Efficacy of 17α-ethynylestradiol-3-sulfate for severe hemorrhage in minipigs in the absence of fluid resuscitation

Miller, M. F.; Keith, James C.; Berman, Jonathan; Grudzinskas, Charles; Hubbard, William J.; Peck, Carl C.; Scott, Charles; Chaudry, Irshad H.

doi:10.1097/ta.0000000000000237

Cited by 21 publications

(59 citation statements)

References 27 publications

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“…21,26,27 Furthermore, sulfated ethinyl estrogens are highly soluble in the water, which is essential for effective drug distribution in tissues. 17,27,31 The rationale of DAI recovery by EE-3-SO 4 , however, is still not clear. We presume that EE-3-SO 4 alleviates traumatic axonal injury via increasing glucose uptake to stabilize ion channels.…”

Section: Discussionmentioning

confidence: 99%

“…42 EE-3-SO 4 can increase the cerebral circulation via its vasodilatory effects. 17,31,38 Neutralizing free radicals in the damaged area using antioxidants during the early stage of injury can result in significant reduction of inflammation, edema, and axonal breakdown. 51 Estrogens have strong antiinflammatory and antioxidant effects.…”

Section: Discussionmentioning

confidence: 99%

“…EE-3-SO 4 treatment in the absence of fluid resuscitation significantly increased survival of minipigs and rats that underwent severe hemorrhage (60% blood loss). 17,31 These data led us to adopt EE-3-SO 4 as the drug of choice for TBI treatment studies, made more relevant by a dearth of effective pharmaceuticals available to treat TBI. 6 Rather than EE-3-SO 4 having a lower rate of degradation or excretion, it is possible that it can be "recycled."…”

Section: Treatment Of Traumatic Brain Injury With 17α-ethinylestradiomentioning

confidence: 99%

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Treatment of traumatic brain injury with 17α-ethinylestradiol-3-sulfate in a rat model

Kim¹,

Yu²,

Cam-Etoz

et al. 2017

Journal of Neurosurgery

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OBJECTIVE17α-ethynylestradiol-3-sulfate (EE-3-SO4) is a highly water-soluble synthetic estrogen that has an extended half-life (∼ 10 hours) over that of naturally occurring estrogen (∼ 10 minutes). In this study, EE-3-SO4 was evaluated in a lateral fluid percussion–induced traumatic brain injury (TBI) model in rats.METHODSA total of 9 groups of Sprague-Dawley rats underwent craniectomy. Twenty-four hours later, lateral fluid percussion was applied to 6 groups of animals to induce TBI; the remaining 3 groups served as sham control groups. EE-3-SO4 (1 mg/kg body weight in 0.4 ml/kg body weight) or saline (vehicle control) was injected intravenously 1 hour after TBI; saline was injected in all sham animals. One day after EE-3-SO4/saline injection, intracranial pressure (ICP), cerebral perfusion pressure (CPP), and partial brain oxygen pressure (PbtO2) were measured in Groups 1–3 (2 TBI groups and 1 sham group), and brain edema, diffusion axonal injury, and cerebral glycolysis were assessed in Groups 4–6 using MRI T2 mapping, diffusion tensor imaging (DTI), and FDG-PET imaging, respectively. Four days after dosing, the open-field anxiety of animals was assessed in Groups 7–9 by measuring the duration that each animal spent in the center area of an open chamber during 4 minutes of monitoring.RESULTSEE-3-SO4 significantly lowered ICP while raising CPP and PbtO2, compared with vehicle treatment in TBI-induced animals (p < 0.05). The mean size of cerebral edema of TBI animals treated with EE-3-SO4 was 25 ± 3 mm3 (mean ± SE), which was significantly smaller than that of vehicle-treated animals (67 ± 6 mm3, p < 0.001). Also, EE-3-SO4 treatment significantly increased the fractional anisotropy of the white matter in the ipsilateral side (p = 0.003) and cerebral glycolysis (p = 0.014). The mean duration that EE-3-SO4-treated animals spent in the center area was 12 ± 2 seconds, which was significantly longer than that of vehicle-treated animals (4 ± 1 seconds; p = 0.008) but not different from that of sham animals (11 ± 3 seconds; p > 0.05).CONCLUSIONSThese data support the clinical use of EE-3-SO4 for early TBI treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Treatment Of Traumatic Brain Injury With 17α-ethinylestradiomentioning

confidence: 99%

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Treatment of traumatic brain injury with 17α-ethinylestradiol-3-sulfate in a rat model

Kim¹,

Yu²,

Cam-Etoz

et al. 2017

Journal of Neurosurgery

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“…The estrogen used here was 17β-estradiol, the most potent form of estrogen in females and has been widely employed in other researches [15]. The dose of 1 mg/kg BW of 17β-estradiol was chosen based on previous studies of estrogen in vivo, which was found to be optimal in producing salutary effects such as organ protection and maintenance of hemodynamics following adverse circulatory conditions [24,25].…”

Section: Treatment: 17β-estradiolmentioning

confidence: 99%

Estrogen Maintains Skeletal Muscle in Septic Rats Associated with Altering Hypothalamic Inflammation and Neuropeptides

Zhao

Shi

et al. 2017

Horm Metab Res

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Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17β-estradiol (1 mg/kg) or saline. Twenty-four hours later, all animals were killed and their hypothalamus and skeletal muscles were harvested for analysis. Muscle wasting markers, hypothalamic neuropeptides, and hypothalamic inflammatory markers were measured. As a result, lipopolysaccharide administration caused a significant increase in muscle wasting, hypothalamic inflammation, and anorexigenic neuropeptides (POMC and CART) gene expression, and a significant decrease in orexigenic neuropeptides (AgRP and NPY) gene expression. Administration of estrogen signifcantl attenuated lipopolysaccharide-induced muscle wasting (body weight and extensor digitorum longus loss [52 and 62 %], tyrosine and 3-methylhistidine release [17 and 22 %], muscle ring fnger 1 [MuRF-1; 65 %], and muscle atrophy F-box [MAFbx] gene expression), hypothalamic inflammation (Tumor necrosis factor-α and interlukin-1β [69 and 70%]) as well as alteration of POMC, CART and AgRP (61, 37, and 1008 %) expression.In conclusion, estrogen could alleviate sepsis-induced muscle wasting and it was associated with reducing hypothalamic inflammation and alteration of hypothalamic neuropeptides.

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“…Trauma-hemorrhagic shock is known to be followed by many life-threatening sequelae [1], [2]. Trauma-hemorrhagic shock induces the overproduction of proinflammatory mediators, which plays an important role in the process of organ injury [3]–[5].…”

Section: Introductionmentioning

confidence: 99%

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

et al. 2014

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Neutrophil activation is associated with the development of organ injury after trauma–hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma–hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma–hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma–hemorrhagic shock-induced organ injury in rats.

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Efficacy of 17α-ethynylestradiol-3-sulfate for severe hemorrhage in minipigs in the absence of fluid resuscitation

Cited by 21 publications

References 27 publications

Treatment of traumatic brain injury with 17α-ethinylestradiol-3-sulfate in a rat model

Treatment of traumatic brain injury with 17α-ethinylestradiol-3-sulfate in a rat model

Estrogen Maintains Skeletal Muscle in Septic Rats Associated with Altering Hypothalamic Inflammation and Neuropeptides

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

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