Implantation of disulfiram in rats

Hellström, Ewa; Tottmar, Olof; Fried, Rainer

doi:10.1016/s0091-3057(80)80012-8

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Disulfiram treatment slightly but significantly lowered systolic blood pressure in Ang II-infused, ApoE deficient mice. Consistent with the present study, the short- or long-term disulfiram treatment has been reported to slightly or moderately lower systolic blood pressure in people and rodents [ 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Thus, the question is whether reduced blood pressure played a role in AAA attenuation by disulfiram.…”

Section: Discussionsupporting

confidence: 92%

Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms

et al. 2023

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Background: Gasdermin D, a molecule downstream of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing inflammasome, forms the membrane pore for the secretion of interleukin (IL)-1β and IL-18, and also mediates pyroptosis. This study was to explore the influence of treatment with disulfiram, a small molecule inhibitor to gasdermin D, on the formation and progression of experimental abdominal aortic aneurysms (AAA). Methods: AAAs were induced in 10-week-old male apolipoprotein E deficient mice by subcutaneous infusion of angiotensin II (1000 ng/min/kg body weight) for 28 days via osmotic minipumps. Three days prior to angiotensin II infusion, disulfiram (50 mg/kg) or an equal volume of saline as the vehicle control was administered daily via oral gavage. The influence on experimental AAAs was analyzed by serial measurements of aortic diameters via ultrasonography, grading AAA severity and histopathology at sacrifice. Serum IL-1β and IL-18 levels, systolic blood pressure, total cholesterol, and triglyceride were also measured. Additional experiments assayed the influences on the cell viability and IL-1β secretion of in vitro activated macrophages. Results: Disulfiram significantly reduced the enlargement, incidence, and severity of angiotensin II-induced experimental AAAs with attenuation of medial elastin breaks, mural macrophage accumulation, and systolic blood pressure. The AAA suppression was also associated with reduced systemic levels of IL-1β but not IL-18. However, disulfiram treatment had no impact on body weight gain and lipid levels in aneurysmal mice. Additionally, disulfiram treatment also markedly reduced the secretion of IL-1β from activated macrophages with a limited effect on cell viability in vitro. Conclusions: Gasdermin D inhibition by disulfiram attenuated angiotensin II-induced experimental AAAs with reduced systemic IL-1β levels and in vitro activated macrophage IL-1β secretion. Our study suggests that pharmacological gasdermin D inhibition may have translational potential for limiting clinical AAA progression.

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Section: Discussionsupporting

confidence: 92%

Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms

et al. 2023

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“…This method could not be used to record the activity at low substrate concentrations (<20 p~) of acetaldehyde and DOPAL because of the low activity and the presence of interfering blank reactions. In this case, the activity was determined as the rate of disappearance of the substrate, as described in detail by Hellstrom et al (1980). The reaction rates were linear for at least 15 min and proportional to the amount of sample added.…”

Section: Enzyme Assaysmentioning

confidence: 99%

Aldehyde Dehydrogenases in Rat Brain. Subcellular Distribution and Properties

Pettersson

Tottmar

1982

Journal of Neurochemistry

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Kinetic studies suggested the presence of several forms of NAD-dependent aldehyde dehydrogenase (ALDH) in rat brain. A subcellular distribution study showed that low- and high-Km activities with acetaldehyde as well as the substrate-specific enzyme succinate semialdehyde dehydrogenase were located mainly in the mitochondrial compartment. The low-Km activity was also present in the cytosol (less than 20%). The low-Km activity in the homogenate was only 10-15% of the total activity with acetaldehyde as the substrate. Two Km values were obtained with both acetaldehyde (0.2 and 2000 microM) and 3,4-dihydroxyphenylacetaldehyde (DOPAL) (0.3 and 31 microM), and one Km value with succinate semialdehyde (5 microM). The main part of the aldehyde dehydrogenase activities with acetaldehyde, DOPAL, and succinate semialdehyde, but only little activity of the marker enzyme for the outer membrane (monoamine oxidase, MAO), was released from a purified mitochondrial fraction subjected to sonication. Only small amounts of the ALDH activities were released from mitochondria subjected to swelling in a hypotonic buffer, whereas the main part of the marker enzyme for the intermembrane space (adenylate kinase) was released. These results indicate that the ALDH activities with acetaldehyde, DOPAL and succinate semialdehyde are located in the matrix compartment. The low-Km activity with acetaldehyde and DOPAL, but not the high-Km activities and succinate semialdehyde dehydrogenase, was markedly stimulated by Mg2+ and Ca2+ in phosphate buffer. The low- and high-Km activities with acetaldehyde showed different pH optima in pyrophosphate buffer.

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Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain

Hellström

Tottmar

1982

Biochemical Pharmacology

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Implantation of disulfiram in rats

Cited by 4 publications

References 38 publications

Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms

Pharmacological Inhibition of Gasdermin D Suppresses Angiotensin II-Induced Experimental Abdominal Aortic Aneurysms

Aldehyde Dehydrogenases in Rat Brain. Subcellular Distribution and Properties

Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain

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