Bone marrow and adipose mesenchymal stem cells attenuate cardiac fibrosis induced by methotrexate in rats

Fikry, Ebtehal Mohammad; Hassan, Wedad A.; Gad, Amany M.

doi:10.1002/jbt.21970

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…Mediators of Inflammation [59]. The MTX-induced increase of caspase 3 has been reported in multiorgan toxicity [4,25,53,60,61]. Our results showed a significant increase in caspase 3 expression in response to MTX treatment.…”

supporting

confidence: 64%

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Al‐Taher

Morsy

Rifaai

et al. 2020

Mediators of Inflammation

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Methotrexate (MTX) is a commonly used chemotherapeutic agent. Oxidative stress and inflammation have been proved in the development of MTX toxicity. Paeonol is a natural phenolic compound with various pharmacological activities including antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of paeonol against MTX-induced cardiac toxicity in rats and to evaluate the various mechanisms that underlie this effect. Paeonol (100 mg/kg) was administered orally for 10 days. MTX cardiac toxicity was induced at the end of the fifth day of the experiment, with or without paeonol pretreatment. MTX-induced cardiac damage is evidenced by a distortion in the normal cardiac histological structure, with significant oxidative and nitrosative stress shown as a significant increase in NADPH oxidase-2, malondialdehyde, and nitric oxide levels along with a decrease in reduced glutathione concentration and superoxide dismutase activity compared to the control group. MTX-induced inflammatory effects are evidenced by the increased cardiac toll-like receptor 4 (TLR4) mRNA expression and protein level as well as increased cardiac tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6 levels along with increased nuclear factor- (NF-) κB/p65 immunostaining. MTX increased apoptosis as shown by the upregulation of cardiac caspase 3 immunostaining. Paeonol was able to correct the oxidative and nitrosative stress as well as the inflammatory and apoptotic parameters and restore the normal histological structure compared to MTX alone. In conclusion, paeonol has a protective effect against MTX-induced cardiac toxicity through inhibiting oxidative and nitrosative stress and suppressing the TLR4/NF-κB/TNF-α/IL-6 inflammatory pathway, as well as causing an associated reduction in the proapoptotic marker, caspase 3.

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supporting

confidence: 64%

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Al‐Taher

Morsy

Rifaai

et al. 2020

Mediators of Inflammation

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“…Methotrexate has a broad spectrum of side effects, including hematological, gastrointestinal, hepatic and renal toxicities as well as lung fibrosis and cardiac damage . Various preclinical studies investigated regenerative effects of MSCs on methotrexate‐induced cardiac and pulmonary fibrosis, kidney and liver injury and have shown beneficial effects regarding organ regeneration and parenchymal functions . However, as most animal work has been done with allogeneic MSCs, further studies are required to investigate if the observed benefits can also be reproduced with pre‐exposed autologous stem cells.…”

Section: Effects Of Chemotherapeutic Anti‐cancer Agents On Mscsmentioning

confidence: 99%

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Rühle

Huber

Saffrich

et al. 2018

Intl Journal of Cancer

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Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.

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“…This evidenced that coagulation and inflammation here were dual systems playing pivotal roles in host defense against MTX-induced lung injury. The elevation of inflammatory mediators in this study might be due to the increase in the stimulation of Toll-like receptor 2 on resident macrophages by MTX which in turn enhanced the emission of proinflammatory cytokines [9,23]. Thus, it was considered that increased inflammation can intensify coagulation that, in turn, boosted inflammation [24,25].…”

Section: Discussionmentioning

confidence: 74%

“…Bone marrow mesenchymal stem cells (MSCs) arise as an attractive alternative to classic pharmacological treatments. In addition to their ability for differentiation and proliferation, MSCs showed potential anti-inflammatory effects [8,9]. Although several studies evaluated the role of MSCs in MTX-induced lung injury models [10,11], no studies scoped on the modulatory effects of MSCs on coagulation as a risk of thrombosis in such models.…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Mesenchymal Stem Cells Regulate Coagulation and Inflammation Together in Methotrexate Induced Lung Injury Rat Model

El-Shinnawy

Abd-Elhalem

Rashed

2019

Braz. arch. biol. technol.

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Clinical research has shed the light on the relation between coagulation and inflammation. Coagulation cascade is activated in lung injury resulting in thrombotic and fibrotic lesions. Such a cascade is initiated by inflammation, then the two systems intense each other. New therapies that modulate coagulation and inflammation will be more successful than therapies targeting only one of them. Mesenchymal stem cells showed anti-inflammatory functions in animal models. The role of mesenchymal stem cells in methotrexate induced lung injury model was evaluated, but no studies scoped on the role of stem cells in coagulation associated with inflammation in such models. This study focuses on the therapeutic role of mesenchymal stem cells against the development of clotting in methotrexate induced lung injury rat model. Results showed that mesenchymal stem cells treatment for 4 weeks caused a decrease in lung activated coagulation factors; protease activated receptor-1, fibrinogen, plasminogen activator inhibitor-1 and platelet count with a decrease in inflammatory factors; tumor necrosis factor-α, interferon-γ, interleukin-8, monocyte chemoattractant protein-1 and total leukocyte count. Thus, mesenchymal stem cells have anti-inflammatory potency against clotting risk in methotrexate induced lung injury model. This opens the outlook for stem cells as a new therapy that moderates coagulation associated with inflammation. HIGHLIGHTS • Stem cells suppress lung coagulation and inflammation. Haggag , N.Z.; et al.

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Bone marrow and adipose mesenchymal stem cells attenuate cardiac fibrosis induced by methotrexate in rats

Cited by 8 publications

References 41 publications

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-κB Inflammatory Pathway

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Bone Marrow Mesenchymal Stem Cells Regulate Coagulation and Inflammation Together in Methotrexate Induced Lung Injury Rat Model

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