scholarly journals Antifibrotic Effect of Lactulose on a Methotrexate-Induced Liver Injury Model

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Banu Taskin ◽  
Mümin Alper Erdoğan ◽  
Gürkan Yiğittürk ◽  
Damla Günenç ◽  
Oytun Erbaş
Keyword(s):  
Liver Injury ◽  
Rat Model ◽  
Liver Tissue ◽  
Intestinal Microbiome ◽  
Male Rats ◽  
Severe Side Effect ◽  
Tissue Samples ◽  
Injury Model ◽  
Group 2 ◽  
The Impact

The most severe side effect of prolonged MTX treatment is hepatotoxicity. The aim of this study is to investigate the effect of lactulose treatment on MTX-induced hepatotoxicity in a rat model. Twenty-four male rats were included in the study. Sixteen rats were given a single dose of 20 mg/kg MTX to induce liver injury. Eight rats were given no drugs. 16 MTX-given rats were divided into two equal groups. Group 1 subjects were given lactulose 5 g/kg/day, and group 2 subjects were given saline 1 ml/kg/day for 10 days. The rats were then sacrificed to harvest blood and liver tissue samples in order to determine blood and tissue MDA, serum ALT, plasma TNF-α, TGF-β, and PTX3 levels. Histological specimens were examined via light microscopy. Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by relatively worse histopathological scores and increased biochemical marker levels. Lactulose treatment significantly reduced the liver enzyme ALT, plasma TNF-α, TGF-β, PTX3, and MDA levels and also decreased histological changes in the liver tissue with MTX-induced hepatotoxicity in the rat model. We suggest that lactulose has anti-inflammatory and antifibrotic effects on an MTX-induced liver injury model. These effects can be due to the impact of intestinal microbiome.

scholarly journals An Experimental Study: Benefits of Digoxin on Hepatotoxicity Induced by Methotrexate Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Banu Taskin ◽  
Mümin Alper Erdoğan ◽  
Gürkan Yiğittürk ◽  
Sibel Alper ◽  
Oytun Erbaş
Keyword(s):  
Rat Model ◽  
Liver Tissue ◽  
Liver Toxicity ◽  
Male Rats ◽  
Control Group ◽  
Therapeutic Effects ◽  
Tissue Samples ◽  
Liver Model ◽  
Tnf Α ◽  
Group 2

Purpose. The aim of the study is to examine the possible therapeutic effects of a known cardiac glycoside, digoxin, on a rat model of MTX-induced hepatotoxicity. Methods. The study was conducted on twenty-four male rats. While eighteen rats received a single dose of 20 mg/kg MTX to obtain an injured liver model, six rats constituted the control group. Also, the eighteen liver toxicity model created rats were equally divided into two groups, one of which received digoxin 0.1 mg/kg/day digoxin (Group 1) and the other group (Group 2) was given saline (% 0.9NaCl) with a dose of 1 ml/kg/day for ten days. Following the trial, the rats were sacrificed to harvest blood and liver tissue samples to determine blood and tissue MDA, serum ALT, plasma TNF-α, TGF-β, IL-6, IL-1-Beta, and PTX3 levels. Results. MTX’s structural and functional hepatotoxicity was observable and evidenced by relatively worse histopathological scores and increased biochemical marker levels. Digoxin treatment significantly reduced the liver enzyme ALT, plasma TNF-α, TGF-β, PTX3, and MDA levels and decreased histological changes in the liver tissue with MTX-induced hepatotoxicity in the rat model. Conclusion. We suggest that digoxin has an anti-inflammatory and antihepatotoxic effect on the MTX-induced liver injury model.

scholarly journals Morphological Changes in the Hepatic Tissue at the Impact of Industrial Copper-bearing Dust in the Experiment

2020 ◽  
Vol 8 (E) ◽  
pp. 653-656
Author(s):  
Khamida R. Abdikadirova ◽  
Kymbat Ye. Amreyeva ◽  
Saule B. Zhautikova ◽  
Olga A. Kostyleva ◽  
Fatima S. Abikenova ◽  
...  
Keyword(s):  
Liver Tissue ◽  
Morphological Changes ◽  
White Male ◽  
Male Rats ◽  
Hepatic Tissue ◽  
Control Group ◽  
Cu Content ◽  
Group 2 ◽  
The Impact ◽  
Dual Core

