Angiotensin II type 1 receptor blockade attenuates gefitinib-induced cardiac hypertrophy via adjusting angiotensin II-mediated oxidative stress and JNK/P38 MAPK pathway in a rat model

Alanazi, Wael A.; Alhamami, Hussain N.; Alharbi, Metab; Alhazzani, Khalid; Alanazi, Abdulrahman; Alsanea, Sary; Ali, Nemat; Alasmari, Abdullah F.; Alanazi, Ahmed Z.; Alotaibi, Moureq R.; Alswayyed, Mohammed

doi:10.1016/j.jsps.2022.06.020

Cited by 7 publications

(9 citation statements)

References 49 publications

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“…In addition to the antioxidant effects of losartan in aortic tissues, it also normalized GSH, SOD and LPO levels in the renal and cardiac tissues, leading to the prevention of the systemic oxidative stress induced by tivozanib. In subjects treated with VEGFR-TKIs such as sorafenib and gefitinib, research revealed that these drugs increased free radical production and oxidative damage, which contribute to causing kidney and heart diseases [ 40 , 41 , 42 ]. Our recent study demonstrated that AngII type1 receptor blockade attenuated oxidative stress and AngII/AT1R/MAPK signaling pathway in gefitinib-induced cardiac hypertrophy [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…In subjects treated with VEGFR-TKIs such as sorafenib and gefitinib, research revealed that these drugs increased free radical production and oxidative damage, which contribute to causing kidney and heart diseases [ 40 , 41 , 42 ]. Our recent study demonstrated that AngII type1 receptor blockade attenuated oxidative stress and AngII/AT1R/MAPK signaling pathway in gefitinib-induced cardiac hypertrophy [ 42 ]. Based on the current finding, the signaling pathways involved in tivozanib-induced nephrotoxicity and cardiotoxicity need further investigations to be clarified.…”

Section: Discussionmentioning

confidence: 99%

“…β-actin monoclonal antibody (ABclonal Technology, Woburn, MA, USA) was used as a housekeeping protein. All the primary antibodies were used in a dilution of 1:1000 [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

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Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model

Alanazi

El-Nagar

et al. 2023

Pharmaceuticals

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Tivozanib is a triple vascular endothelial growth factor receptor inhibitor, recently approved for the treatment of refractory advanced renal cell carcinoma. Clinical studies showed that around 46% of patients who received tivozanib suffer from hypertension in all grades. Thus, the present study was conducted to identify the role of angiotensin-II (AngII) in the mechanism underlying tivozanib-induced vascular toxicity and hypertension. C57BL/6 male mice received tivozanib (1 mg/kg) with or without losartan (10 or 30 mg/kg) for 3 weeks. Blood pressure was recorded every 3 days, and proteinuria was measured every week. On day 21, all mice were euthanized, and samples were harvested for further analysis. Tivozanib elevated blood pressure until systolic blood pressure reached 163 ± 6.6 mmHg on day 21 of treatment with low urination and high proteinuria. AngII and its receptors, endothelin-1, and oxidative stress markers were significantly increased. While nitric oxide (NO) levels were reduced in plasma and aortic tissues. AngII type 1 receptor blockade by losartan prevented these consequences caused by tivozanib and kept blood pressure within normal range. The results showed that AngII and ET-1 might be potential targets in the clinical studies and management of hypertension induced by tivozanib.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model

Alanazi

El-Nagar

et al. 2023

Pharmaceuticals

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“…The last group was received VAL for a week and then received GEF and VAL for three weeks. The dose of VAL and GEF were chosen based on previous research papers ( Alhazzani et al, 2021 , Alanazi et al, 2022 ). All animals were weighed daily for calculation of medication doses and weight gain percentage in all groups.…”

Section: Methodsmentioning

confidence: 99%

Valsartan prevents gefitinib-induced lung inflammation, oxidative stress, and alteration of plasma metabolites in rats

Alanazi

Alhamami

Alshamrani

et al. 2023

Saudi Journal of Biological Sciences

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“…Production of ROS stimulates the phosphorylation of p38 and the mitogen-activated protein kinase (MAPK) signaling pathway, leading to myocardial hypertrophy. 12 Additionally, AT-R1 downregulation can decrease many pathological pathways, including Ang-II/ AT-R1 signaling pathways, and control Ang-II-induced cardiac hypertrophy. 13,14 In recent years, more and more studies have indicated that photo-nutrients are new therapy choices to treat cardiac-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Ellagic acid protects against angiotensin II‐induced hypertrophic responses through ROS‐mediated MAPK pathway in H9c2 cells

Lee,

Jou,

Chou

et al. 2024

Environmental Toxicology

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The early myocardial response of hypertension is an elevation of angiotensin‐II (Ang‐II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT‐R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti‐inflammatory and anti‐oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang‐II‐induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang‐II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang‐II‐increased cell surface area and pro‐hypertrophic gene expression in H9c2. EA reduced Ang‐II‐caused AT‐R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang‐II‐enhanced p38 and extracellular‐signal‐regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang‐II stimulation also reversed NF‐κB activity and iNOS expression. This study shows that EA protects against Ang‐II‐induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species‐mediated mitogen‐activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang‐II‐induced myocardial hypertrophy.

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Angiotensin II type 1 receptor blockade attenuates gefitinib-induced cardiac hypertrophy via adjusting angiotensin II-mediated oxidative stress and JNK/P38 MAPK pathway in a rat model

Cited by 7 publications

References 49 publications

Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model

Mechanism Underlying Triple VEGFR Inhibitor Tivozanib-Induced Hypertension in Mice Model

Valsartan prevents gefitinib-induced lung inflammation, oxidative stress, and alteration of plasma metabolites in rats

Ellagic acid protects against angiotensin II‐induced hypertrophic responses through ROS‐mediated MAPK pathway in H9c2 cells

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