<i>N</i>-acetylcysteine attenuates PKCβ<sub>2</sub>overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats

Xia, Zhengyuan; Kuo, Kuo‐Hsing; Nagareddy, Prabhakara R; Wang, Fang; Guo, Zhixin; Guo, Tianhai; Jiang, Jihong; McNeill, John H.

doi:10.1016/j.cardiores.2006.11.033

Cited by 95 publications

(87 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enhanced MDA and ROS were accompanied by compromised Mn-SOD activity, GSH content and total antioxidant concentration. These findings are similar to those reported in the previous literature (22,30), indicating increased levels of oxidative stress in diabetic rats.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats

Wang

Hao

et al. 2010

Mol Med

116

View full text Add to dashboard Cite

Left ventricular (LV) dysfunction is a common comorbidity in diabetic patients, although the molecular mechanisms underlying this cardiomyopathic feature are not completely understood. Aldehyde dehydrogenase 2 (ALDH2) has been considered a key cardioprotective enzyme susceptible to oxidative inactivation. We hypothesized that hyperglycemia-induced oxidative stress would influence ALDH2 activity, and ALDH2 inhibition would lead to cardiac functional alterations in diabetic rats. Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin. Rats were divided randomly into four groups: control, untreated diabetic, diabetic treated with N-acetylcysteine (NAC) and diabetic treated with a-lipoic acid (α-LA). Cardiac contractile function, oxidative stress markers and reactive oxygen species (ROS) levels were assessed. ALDH2 activity and expression also were determined. The role of ALDH2 activity in change in hyperglycemia-induced mitochondrial membrane potential (Δψ) was tested in cultured neonatal cardiomyocytes. Myocardial MDA content and ROS were significantly higher in diabetic rats than in controls, whereas GSH content and Mn-SOD activity were decreased in diabetic rats. Compared with controls, diabetic rats exhibited significant reduction in LV ejection fraction and fractional shortening, accompanied by decreases in ALDH2 activity and expression. NAC and α-LA attenuated these changes. Mitochondrial Δψ was decreased greatly with hyperglycemia treatment, and high glucose combined with ALDH2 inhibition with daidzin further decreased Δψ. The ALDH2 activity can be regulated by oxidative stress in the diabetic rat heart. ALDH2 inhibition may be associated with LV reduced contractility, and mitochondrial impairment aggravated by ALDH2 inhibition might reflect an underlying mechanism which causes cardiac dysfunction in diabetic rats.

show abstract

Section: Discussionsupporting

confidence: 93%

“…One wk after diabetes induction, NAC and α-LA were administered to the diabetic treated groups by oral gavage for eight wks. The concentrations of NAC and α-LA were adjusted for a daily intake of 1.4 g/kg and 60 mg/kg, respectively, according to previous studies (22,23).…”

Section: Experimental Protocolmentioning

confidence: 99%

Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats

Wang

Hao

et al. 2010

Mol Med

116

View full text Add to dashboard Cite

show abstract

“…Taking this into consideration, NAC treatment aiming at reduced MDA levels represents a promising therapeutic opportunity. But, in spite of many reports reassuring its beneficial effect on oxidative stress (22,(32)(33)(34), our study has failed to reduce MDA concentrations. We do not have a clear understanding about the reason why NAC treatment did not restore normal MDA levels, but we hypothesize that this failure could be related to NAC dose or late onset of NAC treatment.…”

Section: Discussioncontrasting

confidence: 63%

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats

Capellini

Baldo

Celotto

et al. 2010

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

Objectives:To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Methods: Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/ nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. Results: MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. Conclusions: NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress. Arq Bras Endocrinol Metab. 2010;54(6):530-9 Keywords Oxidative stress; diabetes; nitric oxide; vascular function; N-acetylcysteine RESUMO Objetivos: Verificar se um modelo experimental de diabetes por aloxana promove estresse oxidativo, reduz a disponibilidade de óxido nítrico e causa disfunção vascular, e avaliar o efeito da N-acetilcisteína (NAC) nesses parâmetros. Métodos: Ratos diabéticos por aloxana foram tratados com NAC por quatro semanas. Níveis plasmáticos de malondialdeído (MDA) e nitrito/ nitrato (NOx), imunomarcação para óxido nítrico sintase endotelial e induzida (eNOS e iNOS) e reatividade vascular da aorta foram comparados entre ratos diabéticos (D), diabéticos tratados (TD) e controles (C). Resultados: O MDA aumentou nos grupos D e TD. O NOx não diferiu entre os grupos. A marcação da eNOS no endotélio reduziu e a da iNOS na adventícia aumentou nos grupos D e TD. A responsividade dos anéis vasculares à acetilcolina, nitroprussiato de sódio e fenilefrina não diferiu entre os grupos. Conclusões: A NAC não teve efeito sobre os parâmetros avaliados. Esse modelo experimental não promoveu disfunção vascular apesar do desenvolvimento de estresse oxidativo. Arq Bras Endocrinol Metab. 2010;54(6):530-9 Descritores

show abstract

“…Of these, 8-iso-prostaglandin F 2 (8-iso PGF 2 ) has recently been shown to be a specific and sensitive quantitative index of oxidative stress in vivo (Delanty et al, 1997). We and others have found that in STZ rats with type 1 diabetic cardiomyopathy, LV levels of 8-iso PGF 2 were significantly increased in vivo (Hamblin et al 2007a(Hamblin et al , 2007bXia et al, 2007). Collectively, these experimental animal studies demonstrate that diabetic cardiomyopathy is associated with greater myocardial oxidative stress burden.…”

Section: Myocardial Oxidative Stress: a Key Contributor To Diabetic Csupporting

confidence: 51%

Diabetic Cardiomyopathy: Cardiac Changes, Pathophysiological Mechanisms, Biologic Markers, and the Available Therapeutic Armamentarium

Hill¹

2012

Cardiomyopathies - From Basic Research to Clinical Management

View full text Add to dashboard Cite

N-acetylcysteine attenuates PKCβ₂overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats

Abstract: The results suggest that PKCbeta(2) overexpression represents a mechanism causing hyperglycemia-mediated myocardial hypertrophy, which can be prevented by the antioxidant N-acetylcysteine.

Cited by 95 publications

References 39 publications

Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats

Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats

Diabetic Cardiomyopathy: Cardiac Changes, Pathophysiological Mechanisms, Biologic Markers, and the Available Therapeutic Armamentarium

Contact Info

Product

Resources

About

N-acetylcysteine attenuates PKCβ2overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats

Abstract: The results suggest that PKCbeta(2) overexpression represents a mechanism causing hyperglycemia-mediated myocardial hypertrophy, which can be prevented by the antioxidant N-acetylcysteine.

Cited by 95 publications

References 39 publications

Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats

Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats

Diabetic Cardiomyopathy: Cardiac Changes, Pathophysiological Mechanisms, Biologic Markers, and the Available Therapeutic Armamentarium

Contact Info

Product

Resources

About

N-acetylcysteine attenuates PKCβ₂overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats