Acetazolamide and CO2

Harris, Alon; Tippke, Susanne; Sievers, C; Picht, Greda; Lieb, Wolfgang; Martin, Bruce

doi:10.1097/00061198-199602000-00007

Cited by 36 publications

(3 citation statements)

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“…Tumor perfusion plays a key role in providing O 2 and substrate for metabolism and eliminating metabolic waste products. Acetazolamide can induce transient vasocontraction during increases in pCO 2 and more sustained vasorelaxation, with some variability between vascular beds, but the mechanisms of action and dependency on pH are disputed [ 33 , 57 , 58 ]. We perform Laser Doppler Flowmetry to evaluate tissue perfusion but observe no convincing influence of acetazolamide on perfusion of the breast cancer tissue or the hind limb (Fig.…”

Section: Resultsmentioning

confidence: 99%

Carbonic anhydrases reduce the acidity of the tumor microenvironment, promote immune infiltration, decelerate tumor growth, and improve survival in ErbB2/HER2-enriched breast cancer

et al. 2023

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Background Carbonic anhydrases catalyze CO2/HCO3– buffer reactions with implications for effective H+ mobility, pH dynamics, and cellular acid–base sensing. Yet, the integrated consequences of carbonic anhydrases for cancer and stromal cell functions, their interactions, and patient prognosis are not yet clear. Methods We combine (a) bioinformatic analyses of human proteomic data and bulk and single-cell transcriptomic data coupled to clinicopathologic and prognostic information; (b) ex vivo experimental studies of gene expression in breast tissue based on quantitative reverse transcription and polymerase chain reactions, intracellular and extracellular pH recordings based on fluorescence confocal microscopy, and immunohistochemical protein identification in human and murine breast cancer biopsies; and (c) in vivo tumor size measurements, pH-sensitive microelectrode recordings, and microdialysis-based metabolite analyses in mice with experimentally induced breast carcinomas. Results Carbonic anhydrases—particularly the extracellular isoforms CA4, CA6, CA9, CA12, and CA14—undergo potent expression changes during human and murine breast carcinogenesis. In patients with basal-like/triple-negative breast cancer, elevated expression of the extracellular carbonic anhydrases negatively predicts survival, whereas, surprisingly, the extracellular carbonic anhydrases positively predict patient survival in HER2/ErbB2-enriched breast cancer. Carbonic anhydrase inhibition attenuates cellular net acid extrusion and extracellular H+ elimination from diffusion-restricted to peripheral and well-perfused regions of human and murine breast cancer tissue. Supplied in vivo, the carbonic anhydrase inhibitor acetazolamide acidifies the microenvironment of ErbB2-induced murine breast carcinomas, limits tumor immune infiltration (CD3+ T cells, CD19+ B cells, F4/80+ macrophages), lowers inflammatory cytokine (Il1a, Il1b, Il6) and transcription factor (Nfkb1) expression, and accelerates tumor growth. Supporting the immunomodulatory influences of carbonic anhydrases, patient survival benefits associated with high extracellular carbonic anhydrase expression in HER2-enriched breast carcinomas depend on the tumor inflammatory profile. Acetazolamide lowers lactate levels in breast tissue and blood without influencing breast tumor perfusion, suggesting that carbonic anhydrase inhibition lowers fermentative glycolysis. Conclusions We conclude that carbonic anhydrases (a) elevate pH in breast carcinomas by accelerating net H+ elimination from cancer cells and across the interstitial space and (b) raise immune infiltration and inflammation in ErbB2/HER2-driven breast carcinomas, restricting tumor growth and improving patient survival.

