Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress

Kalemci, Serdar; Topal, Yaşar; Celi̇k, Serkan; Yılmaz, Nigar; Beydilli, Halil; Koşar, Mehmet İlkay; Dirican, Nigar; Altuntaş, İrfan

doi:10.3892/etm.2015.2542

Cited by 15 publications

(18 citation statements)

References 26 publications

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“…These results indicated that silibinin suppressed airway inflammation caused by SiONPs exposure. These effects caused by silibinin treatment were supported by previous studies [33,34], wherein silibinin alleviated inflammatory response in radiation-or methotrexate-induced pulmonary injury via suppression of cytokine production.…”

Section: Discussionsupporting

confidence: 72%

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

Lim

Shin

Seo

et al. 2020

Cells

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Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

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Section: Discussionsupporting

confidence: 72%

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

Lim

Shin

Seo

et al. 2020

Cells

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“…Methotrexate (MTX) is an antineoplastic drug that may be related to folic acid metabolism (Kalemci et al, ). MTX, which is an antagonist of folic acid, is used as an antimetabolite in cancer chemotherapy, leukemia, mammary gland tumors, osteosarcoma, psoriasis, and autoimmune disorders, inhibiting the synthesis of RNA, thymidylate, proteins, and especially DNA (Ali, Rashid, Nafees, Hasan, & Sultana, ; Gautam et al, ; Kalemci et al, ). MTX causes toxic effects in various organs such as kidneys, livers, and bone marrows (Ulusoy, Öztürk, & Sönmez, ) but the precise mechanism in kidney toxicity by MTX remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

et al. 2017

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Silymarin (SLY) and naringin (NRG) are natural flavonoids that have been reported to have many benefits and medicinal properties. The present study was designed to investigate the protective effect of SLY and NRG against methotrexate (MTX)‐induced nephrotoxicity in experimental animals. Rats were subjected to oral pretreatment of SLY (25 and 50 mg/kg body weight (b.w.)/day) and NRG (50 and 100 mg/kg b.w./day) for 7 days against renal toxicity induced by single intraperitoneal administration of MTX (20 mg/kg b.w.). MTX resulted in an increase in serum toxicity markers, lipid peroxidation, and reduction in activities of antioxidant enzymes. Additionally, MTX provoked inflammatory responses by increasing the levels of TNF‐α, IL‐1β, IL‐6, NF‐κB, and activation of COX‐2 and iNOS. Furthermore, MTX administration caused apoptosis and autophagy by increasing activity of Caspase‐3 and light chain 3B level. Conversely, SLY and NRG therapy significantly decreased these values in rats. This study demonstrated that SLY and NRG protect against MTX‐induced nephrotoxicity. Practical applications Chemotherapeutic drugs have been used for cancer treatment for many years. However, in the treatment process, they may damage organs such as liver and kidney, prolong the treatment process and negatively affects patient welfare. This study revealed that silymarin and naringin exhibited potent anti‐inflammatory, antiapoptotic, and antiautophagic effect in renal injury caused by methotrexate, a chemotherapeutic drug. Therefore, treatment silymarin and naringin can be used for the beneficial effect against methotrexate‐induced kidney damage in cancer chemotherapy.

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“…The increased rate of inflammatory cell infiltration in pulmonary tissue may be due to mitogen-activated protein kinase (MAPK) and Akt pathways. 24 Quercetin, an antioxidant flavonoid widely distributed in plants, green leafy vegetables and fruits has shown beneficial effects in various diseases. The dissemination of quercetin and its metabolites in rats are well distributed in tissues whereby highest concentration noted in lungs and lowest in brain and spleen.…”

mentioning

confidence: 99%

Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study

David¹,

Satyanarayana²,

Parasuraman³

et al. 2016

IJPER

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Objective: To study the effect of quercetin on methotrexate induced toxicity and to observe the histopathological changes. Materials and Methods: Thirty male rats were divided into 5 different groups with each group consisting of six rats. The Group I was a control and they were treated with 10 ml/kg of carboxymethyl cellulose. The Group II, III, IV and V animals were treated with methotrexate 0.125 mg/kg; methotrexate 0.25 mg/kg; methotrexate (0.125 mg/kg) + quercetin (500 mg/kg); and methotrexate (0.25 mg/kg) + quercetin (500 mg/kg), respectively. All drugs were administered orally through oral gavage once daily for 14 days. At the end of the study, blood samples were collected from all the animals in each group. The animals were then sacrificed and organs were collected for histopathological analysis. Results: Methotrexate 0.125 and 0.25 mg/kg significantly increased the levels of liver enzymes such as AST, ALT, ALP and total protein and renal markers such as urea and creatinine. The animals treated with quercetin along with methotrexate showed significant improvement on methotrexate induced liver and renal toxicities. Methotrexate significantly reduced the levels of haemoglobin and blood sugar and which was partially reversed by quercetin. The notable histopathological changes in lungs, liver and kidneys were observed with methotrexate treated animals and this was protected by quercetin. Conclusion: Methotrexate produced significant pathological changes at 0.250 mg/kg and possible ameliorative effect of quercetin observed in lung, liver and kidney. Quercetin 500 mg/kg significantly inhibited the methotrexate induced toxicity in liver and kidneys.

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Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress

Cited by 15 publications

References 26 publications

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties

Ameliorative Effect of Quercetin on Methotrexate Induced Toxicity in Sprague-Dawley Rats: A Histopathological Study

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