Methotrexate reduces keratinocyte proliferation, migration and induces apoptosis in HaCaT keratinocytes in vitro and reduces wound closure in Skh1 mice in vivo

Medellín-Luna, Mitzzy Fátima; Castañeda-Delgado, Julio Enrique; Fernández-Ruiz, Julio César; Ochoa-Gonzalez, Fatima; Troncoso-Vázquez, Lorena; García-Cruz, Salvador; Zapata-Zúñiga, Martín; Serrano, Carmen; Portales-Pérez, Diana Patricia; Enciso-Moreno, José Antonio; Cervantes-Villagrana, Alberto R.

doi:10.1016/j.jtv.2020.10.004

Cited by 6 publications

(3 citation statements)

References 17 publications

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“…However, it is also used in low doses to effectively treat inflammatory diseases such as rheumatoid arthritis and Crohn’s disease ( 62 , 63 ). The methotrexate doses in animal experiments ranges from 2mg/kg to 200mg/kg ( 64 , 65 ). For the dose in our experiments, due to lack of hamster pharmacokinetics we used the mice pharmacokinetics by Lobo ED’s lab ( 66 ), and to avoid methotrexate-induced toxicity ( 67 ) to consider a lower test dose of 2mg/kg/day for short-term treatment.…”

Section: Methodsmentioning

confidence: 99%

Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model

et al. 2022

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BackgroundDrug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease.MethodsHere, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC50 = 0.4 μM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms.ResultsOur in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals.ConclusionsWe demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.

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Section: Methodsmentioning

confidence: 99%

Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model

et al. 2022

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“…In a hairless mouse model treated with MTX, there was a delayed proliferation phase that markedly affected the wound-healing process. 6 Moreover, mice treated with high-dose or repeated-dose MTX demonstrated scarred skin, reduced collagen production, and disappearance of skin elements, such as sebaceous glands and hair follicles. Although molecular and preclinical evidence supports MTX's role in impaired wound healing, clinical studies suggest that low-dose MTX is safe and does not affect the incidence of postoperative wound complications.…”

Section: Antineoplastic Agentsmentioning

confidence: 99%

Wound-Healing Effects of Common Antineoplastic Agents and Perioperative Considerations for the Orthopaedic Surgeon

Okay,

Connolly,

Gonzalez

et al. 2024

J Am Acad Orthop Surg

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In oncologic patients, optimal postoperative wound healing is crucial for the maintenance of systemic therapies and improved survival. Although several risk factors for postoperative wound complications have been identified, the clinical effect of new antineoplastic agents on wound healing remains uncertain. The available literature on the effect of antineoplastic agents in wound healing is complex to analyze because of other confounding risk factors such as radiation therapy and certain patient-specific variables. Available perioperative drug recommendations are based on database opinion and case reports from adverse event alerts. This review highlights the characteristics of old and new antineoplastic agents commonly used in the treatment of sarcoma, carcinoma, and other cancers and their potential effects on the wound-healing process. It also aims to provide perioperative treatment cessation recommendations to guide orthopaedic surgeons and prevent drug-related wound complications to the fullest extent possible.

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“…Thus, the elicitation of an inflammatory cascade of events is paramount to the body's response to tissue injury. Importantly, immunosuppressive drug regimens used to treat SLE, such as long-term systemic corticosteroids, methotrexate, mycophenolate mofetil, azathioprine, and drugs interfering with the Interleukin-2 mediated immune response (e.g., voclosporin), as well as the presence of SLE per se, counteract and impair the wound healing process [8][9][10][11][12][13]. This potentially complicates the management of burn patients with comorbid SLE and necessitates special consideration on how to approach burn management in this unique population.…”

Section: Introductionmentioning

confidence: 99%

Burn Management in a Patient With Acute Exacerbation of Comorbid Systemic Lupus Erythematosus

Davis¹,

Pang²,

Abidi³

et al. 2023

Cureus

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A 28-year-old female presented to the burn unit with 2% total body surface area second-degree burns to the right flank and right breast after accidentally spilling coffee on herself while hospitalized for an acute exacerbation of systemic lupus erythematosus (SLE) in the form of neuromyelitis optica spectrum disorder. We document her inpatient management, which was challenging because of the contradictory relationship between typical management of SLE exacerbations (i.e., immunosuppressive medication regimens) and the body’s post-burn healing process, which is inherently inflammatory in nature. Even with a high-dose immunosuppressive medication regimen, our patient’s second-degree burns healed with non-operative management without significant adverse events. Adding to a small yet growing body of literature addressing the clinical presentation and management of burn wounds in the setting of an acute SLE exacerbation, our case suggests that clinicians must carefully weigh the risks of surgical intervention with those of non-operative management when approaching burn care during an acute rheumatologic disease flare up.

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Methotrexate reduces keratinocyte proliferation, migration and induces apoptosis in HaCaT keratinocytes in vitro and reduces wound closure in Skh1 mice in vivo

Cited by 6 publications

References 17 publications

Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model

Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model

Wound-Healing Effects of Common Antineoplastic Agents and Perioperative Considerations for the Orthopaedic Surgeon

Burn Management in a Patient With Acute Exacerbation of Comorbid Systemic Lupus Erythematosus

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