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 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 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 Platelet-Rich Plasma Ameliorates Monosodium Iodoacetate-Induced Ankle Osteoarthritis in the Rat Model via Suppression of Inflammation and Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
G. H. Ragab ◽  
F. M. Halfaya ◽  
O. M. Ahmed ◽  
W. Abou El-Kheir ◽  
E. A. Mahdi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ankle Joint ◽  
Rat Model ◽  
Platelet Rich Plasma ◽  
Control Group ◽  
Interleukin 17 ◽  
Tnf Α ◽  
Group 2 ◽  
The Right ◽  
And Oxidative Stress

Until now, there is no treatment that cause complete cure of the chronic inflammatory and degenerative disease, osteoarthritis (OA). Moreover, the underlying mechanisms of OA development and progress are not fully elucidated, and the present pharmacological treatment alternatives are restricted and associated with adverse side effects. Thus, the present study was conducted to evaluate the role of platelet-rich plasma (PRP) in the remedy of OA in the rat model in terms of inflammation, ankle histopathological alterations, and oxidative stress. OA was induced in male Wistar rats by injection of MIA (2 mg)/50 µL isotonic saline in the right ankle joint for two successive days in each rat. After the 2nd MIA injection, the osteoarthritic rats were allocated into two groups such as the MIA group (group 2) and MIA + PRP group (group 3). The MIA + PRP group was treated with PRP (50 µL) by injection into the ankle joint of the right hind limb of each rat at days 14, 21, and 28 after the 2nd injection of MIA. The same equivalent volume of saline, as a substitute of PRP, was injected into the ankle joint of each rat of the normal control group (group 1) and MIA group (group 2) at the same tested periods. Swelling of joint, bodyweight, total leucocytes count (TLC), and morphological as well as histological changes of ankle joints were evaluated. Serum lipid peroxides (LPO), glutathione (GSH), and glutathione S-transferase (GST) levels were examined as biomarkers of oxidative stress. Serum tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and interleukin-4 (IL-4) were investigated by ELISA as biomarkers of inflammation. In addition, magnetic resonance imaging (MRI) was carried out to investigate the soft tissues in joints. The obtained results revealed that PRP reduced LPO and increased GSH and GST levels in osteoarthritic rats. Also, PRP significantly diminished serum TNF-α and IL-17 levels, while it increased IL-4 serum levels in rats with MIA-induced OA. Morphological observations, histological analysis, and MRI revealed a gradual diminishing in joint inflammation and destruction of cartilage in PRP-injected osteoarthritic rats. Based on these results, it can be suggested that PRP has antiarthritic potential in MIA-induced OA, which may be mediated via suppression of inflammation and oxidative stress.

Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model

Chemotherapy ◽  
2018 ◽  
Vol 63 (1) ◽  
pp. 39-45
Author(s):  
Bulent Cetin ◽  
Guldal Esendagli Yılmaz ◽  
Berkan Armagan ◽  
Baris Afsar ◽  
Umut Demirci ◽  
...  
Keyword(s):  
Kupffer Cells ◽  
Rat Model ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Control Group ◽  
Albino Rats ◽  
Tissue Samples ◽  
Experimental Rat Model ◽  
Group 3 ◽  
Group 2

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

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 Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6603
Author(s):  
Maryam Baeeri ◽  
Tina Didari ◽  
Madiha Khalid ◽  
Solmaz Mohammadi-Nejad ◽  
Seyed Mojtaba Daghighi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Tissue Injury ◽  
High Mobility ◽  
Male Rats ◽  
Control Group ◽  
Molecular Evidence ◽  
Death Domain ◽  
Tissue Samples ◽  
Tnf Α

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.

scholarly journals Silymarin mitigates diclofenac-induced liver toxicity through inhibition of inflammation and oxidative stress in male rats

2019 ◽  
Vol 8 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Pantea Ramezannezhad ◽  
Ali Nouri ◽  
Esfandiar Heidarian
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Total Bilirubin ◽  
Liver Toxicity ◽  
Treated Group ◽  
Male Rats ◽  
Control Group ◽  
Tnf Α ◽  
Ameliorative Effect ◽  
And Oxidative Stress

Introduction: Diclofenac (DIC) is one of the compounds derived from acetic acid which isknown for its anti-inflammatory and analgesic attributes. Silymarin is a flavonoid compoundwhich is derivate from Silybum marianum seeds. This research was done to assess the protectiverole of silymarin against liver toxicity induced by DIC in male rats.Methods: Randomly, 40 male Wistar rats were assigned into five groups as follows: Group 1:control group, Group 2: DIC-only treated (50 mg/kg, i.p), Group 3: silymarin-only treated (200mg/kg, p.o); Groups 4 and 5: DIC (50 mg/kg, i.p) plus silymarin (100 mg/kg and 200 mg/kg, p.o,respectively) treated. Various biochemical, molecular, and histological parameters were evaluatedin serum and tissue.Results: In the DIC-only treated group, the levels of liver glutathione peroxidase (GPx), superoxidedismutase (SOD), intracellular glutathione (GSH) and catalase (CAT) significantly diminished andthe levels of total bilirubin, alkaline phosphatase (ALP), nitrite, alanine aminotransferase (ALT),malondialdehyde (MDA), serum tumor necrosis factor-α (TNF-α), aspartate aminotransferase(AST), and TNF-α gene expression were remarkably elevated relative to control animals. In otherhands, treatment with silymarin caused a noticeable elevation in GPx, SOD, GSH, CAT and aremarkable reduction in levels of total bilirubin, ALP, nitrite content, ALT, MDA, serum TNF-α,AST and TNF-α gene expression relative to DIC-only treated group. Histopathological injurieswere also improved by silymarin administration.Conclusion: The results confirm that silymarin has an ameliorative effect on liver toxicity inducedby DIC and oxidative stress in male rats.

