Tamoxifen protects against acute tumor necrosis factor α-induced cardiac injury via improving mitochondrial functions

Zhao, Yunfeng; Wang, Li Ming; Chaiswing, Luksana; Yen, Hsiu-Chuan; Oberley, Terry D.; Lien, Yu‐Chin; Lin, Shu Mei; Mattson, Mark P.; Clair, Daret St.

doi:10.1016/j.freeradbiomed.2005.11.009

Cited by 21 publications

(18 citation statements)

References 27 publications

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“…Tamoxifen could also act to enhance antioxidant mitochondrial functions in cells to exert its antioxidant effects. Along these lines, tamoxifen has been reported to be a potent inhibitor of the mitochondrial permeability transition in rat liver mitochondria (18,19) and has been shown to improve mitochondrial respiratory function in cells and enhance superoxide scavenging activity of mitochondria (20). Our study provides evidence that tamoxifen can enhance the endogenous antioxidant defense mechanisms in cells in the ischemic cortex, because we observed that tamoxifen markedly increased mitochondrial MnSOD immunoreactivity levels in the ipsilateral cortex penumbra at 24 and 96 h after cerebral ischemia.…”

Section: Discussionsupporting

confidence: 60%

“…Interestingly, a number of studies have suggested that tamoxifen, or its active metabolite 4-OH-tamoxifen, possesses free radical-scavenging and antioxidant activity in vitro and in vivo (15)(16)(17)(18)(19). Tamoxifen has also been shown recently to improve mitochondrial respiratory function and enhance superoxide-scavenging activity of mitochondria in the heart (20). Based on these findings, the present study was designed to examine whether tamoxifen modulates superoxide anion (O 2 Ϫ ) production in the brain after cerebral ischemia in the ovariectomized female rat as a potential mechanism of neuroprotection.…”

Section: Institute Of Molecular Medicine and Genetics School Of Medimentioning

confidence: 99%

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Tamoxifen Neuroprotection in Cerebral Ischemia Involves Attenuation of Kinase Activation and Superoxide Production and Potentiation of Mitochondrial Superoxide Dismutase

et al. 2008

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The purpose of this study was to enhance our understanding of the mechanisms of neuronal death after focal cerebral ischemia and the neuroprotective effects of tamoxifen (TMX). The phosphorylation state of 31 protein kinases/signaling proteins and superoxide anion (O 2 ؊ ) production in the contralateral and ipsilateral cortex was measured after permanent middle cerebral artery occlusion (pMCAO) in ovariectomized rats treated with placebo or TMX. The study revealed that pMCAO modulated the phosphorylation of a number of kinases/proteins in the penumbra at 2 h after pMCAO. Of significant interest, phospho-ERK1/2 (pERK1/2) was elevated significantly after pMCAO. TMX attenuated the elevation of pERK1/2, an effect correlated with reduced infarct size. In situ detection of O 2 ؊ production showed a significant elevation at 1-2 h after pMCAO in the ischemic cortex with enhanced oxidative damage detected at 24 h. ERK activation may be down- . However, estrogen can have undesired stimulatory effects on the breast and uterus, which raises concern for a potential increased risk of developing breast and uterine cancers. These potential limitations have kindled interest in the development and therapeutic use of nonsteroidal selective estrogen receptor modulators. Along these lines, work by our laboratory and others has shown that the selective estrogen receptor modulator tamoxifen can significantly reduce infarct size in both transient and permanent occlusion/reperfusion models of cerebral ischemia (7-10). Kimelberg and colleagues (7) were the first to report a neuroprotective action of tamoxifen after stroke in male animals, an effect later extended to female animals by our laboratory (9). The effect of tamoxifen was shown to be independent of cerebral blood flow changes, indicating a potential direct neuroprotective effect in the brain by tamoxifen. In line with this suggestion is previous work showing that tamoxifen readily crosses the blood-brain barrier and accumulates in the brain (11). Tamoxifen has also been implicated to be neuroprotective in animal models of Parkinson's disease, where it has been shown to protect the striatum against methamphetamine-induced toxicity and prevent striatal dopamine depletion in male and female animals (12-15).The mechanism of how tamoxifen exerts neuroprotection is unclear. Kimelberg and colleagues (7,8) have shown that tamoxifen can inhibit excitatory amino acid release and nitric oxide synthase activity after temporary cerebral ischemia in male rodents, which may be important for its neuroprotective effects. Interestingly, a number of studies have suggested that tamoxifen, or its active metabolite 4-OH-tamoxifen, possesses free radical-scavenging and antioxidant activity in vitro and in vivo (15)(16)(17)(18)(19). Tamoxifen has also been shown recently to improve mitochondrial respiratory function and enhance superoxide-scavenging activity of mitochondria in the heart (20). Based on these findings, the present study was designed to examine whether tamoxifen modulates superoxide anio...

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Section: Discussionsupporting

confidence: 60%

Section: Institute Of Molecular Medicine and Genetics School Of Medimentioning

confidence: 99%

Tamoxifen Neuroprotection in Cerebral Ischemia Involves Attenuation of Kinase Activation and Superoxide Production and Potentiation of Mitochondrial Superoxide Dismutase

et al. 2008

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“…23 El Gebeily et al demonstrated that tamoxifen could possibly reduce cardiac arrhythmia by interfering with the potassium channel current, which also implied the protective potential of tamoxifen. 24 Zhao et al revealed that by improving mitochondrial function in an animal model, tamoxifen protected against cardiac-injuring tumor necrosis factor α, 25 which was a novel potential therapeutic target for atrial fibrosis. 26 In another subcellular study, tamoxifen was found to induce manganese superoxide dismutase, a mitochondrial antioxidant enzyme, which protected mouse cardiomyocytes from adriamycin injury.…”

Section: Resultsmentioning

confidence: 99%

Association of Tamoxifen Use and Reduced Cardiovascular Events Among Asian Females With Breast Cancer

Yang

Huang

et al. 2014

Circ J

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“…Mounting reports demonstrated that ROS played important roles in injury of cardiomyocyte and exerted a significant effect on the development of cardiac hypertrophy [29][30][31][32]. Tsujimoto et al reported that pressure overload induced cardiac hypertrophy accompanied by increased ROS level, while treatment with free radical scavenger significantly attenuated hypertrophic response [33].…”

Section: Discussionmentioning

confidence: 99%

Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways

Liu

Cao

Tang

et al. 2010

The Journal of Nutritional Biochemistry

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Tamoxifen protects against acute tumor necrosis factor α-induced cardiac injury via improving mitochondrial functions

Cited by 21 publications

References 27 publications

Tamoxifen Neuroprotection in Cerebral Ischemia Involves Attenuation of Kinase Activation and Superoxide Production and Potentiation of Mitochondrial Superoxide Dismutase

Tamoxifen Neuroprotection in Cerebral Ischemia Involves Attenuation of Kinase Activation and Superoxide Production and Potentiation of Mitochondrial Superoxide Dismutase

Association of Tamoxifen Use and Reduced Cardiovascular Events Among Asian Females With Breast Cancer

Allicin protects against cardiac hypertrophy and fibrosis via attenuating reactive oxygen species-dependent signaling pathways

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