Resveratrol and FGF1 Synergistically Ameliorates Doxorubicin-Induced Cardiotoxicity via Activation of SIRT1-NRF2 Pathway

Lu, Guangping; Liu, Qingbo; Gao, Ting; Li, Jiahao; Zhang, Jingjing; Chen, Ou; Cao, Cong; Mao, Min; Xiao, Mengjie; Zhang, Xiaohui; Wang, Jie; Guo, Yuanfang; Tang, Yufeng; Gu, Junlian

doi:10.3390/nu14194017

Cited by 19 publications

(10 citation statements)

References 43 publications

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“…In a similar study, it was reported that Paraquat which is known as a pesticide, increases connective tissue growth factor expression and impairs lung fibroblast proliferation and viscoelasticity (Zhang et al, 2014). It has also been reported that Res has a synergistic protective effect against cardiotoxicity and hepatotoxicity in experimental studies (Lu et al, 2022;Xu et al, 2022). Thus, it is seen that the immuno-histochemical results of FGF-1 in lung sections are very similar to the literature.…”

Section: Discussionsupporting

confidence: 77%

Protective effects of resveratrol on permethrin-induced fetotoxicity in rats

YÜKSEL¹,

ASLAN

Tosun

et al. 2023

Anatolian Journal of Botany

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Synthetic pyrethroid insecticides have been widely used for years to be protected from the harmful effects of insects and control disease vectors. In this study, the potential effects of resveratrol, a polyphenolic compound, against the potential toxicity of permethrin, an effective pyrethroid derivative, on the fetus were investigated. In the study, Wistar female rats were divided into four groups Control, Sham, Permethrin, and Permethrin + Resveratrol. The lung, liver, kidney, and small intestine development of fetuses were evaluated histopathologically. Also, Bone Morphogenetic Protein 4 (BMP-4) in bone tissue development and Fibroblast Growth Factor-1 (FGF-1) expressions in the lung were examined immunohistochemically. All structures in the control and sham groups were normal. Permethrin caused epithelial damage, regression in bronchial and primitive alveolar development in the lung; congestion, edema, and sinusoidal dilatation around the central vein in the liver; tubular epithelial degeneration, regression in glomeruli and tubule formation in the kidney; epithelial degeneration and irregularity in the villus structure in the small intestine. Immunohistochemical results indicated that permethrin administration decreased BMP-4 levels in bone tissue and FGF-1 levels in the lung. After resveratrol application was found to greatly alleviate histopathological and immunohistopathological variability in all tissues. Oral consumption of permethrin by pregnant rats caused growth retardation and tissue damage in many different tissues in offspring. Intake of resveratrol during pregnancy showed protective effects against fetotoxicity caused by permethrin.

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Section: Discussionsupporting

confidence: 77%

Protective effects of resveratrol on permethrin-induced fetotoxicity in rats

YÜKSEL¹,

ASLAN

Tosun

et al. 2023

Anatolian Journal of Botany

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“…The speculation for this special phenomenon is that FGF1 promotes the initiation of autophagy leading to a compensatory increase in SQSTM1/p62 ( Geffken et al, 2022 ). Another speculation is that during the action of FGF1, a different pathway is activated, leading to an increase in the expression of SQSTM1/p62 and thus promoting endometrial thickening ( Feng et al, 2017 ; Lu et al, 2022 ). But the details need to be explored in subsequent studies.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 1 ameliorates thin endometrium in rats through activation of the autophagic pathway

Zhu

Yin

et al. 2023

Front. Pharmacol.

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Background: Thin endometrium is a reproductive disorder that affects embryo implantation. There are several therapies available for this disease, however they are not so effective. Fibroblast growth factor 1 (FGF1) is a member of fibroblast growth factor superfamily (FGFs), and it has been demonstrated that FGF1 expression was altered in samples collected from patients with thin endometrium. However, it is unclear if FGF1 could improve thin endometrium. The aim of this study was to investigate whether FGF1 have a therapeutic effect on thin endometrium.Methods: A model of thin endometrium induced by ethanol was constructed to investigate the effect and mechanism of action of FGF1 in thin endometrium. In the characterization experiments, 6–8 weeks female rats (n = 40) were divided into four groups: i) Control group; ii) Sham group; iii) Injured group; (iv) FGF1 therapy group. Endometrial tissues would be removed after three sexuel cycles after molding. Morphology and histology of the endometrium were evaluated by visual and hematoxylin and eosin staining. Masson staining and expression of α-SMA in endometrium showed the degree of endometrial fibrosis. Western blotting (PCNA、vWF and Vim) and immunohistochemistry (CK19 and MUC-1) demonstrated the effect of FGF1 on cell proliferation and angiogenesis. Moreover, immunohistochemistry (ER and PR) was used to explore the function of endometrium. The remaining rats (n = 36) were divided into three groups: i) Injured group; ii) FGF1 therapy group; and iii) 3-methyladenine. Western blotting (p38、p-p38、PI3K 、SQSTM1/p62、beclin-1 and LC3) was used to explore the mechanisms of FGF1.Results: In FGF1 therapy group, the morphology and histology of endometrium improved compared with the model group. Masson staining and the expression level of α-SMA showed that FGF1 could decrease the fibrotic area of endometrium. Besides, changes in ER and PR expression in the endometrium suggested that FGF1 could restore endometrium-related functions. Western blotting and immunohistochemistry revealed that PCNA, vWF, Vim, CK19 and MUC-1 were significantly increased after FGF1 treatment compared with the thin endometrium. In addition, Western blotting showed that p38, p-p38, PI3K, SQSTM1/p62, beclin-1 and LC3 levels were higher in FGF1 group than in the injured group.Conclusion: FGF1 application cured the thin endometrium caused by ethanol through autophagy mechanism.

