Dasatinib prevent hepatic fibrosis induced by carbon tetrachloride (CCl<sub>4</sub>) via anti-inflammatory and antioxidant mechanism

Mohammadalipour, Adel; Karimi, Jamshid; Khodadadi, Iraj; Solgi, Ghasem; Hashemnia, Mohammad; Sheikh, Nasrin; Bahabadi, Majid

doi:10.1080/08923973.2016.1263860

Cited by 26 publications

(15 citation statements)

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“…Their dose and duration of treatment were based on the previous studies and according to the histopathologic finding and serum enzymes changes. Therefore, the treatment period was conducted from the 4th to 12th week of fibrosis …”

Section: Methodsmentioning

confidence: 99%

“…Fixed tissues were stained with hematoxylin‐eosin, Masson's trichrome and periodic acid–Schiff (PAS) . For immunohistochemistry, after preparation of the slides, they were incubated with a primary monoclonal α‐SMA antibody as it was explained in previous publication .…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the inhibition of some RTKs pathway components such as VEGFR and PDGFR, and nRTKs such as c‐Abl, and c‐Src, along with rho‐kinase, led to the development of different treatments …”

Section: Introductionmentioning

confidence: 99%

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Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Mohammadalipour

Hashemnia

Goudarzi

et al. 2019

Clin Exp Pharma Physio

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It has been shown that both nilotinib as a tyrosine kinase inhibitor, and atorvastatin as a rho‐kinase inhibitor, have antifibrotic effects. Therefore, considering the relationship between these two pathways, this study aimed to investigate the effects of their co‐treatment against hepatic stellate cells (HSCs) activation and liver fibrosis. For this purpose, the activation of HSCs coincided with these therapies. Also, liver fibrosis by carbon tetrachloride (CCl4) was induced in male Wistar rats and treated simultaneously with these compounds. The expression of alpha‐smooth muscle actin (α‐SMA), connective tissue growth factor (CTGF), Ras homolog gene family, and member A (RhoA)/Rho‐associated protein kinase (ROCK) in HSCs were measured. The expression of transforming growth factor beta‐1 (TGF‐β1), its receptor (TβRII), CTGF, and platelets derived growth factor (PDGF), in the livers, were also investigated, all by real‐time PCR and western blot analysis. Also, histopathologic and immunohistochemical evaluations were performed to evaluate changes in liver fibrosis during treatment. The results indicated the down‐regulation of RhoA/ROCK, CTGF, and α‐SMA, and inhibition of the HSCs activation toward myofibroblasts. The results also showed that the combined use of atorvastatin and nilotinib has significantly higher inhibitory effects. The antifibrotic effects of atorvastatin and nilotinib co‐administration were also observed by histopathologic and immunohistochemical observations, and inhibiting the expression of TGF‐β1, TβRII, CTGF, and PDGF. Taken together, this study revealed that co‐administration of nilotinib–atorvastatin has novel antifibrotic effects, by inhibiting RhoA/ROCK, and CTGF pathway. Therefore, the importance of the common pathway of RhoA/ROCK and CTGF, in reducing fibrosis may almost be concluded.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Mohammadalipour

Hashemnia

Goudarzi

et al. 2019

Clin Exp Pharma Physio

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“…Targeting senescent cells with senolytic drugs might slow down or prevent fibrosis processes in different tissues and organs [16,[25][26][27]. Currently, quercetin (Q) and dasatinib (D), administered alone or in combination (D+Q), are the most studied senolytic drugs [28].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, quercetin (Q) and dasatinib (D), administered alone or in combination (D+Q), are the most studied senolytic drugs [28]. Different authors have reported anti-fibrotic effects of these drugs in tissues such as kidney, lung, and liver [25][26][27]. Quercetin is a flavonoid with antioxidant, anti-inflammatory, immunoprotective, and even anticarcinogenic effects [29].…”

