The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers—The role of gallic acid

Saygın, Mustafa; Öztürk, Önder; Özmen, Özlem; İlhan, İlter; Gonca, Taner; Gümral, Nurhan; Orhan, Hikmet; Aslankoç, Rahime

doi:10.1016/j.biopha.2016.10.077

Cited by 13 publications

(5 citation statements)

References 33 publications

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“…Recent studies have reported the anti‐biofilm activity of a methanolic extract of pomegranate against bacterial and fungal pathogens (Bakkiyaraj et al, ). Gallic acid has well‐documented anticancer (Singh et al, ), antiinflammatory (Saygin et al, ) and antibacterial effects (Lu et al, ), but antifungal activity has not so far been reported. In the present work, we describe the antifungal activity of GA against C. albicans in vitro and its effects on ergosterol biosynthesis in Trichophyton rubrum membrane.…”

Section: Introductionmentioning

confidence: 99%

Antifungal Activity of Gallic Acid In Vitro and In Vivo

Dawuti³

et al. 2017

Phytotherapy Research

146

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Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Antifungal Activity of Gallic Acid In Vitro and In Vivo

Dawuti³

et al. 2017

Phytotherapy Research

146

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“…Lung damage may result from drug-induced pulmonary toxicity or autoimmune-mediated inflammation 12 . The therapeutic use of MTX is limited by its toxicity 21 which leads to alteration of the dosage regimen, or complete drug withdrawal 12 .…”

Section: Discussionmentioning

confidence: 99%

“…The third group represented the MTX group in which animals were treated with a single i.p. injection of MTX at a dose of 20 mg/kg according to Saygin et al 21 followed by an oral administration of saline for 7 consecutive days. The fourth group was the MTX + PSO group in which animals were treated with a single i.p.…”

Section: Methodsmentioning

confidence: 99%

The potential role of pumpkin seeds oil on methotrexate-induced lung toxicity

Abosrea

Ezz

Mahmoud

et al. 2023

Sci Rep

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Many chemotherapeutic drugs cause adverse pulmonary reactions leading to severe pulmonary disease. Though methotrexate (MTX) is used for the treatment of cancer and other diseases, it is highly toxic with multiple adverse effects including pulmonary toxicity. Essential oils represent an open frontier for pharmaceutical sciences due to their wide range of pharmacological properties. Pumpkin seeds oil (PSO) was used to investigate its ability to alleviate methotrexate-induced lung toxicity in rats. Lung tissue from MTX-treated group revealed a decrease in malondialdehyde, glutathione, and nitric oxide accompanied by a marked inhibition in cholinesterase activity, and enhanced catalase activity, tumor necrosis factor-α, interleukin-6 and vascular endothelial growth factor levels. Analysis of PSO revealed that the oil was rich in hexadecanoic acid, decane methyl esters, squalene, polydecane, docosane, and other derivatives. Administration of PSO ameliorated the oxidant/antioxidant and proinflammatory changes induced by MTX in the lung tissue. Histological examinations confirmed the potency of PSO in reducing the histopathological alterations induced by MTX. Immunohistochemical analysis showed decreased nuclear factor-kappa B and caspase 3 expression after PSO. The present data indicated the protective efficiency of PSO against MTX-induced lung injury by decreasing oxidative damage, inflammation and apoptosis and could thus be recommended as an adjuvant therapy.

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“…GA is a wellknown natural antioxidant of a plant origin as green tea, grapes, and apples. Several literatures reported the wide range of biological activities exerted by GA in different experimental models such as its anti-inflammatory, antioxidant and antiapoptotic effects 22,23 . The effect of GA against CYP-induced lung toxicity has never been explored before, thus our study aimed to investigate the potential protective effect of GA. From the results, GA mitigated cell death and nuclear condensation induced by CYP in WI-38 cells and improved cell morphology due to its anti-inflammatory and antioxidant properties, thus attenuating the oxidative damage as reported by the study of Nikbakht et al who showed that GA protects lungs against bleomycin-induced lung fibrosis 24 .…”

Section: Discussionmentioning

confidence: 99%

Gallic Acid Protects Lung Cells Against Cyclophosphamide-induced Toxicity via Regulating RAGE/NF-κB/autophagy Signaling

El-Emam

2020

Journal of Advanced Pharmacy Research

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Objectives: This study aimed to investigate the protective effect of gallic acid (GA) against cyclophosphamide (CYP)induced lung toxicity with exploring the mechanism of CYP cytotoxicity using normal human lung cells, WI-38 cell line. Methods: WI-38 cells have been categorized into three groups; first group was considered as control, untreated, cells; CYP-group, cells were treated with IC50 concentration of CYP for 24 h; GA+CYP group, cells were pretreated with a selected dose of GA for 24 h then followed by CYP for additional 24 h. After incubation times, cells were collected to evaluate cell viability by trypan blue assay, cell morphology and nuclear condensation by DAPI stain and apoptosis was assessed by AO/EB staining. Lipid peroxidation and total antioxidant capacity were determined in cell lysate biochemically. ELISA technique was applied to determine inflammatory markers (TNF-α and IL-1β), total caspase-3 and LC3-B. RAGE, NF-κB, and Beclin-1 mRNA-expressions were estimated by qRT-PCR. Results: WI-38 cells treated with CYP showed increased cell death by both necrosis and apoptosis with elevated caspase-3 level. Additionally, RAGE expression was up regulated accompanied with activated inflammatory cascade and autophagy. While, GA pretreatment suppressed oxidative stress, inflammatory and autophagy signaling induced by CYP. Conclusion: GA is considered as a promising natural therapeutic option that can halt oxidative damage and RAGE expression activation induced by CYP in lung cells thus preventing lung injury.

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The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers—The role of gallic acid

Cited by 13 publications

References 33 publications

Antifungal Activity of Gallic Acid In Vitro and In Vivo

Antifungal Activity of Gallic Acid In Vitro and In Vivo

The potential role of pumpkin seeds oil on methotrexate-induced lung toxicity

Gallic Acid Protects Lung Cells Against Cyclophosphamide-induced Toxicity via Regulating RAGE/NF-κB/autophagy Signaling

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