Allylpyrocatechol attenuates methotrexate-induced hepatotoxicity in a collagen-induced model of arthritis

De, Soumita; Kundu, Sunanda; Chatterjee, Uttara; Chattopadhyay, Subrata; Chatterjee, Mitali

doi:10.1080/10715762.2018.1466391

Cited by 17 publications

(5 citation statements)

References 45 publications

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“…According to previous studies, MTX increases IL-6, TNF-α, and IL-1β levels. 39,47,60,61 Also, the inflammatory markers significantly reduced in the FA +MTX groups in the current study. These findings are in line with previous studies, indicating the FA potential to thwart the CCl 4 -induced release of inflammatory factors.…”

Section: Dovepresssupporting

confidence: 53%

<p>Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity</p>

Roghani¹,

Kalantari‬²,

Khodayar³

et al. 2020

DDDT

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Introduction: In multiple studies, involvement of oxidative stress in the pathogenesis of methotrexate (MTX)-mediated liver damage has been confirmed. Use of many drugs has been examined experimentally in order to prevent or diminish oxidative stress. However, no study has yet examined the effects of ferulic acid (FA) on MTX-induced liver damage. This study aimed at evaluating the effects of FA on protection against liver damage induced by MTX in mice. Materials and Methods: In this the mice were divided into five groups in a random manner: I) control; II) MTX (20 mg/kg); III and IV) FA (50 and 100 mg/kg) + MTX; and V) FA (100 mg/kg), and we measured serum factors, oxidative stress and inflammatory factors. Results: In the MTX group, accumulation of inflammatory cells, accumulation of red blood cell (RBC), and nuclear pyknosis (NP) were detected in the liver. In line with the histological data, the levels of nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α increased (TNF-α), whereas the reduced glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) content reduced in the MTX group. However, FA ameliorated these hazardous effects in the antioxidant and anti-inflammatory systems in MTX-treated groups. Conclusion: Based on our findings, oxidative stress impairment and MTX-induced liver damage were ameliorated following FA pretreatment at both histological and biochemical levels. Therefore, FA can be effectively used in abrogation of MTX-induced toxicity.

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Section: Dovepresssupporting

confidence: 53%

<p>Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity</p>

Roghani¹,

Kalantari‬²,

Khodayar³

et al. 2020

DDDT

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“…These results are consistent with a previous study showing that systemic exposure and mean residence time of methotrexate were increased by oral administration of glycyrrhizin and methotrexate (14). However, in that report, the dosage was 5 mg/kg methotrexate, and the route of administration was oral, assuming a low dose of methotrexate (5-25 mg/week) as in clinical use for rheumatoid arthritis (15,16). High-dose methotrexate was 8-12 g/m 2 (17)(18)(19)(20); in other words, the dose of methotrexate was 100-300 mg/kg per week in patients with osteosarcoma and 30-100 mg/kg per week in patients with lymphoma and leukemia.…”

Section: Figure 3 Plasma Concentration-time Profiles Of Alanine Aminotransferase (Alt) In Rats After Intravenous Administration Of Mtx Atsupporting