Section: Introductionmentioning

confidence: 99%

Dasatinib Plus Quercetin on Uterine Age-Related Dysfunction and Fibrosis in Mice

Cavalcante

Saccon

Nunes

et al. 2019

Preprint

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23Female reproductive function is negatively impacted by age. Animal and human studies show 24 that fibrosis of the uterus contributes to gestational outcomes. Collagen deposition in the 25 myometrial and endometrial layers is the main change related to uterine aging. Senolytic 26 therapies are a potential option for reducing diseases and health complications related to aging. 27 We investigated effects of aging and the senolytic drug combination of dasatinib plus quercetin 28 (D+Q) on uterine fibrosis. A total of 40 mice, 20 young females (03-months) and 20 old females 29 (18-months), were analyzed. Young (Y) and old (O) animals were divided into groups of 10 30 mice, with one treatment (T) group (YT and OT) and another control (C) group (YC and OC).31Comparative analysis of Pi3k/Akt1/mTor and p53 gene expression among the 4 groups was 32 performed to test effects of age and treatment on collagen deposition in uterine tissue. Uterine 33 levels of microRNAs (miR34a, miR34b, miR34c, miR146a, miR449a, miR21a, miR126a, and 34 miR181b) were evaluated. Aging promoted downregulation of genes of the Pi3k/Akt1/mTor 35 signaling pathway (p=0.005, p=0.031, and p=0.028, respectively) as well as a reduction in 36 expression of miR34c (p=0.029), miR126a (p=0.009), and miR181b (p=0.007). D+Q treatment 37 increased p53 gene expression (p=0.041) and decreased levels of miR34a (p=0.016). Our results 38 demonstrate a role for the Pi3k/Akt1/mTor signaling pathway in uterine aging and suggest for the 39 first time a possible anti-fibrotic effect in the uterus of D+Q senolytic therapy.40 Introduction 43 The reproductive profile of women has been changing over the last few decades. Older 44 maternal age by the first gestation and an increased number of pregnancies after 40 years of age 45 are phenomena observed worldwide, impacting directly on gestational results [1]. Studies in 46 humans and animals suggest a strong relationship between pregnancy loss and maternal age [2, 47 3]. In addition to advanced age, other gynecological conditions are related to fertility, such as 48 polycystic ovary syndrome, leiomyomas, and endometriosis [4]. It is known that ovarian 49 dysfunction is the major factor responsible for these poor reproductive outcomes, but other 50 reproductive organs are involved in this complex process [2]. 51 An increase in uterine volume with aging is common in some species of rodents, mostly 52 due to endometrial cystic hyperplasia, as opposed to what occurs in menopausal women, in 53 whom uterine atrophy is usually evident [3, 5]. The most obvious histological change in the aged 54 uterus is the collagen deposition (fibrosis) in the muscle layers and stroma [3]. Mechanisms 55 involved in this uterine fibrosis remain unclear [6]. Collagen deposition in tissues occurs as a 56 result of chronic inflammatory processes involving several pathways: inflammatory interleukins, 57 growth factors, caspases, oxidative stress products, and accumulation of senescent cells [6]. 58 These chronic inflammatory pathways are also involve...

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Oxidative Medicine and Novel Pharmacological Treatment Approaches in Liver Disease

Tripathi,

Singh,

Mourya

et al. 2023

Adaptation Under Stressful Environments Through Biological Adjustments and Interventions

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Dasatinib prevent hepatic fibrosis induced by carbon tetrachloride (CCl₄) via anti-inflammatory and antioxidant mechanism

Abstract: Our findings indicate that Dasatinib can be cautiously an anti-fibrotic, anti-inflammatory and anti-oxidative agent in clinical setting.

Cited by 26 publications

References 41 publications

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Dasatinib Plus Quercetin on Uterine Age-Related Dysfunction and Fibrosis in Mice

Oxidative Medicine and Novel Pharmacological Treatment Approaches in Liver Disease

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Dasatinib prevent hepatic fibrosis induced by carbon tetrachloride (CCl4) via anti-inflammatory and antioxidant mechanism

Abstract: Our findings indicate that Dasatinib can be cautiously an anti-fibrotic, anti-inflammatory and anti-oxidative agent in clinical setting.

Cited by 26 publications

References 41 publications

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Increasing the effectiveness of tyrosine kinase inhibitor (TKI) in combination with a statin in reducing liver fibrosis

Dasatinib Plus Quercetin on Uterine Age-Related Dysfunction and Fibrosis in Mice

Oxidative Medicine and Novel Pharmacological Treatment Approaches in Liver Disease

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Product

Resources

About

Dasatinib prevent hepatic fibrosis induced by carbon tetrachloride (CCl₄) via anti-inflammatory and antioxidant mechanism