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“…Toxic chemicals and electrophiles promote the shift toward oxidative stress and trigger rapid translocation of Nrf2 into the nucleus where it binds to antioxidant response elements (AREs) of target genes including NAD(P)H dehydrogenase [quinone] 1 ( Nqo1 ), heme oxygenase 1 ( HMOX1 ) and superoxide dismutase 1, -2 ( SOD1 , -2 ) ( Figure 5 ) [ 55 ]. The targeted upregulation of gene expression of this endogenous antioxidant response results in potent antioxidant and cytoprotective activities to effectively ameliorate DOX-induced oxidative stress, which is similarly used by potent Nrf2 inducers such as resveratrol [ 60 , 61 ], sulforaphane [ 62 , 63 , 64 ] and bardoxolone-methyl [ 65 , 66 ]. Our study is the first to report decreased Keap1 protein expression following acute DOX treatment in human iPSC-CMs, which is consistent with newly synthesized Nrf2 escaping Keap1-dependent ubiquitination and rapid proteasomal degradation ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Carvedilol Phenocopies PGC-1α Overexpression to Alleviate Oxidative Stress, Mitochondrial Dysfunction and Prevent Doxorubicin-Induced Toxicity in Human iPSC-Derived Cardiomyocytes

Uche,

Dai,

Lai

et al. 2023

Antioxidants

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Doxorubicin (DOX), one of the most effective and widely used anticancer drugs, has the major limitation of cancer treatment-related cardiotoxicity (CTRTOX) in the clinic. Reactive oxygen species (ROS) generation and mitochondrial dysfunction are well-known consequences of DOX-induced injury to cardiomyocytes. This study aimed to explore the mitochondrial functional consequences and associated mechanisms of pretreatment with carvedilol, a ß-blocking agent known to exert protection against DOX toxicity. When disease modeling was performed using cultured rat cardiac muscle cells (H9c2 cells) and human iPSC-derived cardiomyocytes (iPSC-CMs), we found that prophylactic carvedilol mitigated not only the DOX-induced suppression of mitochondrial function but that the mitochondrial functional readout of carvedilol-pretreated cells mimicked the readout of cells overexpressing the major regulator of mitochondrial biogenesis, PGC-1α. Carvedilol pretreatment reduces mitochondrial oxidants, decreases cell death in both H9c2 cells and human iPSC-CM and maintains the cellular ‘redox poise’ as determined by sustained expression of the redox sensor Keap1 and prevention of DOX-induced Nrf2 nuclear translocation. These results indicate that, in addition to the already known ROS-scavenging effects, carvedilol has a hitherto unrecognized pro-reducing property against the oxidizing conditions induced by DOX treatment, the sequalae of DOX-induced mitochondrial dysfunction and compromised cell viability. The novel findings of our preclinical studies suggest future trial design of carvedilol prophylaxis, such as prescreening for redox state, might be an alternative strategy for preventing oxidative stress writ large in lieu of the current lack of clinical evidence for ROS-scavenging agents.

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Resveratrol and FGF1 Synergistically Ameliorates Doxorubicin-Induced Cardiotoxicity via Activation of SIRT1-NRF2 Pathway

Cited by 19 publications

References 43 publications

Protective effects of resveratrol on permethrin-induced fetotoxicity in rats

Protective effects of resveratrol on permethrin-induced fetotoxicity in rats

Fibroblast growth factor 1 ameliorates thin endometrium in rats through activation of the autophagic pathway

Carvedilol Phenocopies PGC-1α Overexpression to Alleviate Oxidative Stress, Mitochondrial Dysfunction and Prevent Doxorubicin-Induced Toxicity in Human iPSC-Derived Cardiomyocytes

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