l-arginine alleviates doxorubicin-induced endothelium-dependent dysfunction by promoting nitric oxide generation and inhibiting apoptosis

Li, Xunan; Gu, Jun; Zhang, Yunlong; Feng, Shuidong; Huang, Xin; Liu, Yang; Yang, Xiaolei

doi:10.1016/j.tox.2019.05.016

Cited by 19 publications

(17 citation statements)

References 26 publications

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“…The negative impact of Dox on endothelial cell function has been previously reported in cultured cells and ranges from induction of apoptosis via elevation in ROS (15) to decreased barrier function (33). In addition, several reports have shown the negative impact of Dox on vascular function in rodent models (11,16) or in the development of large vessel defects in subjects undergoing anticancer therapy (9,24). Fewer reports exist that have investigated the impact on the human microcirculation (27), none of which directly assessed MV function in the coronary circulation.…”

Section: Discussionmentioning

confidence: 93%

Detrimental effects of chemotherapy on human coronary microvascular function

Hader

Zinkevich

Toro

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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Chemotherapy (CT) is a necessary treatment to prevent the growth and survival of cancer cells. However, CT has a well-established adverse impact on the cardiovascular (CV) system, even years after cessation of treatment. The effects of CT drugs on tumor vasculature have been the focus of much research, but little evidence exists showing the effects on the host microcirculation. Microvascular (MV) dysfunction is an early indicator of numerous CV disease phenotypes, including heart failure. The goal of this study was to evaluate the direct effect of doxorubicin (Dox) on human coronary MV function. To study the effect of CT on the cardiac MV function, flow-mediated dilation (FMD), pharmacologically-induced endothelial dependent dilation to acetylcholine (ACh), and smooth muscle-dependent dilation to papaverine were investigated. Vessels were freshly isolated from atrial appendages of adult patients undergoing cardiopulmonary bypass surgery or from cardiac tissue of pediatric patients, collected at the time of surgery to repair congenital heart defects. Isolated vessels were incubated in endothelial culture medium containing vehicle or Dox (100 nm, 15–20 h) and used to measure dilator function by video microscopy. Ex vivo treatment of adult human coronary microvessels with Dox significantly impaired flow-mediated dilation (FMD). Conversely, in pediatric coronary microvessels, Dox-induced impairment of FMD was significantly reduced in comparison with adult subjects. In both adult and pediatric coronary microvessels, ACh-induced constriction was reversed into dilation in the presence of Dox. Smooth muscle-dependent dilation remained unchanged in all groups tested. In vessels from adult subjects, acute treatment with Dox in clinically relevant doses caused significant impairment of coronary arteriolar function, whereas vessels from pediatric subjects showed only marginal impairment to the same stressor. This interesting finding might explain the delayed onset of future adverse CV events in children compared with adults after anthracycline therapy. NEW & NOTEWORTHY We have characterized, for the first time, human microvascular responses to acute ex vivo exposure to doxorubicin in coronary vessels from patients without cancer. Our data show an augmented impairment of endothelial function in vessels from adult subjects compared with pediatric samples.

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Section: Discussionmentioning

confidence: 93%

Detrimental effects of chemotherapy on human coronary microvascular function

Hader

Zinkevich

Toro

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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“…Arginine is a non-essential amino acid and has been reported to inhibit active oxidative stress, acute inflammatory response, and hence alleviate cell injury. Arginine also promotes the production of NO (nitric oxides) to rescue vascular damage [36][37][38]. Regulation of arginine metabolism is reported to be neuroprotective by administration of melatonin after MCAO [39].…”

Section: Discussionmentioning

confidence: 99%

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

et al. 2020

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Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.

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“…Nutraceuticals supplement: three supplement combinations [231][232][233][234][235][236][237][238][239][240] are necessary to ameliorate the biological processes of endothelial dysfunction (e.g., l-citrulline [241][242][243], l-arginine [244,245]), oxidative stress and inflammation [246]; publications on this topic are extensive and therefore it is not discussed here.…”

Section: Preventionmentioning

confidence: 99%

“…Both oral l-citrulline and/or l-arginine supplementation increases nitric oxide bioavailability levels in plasma and tissue [241][242][243][244][245]308]. L-arginine restores doxorubicin-induced vascular dysfunction in cancer treatments by attenuating vascular nitric oxide release and apoptosis [231]. Emerging evidence suggests that increasing nitric oxide bioavailability or endothelial nitric oxide synthase activity activates telomerase and delays endothelial cell senescence [309].…”

Section: Preventionmentioning

confidence: 99%

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

Phua

2021

Medicines

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Background: The etiology of benign prostatic hyperplasia and prostate cancer are unknown, with ageing being the greatness risk factor. Methods: This new perspective evaluates the available interdisciplinary evidence regarding prostate ageing in terms of the cell biology of regulation and homeostasis, which could explain the timeline of evolutionary cancer biology as degenerative, inflammatory and neoplasm progressions in these multifactorial and heterogeneous prostatic diseases. Results: This prostate ageing degeneration hypothesis encompasses the testosterone-vascular-inflamm-ageing triad, along with the cell biology regulation of amyloidosis and autophagy within an evolutionary tumorigenesis microenvironment. Conclusions: An understanding of these biological processes of prostate ageing can provide potential strategies for early prevention and could contribute to maintaining quality of life for the ageing individual along with substantial medical cost savings.

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l-arginine alleviates doxorubicin-induced endothelium-dependent dysfunction by promoting nitric oxide generation and inhibiting apoptosis

Cited by 19 publications

References 26 publications

Detrimental effects of chemotherapy on human coronary microvascular function

Detrimental effects of chemotherapy on human coronary microvascular function

Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

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