Disulfiram Augments Oxidative Stress in Rat Brain following Bilateral Carotid Artery Occlusion

Ningaraj, Nagendra S.; Rao, Mamatha K.

doi:10.1159/000025335

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…Recently, the FDA-approved drug disulfiram was demonstrated to inhibit pyroptosis by interfering with the pore-forming activity of cleaved GSDMD [67]. Although, to the best of our current knowledge, disulfiram has not been investigated in AKI models, it has been demonstrated to augment oxidative stress in rat brains following bilateral carotid artery occlusion [68]. Our data that point to a non-cell autonomous tissue-protective function of GSDMD are in line with those discoveries.…”

Section: Discussionsupporting

confidence: 87%

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

et al. 2022

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Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD-protein expression in whole kidney lysates increased during the first 84 h following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD-protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea, and serum creatinine. This hypersensitivity was reversed by a combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI.

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Section: Discussionsupporting

confidence: 87%

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

et al. 2022

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“…Several studies have suggested that oxidative stress plays a role in ischaemia-related brain damage. 15,16 Further observations regarding the occurrence of ischaemic stroke in SHRSP are of great interest because increased oxidative stress may directly affect brain damage in SHRSP.…”

Section: Resultsmentioning

confidence: 99%

Increased Oxidative Dna Damage in Stroke‐prone Spontaneously Hypertensive Rats

Negishi¹,

Ikeda

Sagara³

et al. 1999

Clin Exp Pharma Physio

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1. The amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of the total systemic oxidative stress in vivo, in stroke-prone spontaneously hypertensive rats (SHRSP) was not different from that in control normotensive Wistar-Kyoto (WKY) rats at 6 weeks of age, but became higher than control values after the development of severe hypertension at 14-17 weeks of age. 2. The amount of urinary 8-OHdG was not significantly different between SHRSP treated with anti-hypertensive agents and those not treated at 14 weeks of age. 3. Stroke-prone spontaneously hypertensive rats were exposed to DNA damage by oxidative stress at the early stage when they developed severe hypertension, but this increase in DNA damage was not the secondary effect of hypertension.

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“…Recently, the FDA-approved drug disulfiram was demonstrated to inhibit pyroptosis by interfering with the pore forming activity of cleaved GSDMD 62 . Although to the best of our current knowledge, disulfiram has not been investigated in AKI models, it has been demonstrated to augment oxidative stress in rat brain following bilateral carotid artery occlusion 63 . Our data that point to a non-cell autonomous tissue protective function of GSDMD are in line with those discoveries.…”

Section: Discussionmentioning

confidence: 99%

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

Linkermann

Tonnus

Belavgeni

et al. 2022

Preprint

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Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD protein expression in whole kidney lysates increased during the first 84 hours following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea and serum creatinine. This hypersensitivity was reversed by combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI.

show abstract

Disulfiram Augments Oxidative Stress in Rat Brain following Bilateral Carotid Artery Occlusion

Cited by 3 publications

References 24 publications

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

Increased Oxidative Dna Damage in Stroke‐prone Spontaneously Hypertensive Rats

Gasdermin D-deficient mice are hypersensitive to acute kidney injury

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