation between the components of antioxidant defense in the conditions of the hepatic V accumulation and SMV-induced LPO intensification. The V-Mg interactive effect and trend are involved in changes in Nrf2 and UGT1, respectively. The p62 protein has to be determined in the context of potential inhibition of degradation of Keap1, which showed a visible upward trend, in comparison with the control. The impact of Mg on MT1 deserves further exploration.


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