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

Taşkın, Banu; Erdoğan, Mehmet; Yiğittürk, Gürkan; Günenç, Damla; Erbaş, Oytun

doi:10.1155/2017/7942531

Cited by 11 publications

(9 citation statements)

References 22 publications

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“…These doses are necessary for rats to account for their faster drug metabolism, which can easily exceed that of a human by a multiple of ≥10. The MTX dose that we choose for our study can be seen from some previous studies [ 13 – 24 ].…”

Section: Methodsmentioning

confidence: 99%

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

Taşkın

Erdoğan

Yiğittürk

et al. 2021

Gastroenterology Research and Practice

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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.

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Section: Methodsmentioning

confidence: 99%

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

Taşkın

Erdoğan

Yiğittürk

et al. 2021

Gastroenterology Research and Practice

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“…In our investigation, we used the published data (5,6) for the anatomical peculiarities and topography of the studied organs in the rabbit for better orientation. This study is a continuation of the previous study for the rabbit glands (6) and deepens the knowledge for these glands, because it is focused on the macrometric parameters.…”

Section: Discussionmentioning

confidence: 99%

“…Methotrexate is typically well tolerated by patients and still the first choice as the cost effective and well-experienced treatment option (5). It has many application fields as a therapeutic agent at low doses in autoimmune diseases and at high doses in many malignancies.…”

Section: Introductionmentioning

confidence: 99%

The role of resveratrol in hepatotoxicity caused by methotrexate

Özgöçmen

Yeşilot

2021

Veterinary Journal of Mehmet Akif Ersoy University

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Methotrexate is an immunosuppressive and antineoplastic drug that may induce hepatotoxicity. Resveratrol is a compound that has a protective effect thanks to its antioxidant role. In present study was aimed to investigate posibble protective effects of resveratrol in methotrexate induced hepatotoxicity. Eighteen Wistar Albino rats were equally divided into three groups: Control, Methotrexate, Methotrexate + Resveratrol. After a single dose of methotrexate (15 mg/kg, i.p.), resveratrol (10 mg/kg, orally) was applied for 7 days. Fallowing 7 days, rats were sacrificed. Histopathological (H-E staining), immunohistochemical (Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa) and biochemical (Total Oxidant Status, Total antioxidants Status and Oxidative Stress Index) analyses were assayed in liver tissue samples. Additionally, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin activities were assayed in serum samples for biochemical analyses. Normal liver tissues were observed in control groups. Histopatholocigal changes, high staining of Tumor Necrosis Factor Alpha, inducible Nitric Oxide Synthases, Nuclear Factor Kappa, increasing levels of tissue Total Oxidant Status, Oxidative Stress Index and decreasing levels of tissue Total antioxidants Status were observed in methotrexate groups. Moreover, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase and Total Biluribin levels increased in methotrexate groups too (p<0.05). However, these findings were lower in the Methotrexate + Resveratrol groups (p<0.05). In this study were observed that oxidant levels could increase after methotrexate applied in the liver, whereas resveratrol alleviated effects of hepatotoxicity by histopathological, immunohistochemical and biochemical analyses.

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“…Apoptosis is one of the important causes of liver cell damage, and it is known that endotoxin is the second blow to CLI and induces chronic liver disease progression via gut-liver axis [ 36 , 37 ] and directly damage liver cells and induce hepatocyte apoptosis [ 38 , 39 ]. Preclinical evidence showed that LA reduced liver injury and decreased oxidative stress response, excessive inflammatory response, and fibrotic progression via downregulating endotoxin levels [ 40 , 41 ]. Therefore, LA was used as positive control in the present study.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). Materials and methods. A network pharmacology combining experimental validation was used to investigate potential mechanisms of QDD against CLI. We firstly screened the bioactive compounds with pharmacology analysis platform of the Chinese medicine system (TCMSP) and gathered the targets of QDD and CLI. Then, we constructed a compound-target network and a protein-protein interaction (PPI) network and enriched core targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. At last, we used a CLI rat model to confirm the effect and mechanism of QDD against CLI. Enzyme-linked immunosorbent assay (ELISA), western blot (WB), and real-time quantitative polymerase chain reaction (RT-qPCR) were used. Results. 48 bioactive compounds of QDD passed the virtual screening criteria, and 53 overlapping targets were identified as core targets of QDD against CLI. A compound-CLI related target network containing 94 nodes and 263 edges was constructed. KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxia-inducible factor (HIF)-1 signaling pathway. Three PPI clusters were identified and enriched in hepatitis B and tumor necrosis factor (TNF) signaling pathway, apoptosis and hepatitis B pathway, and peroxisome pathway, respectively. Animal experiment indicated that QDD decreased serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), and IL-17 and increased prothrombin time activity (PTA) level. WB and RT-qPCR analyses indicated that, compared with the model group, the expression of cysteinyl aspartate specific proteinase-9 (caspase-9) protein, caspase-3 protein, B-cell lymphoma-2 associated X protein (Bax) mRNA, and cytochrome c (Cyt c) mRNA was inhibited and the expression of B-cell lymphoma-2 (Bcl-2) mRNA was enhanced in the QDD group. Conclusions. QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. This study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically.

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

Cited by 11 publications

References 22 publications

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

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

The role of resveratrol in hepatotoxicity caused by methotrexate

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

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