Swimming Impacts on Pancreatic Inflammatory Cytokines, miR-146a and NF-кB Expression Levels in Type-2 Diabetic Rats

2020 ◽  
Vol 16 (8) ◽  
pp. 889-894 ◽  
Author(s):  
Mohammad Reza Alipour ◽  
Nasibeh Yousefzade ◽  
Fariba Mirzaei Bavil ◽  
Roya Naderi ◽  
Rafighe Ghiasi
Keyword(s):  
Inflammatory Cytokines ◽  
Diabetic Group ◽  
Male Rats ◽  
Swimming Exercise ◽  
Control Group ◽  
Tissue Samples ◽  
Expression Levels ◽  
Tnf Α ◽  
Type 2 Diabetic

Background: Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and type-2 diabetes Objective: This study aimed to evaluate the effect of swimming exercise on pancreatic expression levels of inflammatory cytokines, miR-146a and NF-кB in type-2 diabetic male rats. Method: Twenty- eight male Wistar rats were divided into four groups: control (Con), exercise, diabetes and diabetic exercise (n = 7). Diabetes induction performed by the combination of high-fat diet (HFD, 4 weeks) and streptozotocin (35 mg/kg. ip). After induction of diabetes, the rats swam in the exercise groups for 12 weeks. Then, blood and tissue samples were collected. Result: Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group. Conclusion: Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group.

Antioxidant and anti-inflammatory properties of alpha lipoic acid protect against valproic acid induced liver injury

2020 ◽  
Author(s):  
Marwa Abdeltawab Mohammed ◽  
Doaa Mostafa Gharib ◽  
Hoda Ramadan Reyad ◽  
Alaa Aboud Mohamed ◽  
Fadwa A Elroby ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Adverse Effects ◽  
Lipoic Acid ◽  
Liver Toxicity ◽  
Male Rats ◽  
Control Group ◽  
Alpha Lipoic Acid ◽  
Group 4 ◽  
Anti Inflammatory ◽  
Group 2

Valproic acid (VPA) is one of the most used anti-epileptic drugs inspite of its many adverse effects as anemia, leucopenia, thrombocytopenia, and liver toxicity. The hepatoprotective effect of alpha-lipoic acid (ALA) was confirmed. Aim of the study: The aim of this study was to detect the protective effect of ALA against the adverse effects of VPA. Materials& Methods: Thirty white albino Wistar male rats were divided into 4 groups. Group (1) was the control group; Group (2) included rats that received ALA (100mg/kg/day) orally for 14 days; Group (3) and Group (4) included rats that received VPA (500 mg/kg/day) for 15 days intraperitoneal, but group 4 rats received ALA (100mg/kg/day) orally for 14 days prior to VPA. Blood samples were collected and livers were excised from rats for colorimetric analysis and rt-PCR. Results: Rats that received VPA showed leucopenia, thrombocytopenia, a significant decrease of SOD, glutathione, Nrf2, and Sirt1, besides a significant increase of MDA and TNF alpha. Prior treatment with ALA prevented all these results. Conclusion: ALA protected against VPA-induced liver damage and hematological disturbance via anti-oxidant and anti-inflammatory properties.

Effect of Chinese Herbal Monomer Hairy Calycosin on Nonalcoholic Fatty Liver Rats and its Mechanism

2019 ◽  
Vol 22 (3) ◽  
pp. 194-200 ◽  
Author(s):  
Xiang Liu ◽  
Zhi-Hong Xie ◽  
Chen-Yuan Liu ◽  
Ying Zhang
Keyword(s):  
Fatty Liver ◽  
Liver Tissue ◽  
Liver Homogenate ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Chinese Herbal ◽  
Tnf Α ◽  
Model Control

Background: Chinese herbal monomer hairy Calycosin is a flavonoid extracted from Radix astragali. Aims and Scope: The aim of the research was to investigate the effect and mechanism of Hairy Calycosin on Non-Alcoholic Fatty Liver Dieases (NAFLD) in rats. Materials and Methods: 60 rats were randomly divided into 6 groups, then NAFLD rat models were prepared and treated with different doses of Hairy Calycosin (0.5, 1.0, 2.0 mg/kg) or Kathyle relatively. Results: Both 1.0 mg/kg and 2.0 mg/kg Hairy Calycosin treatment could significantly increase the serum Superoxide Dismutase (SOD) content of the model rats and reduce the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Free Fatty Acid (FFA), IL-6, tumor necrosis factor-alpha (TNF-α) and liver homogenate malondialdehyde (MDA), while 2.0 mg/kg Hairy Calycosin can down-regulate liver tissue cytochrome p450 2E1 (CYP2E1). In the electron microscope, compared with the model control group, the mitochondrial swelling in the hepatocytes of Hairy Calycosin (1.0, 2.0 mg/kg) treatment group was significantly reduced, the ridge on the inner membrane of mitochondria increased, and the lipid droplets became much smaller. Conclusion: Hairy Calycosin can effectively control the lipid peroxidation in liver tissues of rats with NAFLD, and reduce the levels of serum TNF-α, IL-6, MDA and FFA, effectively improve the steatosis and inflammation of liver tissue, and down-regulate the expression of CYP2E1, inhibit apoptosis of hepatocytes.

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