BACKGROUND: It is known that an increased intake of copper (Cu) has an adverse effect, and above all leads to the defeat of parenchymal organs, including liver tissue. AIM: This study the morphological changes in the hepatic tissue at the impact of polymetallic Cu dust. METHODS: An experimental study was carried out on the outbred white male rats. Dust was injected once intratracheally at a dose of 50 mg. For dynamic observation, the animals were killed in 1, 3, and 6 months with the control group using instant decapitation. The Balkhash industrial polymetallic dust with a predominant Cu content (Cu-0.6%) was used for the study. Morphological changes were assessed using histological and morphometric methods. RESULTS: Morphometric examination of liver tissue at 30 days showed Vv necrosis increasing in 320 times in Group 2 (p < 0.001), Vv infiltrates – in 121 times (p < 0.001), Vv dystrophic altered hepatocytes – in 19.91 times (p < 0.001), Vv dual-core cells – in 23 times (p < 0.01), and Vv fibrosis – in 2.82 times (p < 0.001) in comparison with Group 1. Vv portal tracts are not reliably changed. In 90 days, there were also the following morphometric parameters increasing in comparison with the control group: Vv necrosis – in 522 times (p < 0.001), Vv infiltrates – in 395 times (p < 0.001), Vv dystrophic altered hepatocytes – in 26.7 times (p < 0.001), Vv dual-core cells – in 314 times (p < 0.01), and Vv fibrosis – in 13.27 times (p < 0.001). On the 180 day of the experiment, there was the increasing of Vv infiltrates in 421 times (p < 0.001), Vv dystrophic altered hepatocytes – in 34.09 times (p < 0.001), Vv dual-core cells – in 411 times (p < 0.001), and Vv fibrosis – in 54.09 times (p < 0.001) CONCLUSION: The impact of polymetallic dust with 0.6% Cu concentration at the early stages leads to the changes in the liver in the form of reactive hepatitis with the following transformation into portal-type hepatitis.

scholarly journals On the Impact of Nonalcoholic Fatty Liver Disease, Confirmed by Biopsy, on the Results of the Two-Dimensional Shear Elastography

2017 ◽  
pp. 88-95
Author(s):  
A. N. Katrich ◽  
A. V. Okhotina ◽  
O. N. Ponkina ◽  
N. S. Ryabin
Keyword(s):  
Shear Wave ◽  
Liver Tissue ◽  
Liver Stiffness ◽  
Shear Wave Elastography ◽  
Liver Parenchyma ◽  
Outcome Analysis ◽  
Diagnostic Efficiency ◽  
Nonalcoholic Fatty Liver ◽  
Group 2 ◽  
The Impact

The aim:to study of the effect of NAFLD on the results of shear elastography (based on the results of liver biopsy).  Materials and methods.We have performed outcome analysis in 137 patients, treated from 2015 to 2016. All patients had chronic diffuse liver diseases and were hospitalized for morphological evaluation and diagnosis clarification. Group 1 (n = 117) with no fat changes in the liver parenchyma. Group 2 (n = 20) with steatosis of the liver.  In our work, we used: scanner Aixplorer (France). All patients underwent shear wave elastography (2DSWE) with the study of the quantitative index of stiffness of liver tissue, staging the results on the Metavir scale.Results.In the 1st group of patients (without steatosis), in the ROC analysis, cutoff values of elasticity were obtained, the diagnostic efficiency of the Metavir stage of fibrosis was the most optimal: for F2 > 6.8 kPa (sensitivity 85.7, specificity 52, 9, AUROC 0.684); For F3 > 8.5 kPa (sensitivity 91, specificity 57.1, AUROC 0.745); For F4 > 14 kPa (sensitivity 95.7, specificity 52.2, AUROC 0.791). It was found, that the presence of steatosis significantly increases the elasticity of the liver tissue. So, in the subgroup sF0 (with steatosis) was a significant increasing of young's module Ме = 11,2 kPa (95% CI 7,3–17,5) compared to Ме = 6,1 kPa (95% CI 5,4– 9,6) in the subgroup F0 (without steatosis) (P = 0,0168, AUROC = 0,741) and up to Ме=9,95 kPa (95% CI 6,8–13,0) in the subgroup sF0 + sF1 (with steatosis) compared with Ме=6,65 kPa (95%CI 5,6–9,5) of the subgroup F0 + F1 (without steatosis) (P = 0.0295, = 0.707). This increase was, respectively, 83,6% and 49.6%  Сonclusions.This study confirmed the effectiveness of the shear wave elastography method in assessing the relationship between stiffness parameters and the morphological fibrosis of the liver parenchyma and also contributed to the final confirmation of the effect of steatosis on  liver stiffness.

scholarly journals Protective Role of Ce Nanoparticles Against the Hepatotoxicity Induced by Exposure to Paraquat

2018 ◽  
Vol 6 (2) ◽  
pp. 37-43
Author(s):  
Hamid Heidary Dartoti ◽  
Farzin Firozian ◽  
Sara Soleimani Asl ◽  
Akram Ranjbar
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Protective Role ◽  
Male Rats ◽  
Hepatic Tissue ◽  
Control Group ◽  
Serum Samples ◽  
Tissue Samples ◽  
Total Antioxidant ◽  
Group 2

Objectives: The present study aimed to investigate the antioxidant activity of cerium oxide nanoparticles (CeNPs) against paraquat (PQ)-induced liver injury in rats. Methods: Thirty-two male rats were divided into four 8-member groups and treated intraperitoneally with PQ and/or CeNPs for 14 days. Group 1 received PQ (5 mg/kg/d), group 2 received CeNPs (15, 30, and 60 mg/kg/d), group 3 received a combination of PQ (5 mg/kg/d) and CeNPs (15, 30, and 60 mg/kg/d), and group 4 (control group) received saline solution. Serum samples along with liver tissue samples were collected from all the rats. Oxidative stress (OS) biomarkers including total antioxidant capacity, lipid peroxidation, total thiol groups, DNA damage, and nitric oxide levels were determined. Histological samples were also analyzed using hematoxylin and eosin staining slides. Results: Levels of oxidative stress and hepatic tissue damage were significantly higher in the PQ group compared to the control group. CeNPs at a dose of 15 mg/kg showed the antioxidant activity and compromised the PQ-induced damage. Conclusion: In the scenario tested in this study, CeNPs could reduce the levels of OS, as well as hepatic damage induced by PQ.

scholarly journals Development and Validation of a Highly Sensitive LC-MS/MS Method for the Analysis of Bile Acids in Serum, Plasma, and Liver Tissue Samples

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 282
Author(s):  
Cristina Gómez ◽  
Simon Stücheli ◽  
Denise V. Kratschmar ◽  
Jamal Bouitbir ◽  
Alex Odermatt
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Bile Acids ◽  
Liver Tissue ◽  
Bioactive Molecules ◽  
Rodent Species ◽  
Drug Induced ◽  
Tissue Samples ◽  
Drug Induced Liver Injury ◽  
Bile Acid Profiles

Bile acids control lipid homeostasis by regulating uptake from food and excretion. Additionally, bile acids are bioactive molecules acting through receptors and modulating various physiological processes. Impaired bile acid homeostasis is associated with several diseases and drug-induced liver injury. Individual bile acids may serve as disease and drug toxicity biomarkers, with a great demand for improved bile acid quantification methods. We developed, optimized, and validated an LC-MS/MS method for quantification of 36 bile acids in serum, plasma, and liver tissue samples. The simultaneous quantification of important free and taurine- and glycine-conjugated bile acids of human and rodent species has been achieved using a simple workflow. The method was applied to a mouse model of statin-induced myotoxicity to assess a possible role of bile acids. Treatment of mice for three weeks with 5, 10, and 25 mg/kg/d simvastatin, causing adverse skeletal muscle effects, did not alter plasma and liver tissue bile acid profiles, indicating that bile acids are not involved in statin-induced myotoxicity. In conclusion, the established LC-MS/MS method enables uncomplicated sample preparation and quantification of key bile acids in serum, plasma, and liver tissue of human and rodent species to facilitate future studies of disease mechanisms and drug-induced liver injury.

Androstenediol administration after trauma-hemorrhage attenuates inflammatory response, reduces organ damage, and improves survival following sepsis

2006 ◽  
Vol 291 (2) ◽  
pp. G260-G266 ◽  
Author(s):  
László Szalay ◽  
Tomoharu Shimizu ◽  
Takao Suzuki ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Cell Activation ◽  
Cecal Ligation ◽  
Male Rats ◽  
Sham Operation ◽  
Protective Effects ◽  
Tissue Samples ◽  
Septic Complications ◽  
Neutrophil Cell

