Role of rivaroxaban in sunitinib-induced renal injuries via inhibition of oxidative stress-induced apoptosis and inflammation through the tissue nacrosis factor-α induced nuclear factor-κappa B signaling pathway in rats

Al-Harbi, Naif O.; Imam, Faisal; Al-Harbi, M. M.; Khan, Mohammad Rashid; Qamar, Wajhul; Afzal, Muhammad; Algahtani, Mohammad; Alobaid, Saad; Alfardan, Ali S.; Alshammari, Abdulrahman; Albekairi, Thamer H.; Alharbi, Khalid Saad

doi:10.1007/s11239-020-02123-6

Cited by 15 publications

(12 citation statements)

References 42 publications

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“…Many researchers have confirmed the potential anti-inflammatory role of RVX. The previous studies of Jhaveri et al (2011), Basile et al, 2012and his colleagues in 2012, Ma et al, 2018and his coworkers in 2017, and Al-Harbi et al (2020 were in line with the above-discussed literature that RVX has anti-inflammatory effects. Also, RVX dampened the inflammatory response in the ischemic brain (Dittmeier et al, 2016).…”

Section: Discussionsupporting

confidence: 76%

“…It has a similar efficacy to the standard therapy and is associated with a significantly reduced risk of bleeding (Robertson and Kesteven., 2014). RVX has antioxidant (Al-Harbi et al, 2020) and anti-inflammatory (Jhaveri et al, 2011) effects. RVX could protect the experimental animals from inflammation by blocking factor Xa, which is considered as an accelerator for the generation of the proinflammatory mediators (Jhaveri et al, 2011;Al-Harbi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…RVX has antioxidant (Al-Harbi et al, 2020) and anti-inflammatory (Jhaveri et al, 2011) effects. RVX could protect the experimental animals from inflammation by blocking factor Xa, which is considered as an accelerator for the generation of the proinflammatory mediators (Jhaveri et al, 2011;Al-Harbi et al, 2020). Also, Dittmeier and his coworkers (2016) found that the pretreatment with RVX attenuates stroke severity in rats by a dual antithrombotic and anti-inflammatory mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

et al. 2021

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Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks—the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor‐kappa B (NF‐κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kβ, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p-value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kβ signaling pathway.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

et al. 2021

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“…Lung tissue sample was homogenized with lysis buffer having protease enzyme inhibitor cocktail for extraction of protein and bicinchoninic acid protein assay method was used for the quantitative analysis of protein sample for running western blot analysis as described previously ( Lowry et al, 1951 , Barakat et al, 2001 , Al-Harbi et al, 2020 ). Concisely, 25–50 µg samples from each group were loaded in the well of 10% SDS-polyacrylamide gel electrophoresis (PAGE) and separated by electrophoresis followed by transfer of blot from the gel to PVDF/nitrocellulose membrane (Bio-Rad, USA) by electrophoresis.…”

Section: Biochemical Analysismentioning

confidence: 99%

Protective effect of Apremilast against LPS-induced acute lung injury via modulation of oxidative stress and inflammation

Al-Harbi

Imam

Al-Harbi

et al. 2022

Saudi Journal of Biological Sciences

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“…Information on the effect of sunitinib on kidney tissue damage is very limited. According to Al‐Harbi et al., [23] sunitinib caused damage to the renal tissue at a dose of 50 mg/kg in rats, while in another study, [24] when sunitinib was administered at a dose of 100 mg/kg, it reduced NF‐κB and TNF‐α mRNA levels. Korashy et al [24] .…”

Section: Discussionmentioning

confidence: 96%

The Effects of Sunitinib in Healthy and Cisplatin‐Induced Rats

Demirtaş

Gürbüzel

Akbas

et al. 2023

Chemistry & Biodiversity

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Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups – (1) control group (C) administered interperitoneally with a single dose 0.9 % saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1β and TGF‐β3 expression levels when administered alone; it increased ALT, AST, and IL‐38 levels. When sunitinib was given to the cisplatin‐induced rats, it was observed that the increase in ALT, AST, and IL‐38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.

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Role of rivaroxaban in sunitinib-induced renal injuries via inhibition of oxidative stress-induced apoptosis and inflammation through the tissue nacrosis factor-α induced nuclear factor-κappa B signaling pathway in rats

Cited by 15 publications

References 42 publications

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

Protective effect of Apremilast against LPS-induced acute lung injury via modulation of oxidative stress and inflammation

The Effects of Sunitinib in Healthy and Cisplatin‐Induced Rats

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