[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury

Objective: To investigate the effect Alda-1, aldehyde dehydrogenase-2 (ALDH2) agonist, on renal functions following ischaemia–reperfusion (IRI) injury. IRI induces the production of aldehydes, which are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2 agonist and its protec...

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Autores principales:	Fayez Hammad, Suhail Al-Salam, Loay Lubbad
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2018
Materias:	Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/c3707300053e42bba90b456e24a114e5
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spelling	oai:doaj.org-article:c3707300053e42bba90b456e24a114e52021-12-02T12:07:16Z[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury2090-598X10.1016/j.aju.2018.10.012https://doaj.org/article/c3707300053e42bba90b456e24a114e52018-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2090598X18301062https://doaj.org/toc/2090-598XObjective: To investigate the effect Alda-1, aldehyde dehydrogenase-2 (ALDH2) agonist, on renal functions following ischaemia–reperfusion (IRI) injury. IRI induces the production of aldehydes, which are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2 agonist and its protective effect has been demonstrated in several conditions; however, the effect of Alda-1 on the kidney or on renal IRI has not been investigated. Methods: We investigated the effect of Alda-1 on renal dysfunction following IRI. Wistar rats underwent left IRI for 40 min. Group-Alda (n = 11) received Alda-1 starting 24 h before IRI and continued for 7 days and then renal functions were measured. Group-Vx (n = 11) underwent the same protocol but received only the dissolvent. Results: Alda-1 did not affect renal blood flow or glomerular filtration rate in the left ischaemic kidney in Group-Alda compared to the Group-Vx [mean (SD) 3.05 (0.50) vs 3.53 (0.70) mL/min, and 0.40 (0.06) vs 0.51 (0.08) mL/min/1.73 m2, respectively; both P > 0.05]. However, left renal fractional sodium excretion was significantly worse in Group-Alda [mean (SD) 2.80 (0.43) vs 1.37 (0.36)%; P = 0.02). Alda-1 also adversely affected the gene expressions of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) [mean (SD) 217 (38) vs 99 (13) and 49 (13) vs 20 (5), respectively; both P < 0.05] and the alterations in tumour necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), plasminogen activator inhibitor 1 (PAI-1), fibronectin 1 (Fn1) and p53 [mean (SD) 4.4 (0.9) vs 2.1 (0.3), 1.5 (0.1) vs 1.1 (0.1), 30.0 (2.7) vs 11.7 (2.3), 3.6 (0.4) vs 2.1 (0.2) and 1.3 (0.1) vs 0.9 (0.07), respectively; all P ⩽ 0.05]. This was associated with intratubular crystal deposition suggestive of crystalline nephropathy. Conclusion: Alda-1 exacerbated the IRI-induced renal tubular dysfunction and alterations in pro-inflammatory and pro-fibrotic cytokines, which appears be due to crystalline nephropathy. Extreme caution should be taken when administering ALda-1 or other potentially crystal-forming medications to subjects with underlying kidney disease.Fayez HammadSuhail Al-SalamLoay LubbadTaylor & Francis GrouparticleDiseases of the genitourinary system. UrologyRC870-923ENArab Journal of Urology, Vol 16, Iss , Pp S29- (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the genitourinary system. Urology RC870-923
spellingShingle	Diseases of the genitourinary system. Urology RC870-923 Fayez Hammad Suhail Al-Salam Loay Lubbad [59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
description	Objective: To investigate the effect Alda-1, aldehyde dehydrogenase-2 (ALDH2) agonist, on renal functions following ischaemia–reperfusion (IRI) injury. IRI induces the production of aldehydes, which are detoxified by aldehyde dehydrogenases (ALDHs). Alda-1 is a selective ALDH2 agonist and its protective effect has been demonstrated in several conditions; however, the effect of Alda-1 on the kidney or on renal IRI has not been investigated. Methods: We investigated the effect of Alda-1 on renal dysfunction following IRI. Wistar rats underwent left IRI for 40 min. Group-Alda (n = 11) received Alda-1 starting 24 h before IRI and continued for 7 days and then renal functions were measured. Group-Vx (n = 11) underwent the same protocol but received only the dissolvent. Results: Alda-1 did not affect renal blood flow or glomerular filtration rate in the left ischaemic kidney in Group-Alda compared to the Group-Vx [mean (SD) 3.05 (0.50) vs 3.53 (0.70) mL/min, and 0.40 (0.06) vs 0.51 (0.08) mL/min/1.73 m2, respectively; both P > 0.05]. However, left renal fractional sodium excretion was significantly worse in Group-Alda [mean (SD) 2.80 (0.43) vs 1.37 (0.36)%; P = 0.02). Alda-1 also adversely affected the gene expressions of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) [mean (SD) 217 (38) vs 99 (13) and 49 (13) vs 20 (5), respectively; both P < 0.05] and the alterations in tumour necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), plasminogen activator inhibitor 1 (PAI-1), fibronectin 1 (Fn1) and p53 [mean (SD) 4.4 (0.9) vs 2.1 (0.3), 1.5 (0.1) vs 1.1 (0.1), 30.0 (2.7) vs 11.7 (2.3), 3.6 (0.4) vs 2.1 (0.2) and 1.3 (0.1) vs 0.9 (0.07), respectively; all P ⩽ 0.05]. This was associated with intratubular crystal deposition suggestive of crystalline nephropathy. Conclusion: Alda-1 exacerbated the IRI-induced renal tubular dysfunction and alterations in pro-inflammatory and pro-fibrotic cytokines, which appears be due to crystalline nephropathy. Extreme caution should be taken when administering ALda-1 or other potentially crystal-forming medications to subjects with underlying kidney disease.
format	article
author	Fayez Hammad Suhail Al-Salam Loay Lubbad
author_facet	Fayez Hammad Suhail Al-Salam Loay Lubbad
author_sort	Fayez Hammad
title	[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
title_short	[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
title_full	[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
title_fullStr	[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
title_full_unstemmed	[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
title_sort	[59] the effect of alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury
publisher	Taylor & Francis Group
publishDate	2018
url	https://doaj.org/article/c3707300053e42bba90b456e24a114e5
work_keys_str_mv	AT fayezhammad 59theeffectofalda1aldehydedehydrogenase2agonistontherenalfunctionsfollowingischaemiareperfusioninjury AT suhailalsalam 59theeffectofalda1aldehydedehydrogenase2agonistontherenalfunctionsfollowingischaemiareperfusioninjury AT loaylubbad 59theeffectofalda1aldehydedehydrogenase2agonistontherenalfunctionsfollowingischaemiareperfusioninjury
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[59] The effect of Alda-1, aldehyde dehydrogenase-2 agonist, on the renal functions following ischaemia–reperfusion injury

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