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Section: Resultsmentioning

confidence: 99%

Carbonic anhydrases reduce the acidity of the tumor microenvironment, promote immune infiltration, decelerate tumor growth, and improve survival in ErbB2/HER2-enriched breast cancer

et al. 2023

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“…обнаружили: ацетазол амид способен воздействовать на перициты, что способствует улучшению кровотока в сетчатке [57]. В проспективных исследованиях было выявлено, что ацетазоламид увеличивает амплитуду пульсации ретинальных сосудов дозозависимым образом, уменьшая при этом индекс резистентности глазной артерии [58], внутренней сонной артерии и центральной артерии сетчатки [59] и повышает показатели ретинального кровотока, измеряемые с помощью лазерной доплеровской велосиметрии [51]. Важно, что препарат улучшает также хориоидальную гемодинамику [60].…”

Section: влияние ика на глазной кровотокunclassified

Carbonic Anhydrase Inhibitors in the Treatment of Glaucoma. Review. Part I

Курышева

2020

Oftalʹmologiâ

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“…7,8 Many AEDs including vigabatrin, carbamazepine, sodium valproate, phenytoin, and phenobarbital have been investigated and shown to decrease the cerebral blood flow in addition to the glucose metabolic rate. [9][10][11] The eye and the brain are interconnected by the carotid artery network, forming a hemodynamic continuum, 12 and various vasoactive stimuli and drugs cause similar changes in the cerebral and ocular blood flow, [13][14][15][16] indicating that the changes in cerebral circulation may develop in concert with equivalent changes in ocular blood flow. Another possible underlying mechanism in the retinal neurodegeneration process is the accompanying presence of decreased ocular vascular perfusion in epilepsy patients using AEDs.…”

Section: Introductionmentioning

confidence: 99%

Ocular hemodynamics in epileptic children treated with antiepileptic drugs

Gultutan,

Nalcacioglu,

Icoz

et al. 2023

European Journal of Ophthalmology

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Purpose To evaluate the quantitative measurements obtained for vessel density (VD) of the optic nerve head, macula, peripapillary retinal nerve fibre layer (p-RNFL) and total retinal thicknesses (Trt) by optical coherence tomography angiography (OCT-A) and the choroidal vascular structure using an image binarization method in children with epilepsy using three different antiepileptic drugs (AEDs) and to compare these measurements with healthy participants. Methods This observational, cross-sectional study included 124 patients divided into 4 groups: Group-1: patients receiving carbamazepine(n = 30), group-2: patients receiving levetiracetam (n = 31), group-3: patients receiving valproic acid (n = 32), and group 4: healthy controls (n = 31).A fully automated microstructural analysis of the VD of the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and the choriocapillaris (CC) layers and radial peripapillary capillary, and Trt, p-RNFL thickness were analyzed by using OCT-A. Enhanced depth imaging (EDI)-OCT scans of the macula were obtained and the images were binarized using the ImageJ software. Results The mean age, gender distribution and the duration of epilepsy were similar in all groups. Evaluation of the p-RNFL thickness and perifoveal Trt between the groups showed a statistically significant difference in all quadrants.The p-RNFL thickness was lower in patients receiving carbamazepine and valproic acid. The lowest values of the luminal area and choroidal vascular index (CVI) were found in patients receiving valproic acid; comparison with matched healthy controls showed statistically significant differences. Conclusion Valproic acid and carbamazepine are associated with thinning of the p-RNFL in epilepsy patients, but the macular and radial peripapillary VD were not affected.However, a reduction of choroidal vascular blood flow was found in epilepsy patients taking valproic acid.

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Acetazolamide and CO2

Cited by 36 publications

References 0 publications

Carbonic anhydrases reduce the acidity of the tumor microenvironment, promote immune infiltration, decelerate tumor growth, and improve survival in ErbB2/HER2-enriched breast cancer

Carbonic anhydrases reduce the acidity of the tumor microenvironment, promote immune infiltration, decelerate tumor growth, and improve survival in ErbB2/HER2-enriched breast cancer

Carbonic Anhydrase Inhibitors in the Treatment of Glaucoma. Review. Part I

Ocular hemodynamics in epileptic children treated with antiepileptic drugs

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