confidence: 91%

Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity

Abe

Higurashi

Takahashi

et al. 2021

In Vivo

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Background/Aim: High-dose methotrexate is a therapy for acute leukemia, malignant lymphoma, and osteosarcoma. Glycyrrhizin has been used to treat hepatic dysfunction caused by high-dose methotrexate. However, few studies have investigated the interaction between glycyrrhizin and high-dose methotrexate. Materials and Methods: Male Wistar rats were treated with high-dose methotrexate (500 or 1,000 mg/kg) alone, or with co-administration of 100 mg/kg glycyrrhizin. Plasma concentrations of methotrexate, alanine aminotransferase, aspartate aminotransferase, and total bilirubin were measured. Results: At both methotrexate doses, the blood concentration of methotrexate was significantly increased and total clearance was significantly reduced using co-administration of glycyrrhizin compared with methotrexate alone, which led to increased levels of hepatic enzymes. These results suggest that glycyrrhizin significantly increases the plasma level and delays the clearance of methotrexate, resulting in hepatic toxicity. Conclusion: The concomitant use of methotrexate and glycyrrhizin should be considered with caution.Methotrexate is an antifolate drug that inhibits DNA synthesis and repair, and cellular replication (1, 2). High-dose methotrexate, defined as 500 mg/m 2 or higher administered intravenously, is used for a variety of cancer types, such as acute lymphoblastic leukemia, lymphoma, and osteosarcoma (3). However, high-dose methotrexate can cause a variety of toxic side-effects, including kidney injury, myelosuppression, mucositis, neurotoxicity and hepatotoxicity, which cause significant morbidity and delay treatment, leading to inferior anticancer outcomes (4). To prevent and mitigate toxicities, the serum concentrations of methotrexate and creatinine, and urine output are monitored, and supportive care is given, including intravenous hydration, urinary alkalinization, and rescue with leucovorin administration (5, 6). Recently, therapeutic drug monitoring has been implemented to reduce the side-effects of high-dose methotrexate by screening and managing its pharmacokinetics.Hepatic toxicity has a high incidence during high-dose methotrexate treatment, causing elevation in the levels of hepatic transaminases such as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (7-9). To treat hepatic toxicity, an increased dose of leucovorin, along with glycyrrhizin, is often administered. Glycyrrhizin has antiinflammatory and anti-allergy effects (10) and is widely used in the treatment of liver diseases to improve liver function, as well as in the treatment of other conditions, such as pruritus and urticaria (11,12).However, few studies have investigated the interaction between glycyrrhizin and methotrexate. It is important to elucidate drug interactions that may influence the efficacy and safety of high-dose methotrexate therapy. In particular, we considered the need for a basic study to reflect the clinical use of high-dose methotrexate therapy. Therefore, we evaluated the pharmacokinetic interactions ...

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“…As a result we found that PCr extract has an anti-inflammatory activity and that MTX-induced caspase-3 and TNF-alpha increase could be prevented by treatment. One of the liver fibrosis parameters is the amount of tissue collagen present (36). It has already been proven by various researchers that MTX tends to increase the level of tissue collagen (37).…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Petroselinum crispum (Parsley) Extract Against Methotrexate-Induced Hepatotoxicity

Ertaş¹,

Turan²,

Özbeyli³

et al. 2021

ejb

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Objective: By inhibiting the synthesis of thymidine and purine, and thereby DNA synthesis, Methotrexate (MTX), suppresses the proliferation of cancer cells. It is thought that the side-effect mechanism is related to oxidant molecules derived from MTX metabolism. In this study, we examined whether the Petroselinum crispum extracts (PCr; parsley) of which the antioxidant properties have been previously shown, was protective against MTX induced liver damage.Materials and Methods: Sprague Dawley rats (female/male; 200-250 g) were used. MTX was injected intraperitoneally and PCr extract was given orally. A single dose of 20mg/kg MTX was administered to the groups that were to experience hepatotoxicity. Then, a physiological saline (MTX group) or PCr (2 g/kg, MTX + PCr group) treatment was applied for 5 days. The same treatments were applied to the other groups (control group, PCr group) for 5 days after a single dose saline injection. At the end of the study, the biochemical parameters were examined in the blood and liver tissues taken from animals sacrificed by decapitation.Results: MTX caused a significant increase in malondialdehyde and collagen levels and myeloperoxidase and caspase-3 activities, while glutathione levels were found to have decreased. PCr treatment showed protective efficacy by preventing these increases. Conclusion:It appears that the administration of PCr to MTX treated rats prevented the accumulation of lipid peroxides, inflamatory reactions and depletion of antioxidant glutathione, and thus protected liver tissues against oxidative stress.

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Allylpyrocatechol attenuates methotrexate-induced hepatotoxicity in a collagen-induced model of arthritis

Cited by 17 publications

References 45 publications

<p>Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity</p>

<p>Alleviation of Liver Dysfunction, Oxidative Stress and Inflammation Underlies the Protective Effect of Ferulic Acid in Methotrexate-Induced Hepatotoxicity</p>

Concomitant Use of High-dose Methotrexate and Glycyrrhizin Affects Pharmacokinetics of Methotrexate, Resulting in Hepatic Toxicity

Protective Effects of Petroselinum crispum (Parsley) Extract Against Methotrexate-Induced Hepatotoxicity

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