Although androstenediol (adiol or 5-androstene-3β,17β-diol), a metabolite of dehydroepiandrosterone (DHEA), has protective effects following trauma-hemorrhage (T-H), it remains unknown whether administration of adiol has any salutary effects on the inflammatory response and outcome following a combined insult of T-H and sepsis. Male rats underwent T-H shock [mean arterial pressure (MAP) 40 mmHg for 90 min] followed by resuscitation. Adiol (1 mg/kg body wt) or vehicle was administered at the end of resuscitation. Sepsis was induced by cecal ligation and puncture (CLP) at 20 h after T-H or sham operation. Five hours after CLP, plasma and tissue samples were analyzed for cytokines (IL-6 and IL-10), MPO, neutrophil chemotactic factor (CINC-3), and liver injury (alanine aminotransferase and lactate dehydrogenase). In another group of rats, the gangrenous cecum was removed at 10 h after CLP, the cavity was irrigated with warm saline and closed in layers, and mortality was recorded over 10 days. T-H followed by CLP produced a significant elevation in plasma IL-6 and IL-10 levels, enhanced neutrophil cell activation, and resulted in liver injury. Adiol administration prevented the increase in cytokine production, neutrophil cell activation, and attenuated liver injury. Moreover, rats subjected to the combined insult, receiving vehicle or adiol, had a 50% and 6% mortality, respectively. Since adiol administration suppresses proinflammatory cytokines, reduces liver damage, and decreases mortality after the combined insult of T-H and sepsis, this agent appears to be a novel adjunct to fluid resuscitation for decreasing T-H-induced septic complications and mortality.

scholarly journals The Use of Photodynamic Therapy on Medication-Related Osteonecrosis of the Jaws: An Animal Study

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Gökay Karapınar ◽  
Özge Özdal Zincir ◽  
Meral Ünür ◽  
Necat Vakur Olgaç
Keyword(s):  
Photodynamic Therapy ◽  
Osteonecrosis Of The Jaw ◽  
Male Rats ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Osteonecrosis Of The Jaws ◽  
Tracp 5B ◽  
Valuable Marker ◽  
Group 3 ◽  
Group 2

SummaryBackground/Aim: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) was first introduced in 2003 and its scope was expanded by the name medication-related osteonecrosis of the jaw (MRONJ), since 2014. This study aimed to evaluate the effects of photodynamic therapy (FDT) on tissue samples by histopathological and histomorphometric examination and serum TRACP-5b (Tartrateresistant acid phosphatase-5b) measurement in rats.Material and Methods: 24 Sprague-Dawley male rats were divided into 3 groups comprising 8 animals. Zoledronic acid was administered to groups 1 and 2 and 0.9% sodium chloride was administered to group 3 intraperitoneally. After the injections were completed, dental extractions were performed. Photodynamic therapy was applied to group 2, three times a weekfor the two weeks after the extraction. In the 16th week, sacrification was performed. Rats were undergone histopathologic and histomorphometric evaluations.Results: Photodynamic therapy has led to a decrease in epithelial opening and inflammation and an increase in the formation of new bone. Serum TRACP-5b values were shown to decrease significantly in the presence of osteonecrosis.Conclusions: PDT was shown to be useful in reducing MRONJ risk in rats. As a serum biomarker, Serum TRACP-5b could be a valuable marker. Additional studies should confirm the findings.

scholarly journals Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Mei-Ying Huang ◽  
Dian-Wei Wan ◽  
Jie Deng ◽  
Wen-Jie Guo ◽  
Yue Huang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Acute Liver Injury ◽  
Recovery Process ◽  
Regulatory Relationship ◽  
Negative Feedback Regulation ◽  
Injury Model ◽  
The Impact

Background. Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods. In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results. TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression ( p < 0.05 ) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress ( p < 0.05 ). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers ( p < 0.05 ). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions. Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

scholarly journals The impact of ademetionine and ipidacrine/phenibut on the NCAM distribution and behavior in the rat model of drug-induced liver injury

2020 ◽  
Vol 18 (3) ◽  
pp. 155-164
Author(s):  
Diana Muraviova ◽  
◽  
Yuliia Kharchenko ◽  
Kateryna Pierzynowska ◽  
Stefan Pierzynowski ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Injury ◽  
Field Test ◽  
Liver Damage ◽  
Rat Model ◽  
Open Field Test ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
The Impact ◽  
The Brain

