Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats

Kalantar, Mojtaba; Kalantari‬, Heibatullah; Goudarzi, Mehdi; Khorsandi, Layasadat; Bakhit, Samira; Kalantar, Hadi

doi:10.1016/j.pharep.2019.04.004

Cited by 48 publications

(28 citation statements)

References 44 publications

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“…Previous study reported that reactive oxygen species can damage the endothelial glycocalyx of the kidneys and lungs and modulate HPA expression of glomerular adriamycin nephropathy [38,39]. Additionally, crocin has been reported to improve methotrexin-induced liver injury by inhibiting oxidative stress in rats [40]. However, further studies are needed to determine whether crocin's protective effect on glycocalyx degradation of LPS-induced ARDS mice and LPS-stimulated HUVECs is also related to oxidative injury.…”

Section: Figmentioning

confidence: 98%

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

Zhang

Zhu

et al. 2020

Inflamm. Res.

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Objective To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). Methods Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocin on HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet-dry ratio and through fluorescein isothiocyanate-albumin assay. Then, protein levels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence. Results This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effects of crocin on LPS-induced ARDS and elaborated their underlying mechanism. Conclusion Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Figmentioning

confidence: 98%

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

Zhang

Zhu

et al. 2020

Inflamm. Res.

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“…Previous studies have confirmed the major involvement of NO in the pathogenesis of MTX toxicity. 46,47 The high NO content reacts with superoxide anions producing versatile oxidant peroxynitrite and activating nuclear factor kappa B (NF-κB). 47 In our study, MDA level and NO content significantly decreased following FA pretreatment.…”

Section: Dovepressmentioning

confidence: 99%

<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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“…Morphology was assessed by two independent pathologists under a light microscope (Olympus BX63; Olympus Corporation). The degree of liver injury was scored according to Kalantar et al (16). Indices including inflammatory cell infiltration, RBC congestion, and nuclear pyknosis were examined.…”

Section: Animalsmentioning

confidence: 99%

Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats

et al. 2019

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Non-alcoholic fatty liver disease (NAFLd) is characterized by hepatic steatosis, insulin resistance and inflammation; however, the exact pathogenesis of NAFLD is not fully understood. Green tea polyphenols (GTP) exhibit beneficial effects against metabolic syndrome. However, the effect of GTP on NAFLD remains largely unknown. The aim of the present study was to investigate the effects of GTP on NAFLD in high-fat diet (HFD)-induced rats. The NAFLD rat model was induced with a HFD for 8 weeks. A total of 30 adult male Sprague Dawley rats were randomly divided into three groups: i) Normal control group; ii) HFD group; and iii) HFD with GTP group. Hematoxylin and eosin and Oil Red O analyses were performed. The levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) and inflammatory cytokines in the serum, as well as oxidative stress markers and hepatic lipids in the liver were measured. In addition, parameters associated with glucose metabolism were also assessed. Western blotting and RT-qPCR were used to determine the expression levels of 5' adenosine monophosphate-activated protein kinase (AMPK). HFD-induced rats exhibited features associated with NAFLD. GTP intervention significantly reduced serum ALT and AST levels. Fasting serum glucose, insulin resistance and hepatic lipid levels were all decreased in the GTP-treated rats. GTP also significantly decreased the levels of TNF-α, IL-6 and malondialdehyde. In contrast, superoxide dismutase levels were increased in the liver. Furthermore, GTP also significantly increased phosphorylation of AMPK and attenuated histopathological changes indicative of injury in liver tissue. GTP has a protective effect on HFD-induced hepatic steatosis, insulin resistance and inflammation, and the underlying mechanism may involve the AMPK pathway.

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Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats

Cited by 48 publications

References 44 publications

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways

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

Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats

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