Introduction. Recently, more attention is being paid to the drug-induced liver injury (DILI) as a consequence of the tuberculos is treatment and the need for new medicine is emphasized. The use of isoniazid and rifampicin has a potentiating effect, which increases the risk of substancial liver damage. In turn, systemic accumulation of toxic metabolites leads to negative changes in various organs, including the brain. It causes an imbalance in biochemical and neurophysiological processes in the brain, ultimately giving the onset to the development of hepatic encephalopathy. Aim. The effects of rifampicin and isoniazid on the central nervous system have not been studied before and we aimed to evaluate the impact these two substances have on the neuronal cell adhesion molecules (NCAM) distribution and animal behavior in the rat model of DILI. Material and methods. The 24 male Wistar rats, weighing 180-220 g were used for the experiment and divided to the groups (n=6): 1 – control; 2 – rats with experimental DILI; 3 – rats with DILI plus the intravenous infusion of S-adenosyl-L-methionine at a dose of 35 mg/kg; 4 – rats with DILI plus a fixed combination of ipidacrine hydrochloride at a dose 1 mg/kg body weight and phenibut at a dose 60 mg/kg body weight daily for the last 14 days of the experiment. All experimental procedures were carried out in the accordance with the principles outlined in the current Guide to the Care and Use of Experimental Animals. The locomotor and research activities were studied in the open field test. The activity of aspartate aminotransferase (AST, ЕС 2.6.1.1) and alanine aminotransferase (ALT, ЕС 2.6.1.2) in the serum of rats were tested to confirm the liver damage. The quantitative analyses of soluble and membrane forms of NCAM were performed with ELISA. The ANOVA followed by a Tukey post-hoc test was used to assess statistical differences between groups. Results. Our investigation in the open field test revealed a significant decrease in the locomotor and research activity of rats after 28 days of rifampicin and isoniazid administration. The recovery of investigated parameters was observed in groups of animals treated with ademetionine (AD group) or combination of ipidacrine and phenibut (IP/PB group). We also observed that changes in rats’ behavior were consistent with alterations of the NCAM levels in the thalamus and hippocampus. Thus, the level of membrane NCAM was significantly decreased under DILI in both investigated brain regions (thalamus and hippocampus), while both AD and IP/PB treatments restored membrane NCAM levels towards those observed in the control group at least in the hippocampus. Conclusion. Obtained data suggests that both ademetionine and combinated drug containing ipidacrine and phenibut possesses neuroprotective properties and could prevent the decline in synaptic plasticity under antitubercular therapy.

scholarly journals Dexmedetomidine attenuates lipopolysaccharide-induced acute liver injury in rats by inhibiting caveolin-1 downstream signaling pathway

2021 ◽  
Vol 41 (3) ◽  
Author(s):  
Fei Tong ◽  
Wenchao Shen ◽  
Pengtao Song ◽  
Jiafeng Song ◽  
Yonghe Hu ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Liver Tissue ◽  
Acute Liver Injury ◽  
Male Rats ◽  
Tissue Homogenate ◽  
Caveolin 1 ◽  
Significant Difference ◽  
Group D

Abstract Objective: The aim of the present study is to investigate the anti-injury and anti-inflammatory effects of dexmedetomidine (Dex) in acute liver injury induced by lipopolysaccharide (LPS) in Sprague–Dawley rats and its possible mechanism. Methods: The acute liver injury model of male rats was established by injecting LPS into tail vein. The mean arterial pressure (MAP) of rats was recorded at 0–7 h, and lactic acid was detected at different time points. Wet/dry weight ratio (W/D) was calculated. Pathological changes of rat liver were observed by HE staining. ALT and AST levels in serum were detected. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) in liver tissue homogenate and the levels of IL-1β and IL-18 in serum were detected by ELISA. Protein levels of Caveolin-1 (Cav-1), TLR-4 and NLRP3 in liver tissue were tested by immunohistochemistry method. The expression of Cav-1, TLR-4 and NLRP3 mRNA in liver tissue was detected by quantitative polymerase chain reaction (qPCR) to explore its related mechanism. Results: Compared with NS group, serum lactic acid, W/D of liver tissue, MPO, SOD, IL-1β and IL-18 were significantly increased and MAP decreased significantly in LPS group and D+L group. However, compared with NS group, D group showed no significant difference in various indicators. Compared with LPS group, MPO, SOD, IL-1β and IL-18 were significantly decreased and MAP was significantly increased in D+L group. D+L group could significantly increase the level of Cav-1 protein and decrease the level of TLR-4 and NLRP3 protein in liver tissue caused by sepsis. The expression of Cav-1 mRNA was significantly up-regulated and the expression of TLR-4 and NLRP3 mRNA was inhibited in D+L group. Conclusion: Dex pretreatment protects against LPS-induced actue liver injury via inhibiting the activation of the NLRP3 signaling pathway by up-regulating the expression of Cav-1 by sepsis.

Sign in / Sign up

Export Citation Format

Share Document