Aminoguanidine inhibits ventricular fibrosis and remodeling process in isoproterenol-induced hypertrophied rat hearts by suppressing ROS and MMPs

Arumugam, Parthasarathy; Gopi, Venkatachalam; Km, Shyamala Devi; Balaji, N Sri; Vellaichamy, Elangovan

doi:10.1016/j.lfs.2014.09.030

Cited by 25 publications

(18 citation statements)

References 58 publications

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“…The protective effect of AG in cisplatin-induced renal damage may be achieved by two mechanisms. Firstly, AG inhibits the activity of iNOS and reduces the formation of peroxynitrite (Radi 2004;Parthasarathy et al 2014). When the production of NO is decreased by the administration of AG, the source of peroxynitrite is reduced.…”

Section: Discussionmentioning

confidence: 99%

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Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats

Ilić

Stojiljković

Sokolović

et al. 2020

Can. J. Physiol. Pharmacol.

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Since cisplatin-induced nephrotoxicity has very important clinical consequences, the purpose of this study was to determine the potential protective effect of aminoguanidine on the acute kidney injury caused by cisplatin. Experiments were done on 40 Wistar rats divided into four groups. The CIS group received cisplatin in a single dose of 8 mg/kg, while the CISAG group received the same dose of cisplatin and aminoguanidine (100 mg/kg) by intraperitoneal injections. Animals in the AG group received only aminoguanidine (100 mg/kg) and those in the C group received saline. Quantitative evaluation of structural and functional alterations in the kidneys was performed by analysis of biochemical and parameters of oxidative stress and by histological and morphometric analysis of renal sections. Histological sections of kidney showed structural damage of proximal tubules and glomeruli that were induced by cisplatin. Morphometric analysis revealed statistically significant differences in the area of proximal tubules and the size and cellularity of glomeruli between the CIS and CISAG groups. Glomerular basement membrane thickness was increased in the CIS group, while aminoguanidine attenuated these changes in the CISAG group of rats. Our results suggest that aminoguanidine acts protectively and repairs structural and functional damage of kidney by engaging the existent antioxidative potential at the level of renal tissue.

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Section: Discussionmentioning

confidence: 99%

“…Aminoguanidine (AG) is an analogue of L-arginine, known as a specific inhibitor of inducible nitric oxide synthase (iNOS), a potent antioxidant and a free radical scavenger (Parthasarathy et al 2014). AG has many other activities such as inhibition of diamine oxides and preventing advanced glycosylation (Jedidi et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats

Ilić

Stojiljković

Sokolović

et al. 2020

Can. J. Physiol. Pharmacol.

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“…The cardiac mast cell induces MMP activation due to oxidative stress as well as TNF-α which causes degradation of collagen causing cardiac fibrosis in cardiac hypertrophy (Lee et al, 2010; Parthasarathy et al, 2014). ROS also have potent effects on the extracellular matrix, stimulating cardiac fibroblast proliferation and activating MMPs.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of Ulmus wallichiana Planchon in β-Adrenergic Agonist Induced Cardiac Hypertrophy

et al. 2016

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Ulmus wallichiana Planchon (Family: Ulmaceae), a traditional medicinal plant, was used in fracture healing in the folk tradition of Uttarakhand, Himalaya, India. The present study investigated the cardioprotective effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in isoprenaline (ISO) induced cardiac hypertrophy in Wistar rats. Cardiac hypertrophy was induced by ISO (5 mg/kg/day, subcutaneously) in rats. Treatment was performed by oral administration of EE and BF of U. wallichiana (500 and 50 mg/kg/day). The blood pressure (BP) and heart rate (HR) were measured by non-invasive blood pressure measurement technique. Plasma renin, Ang II, NO, and cGMP level were estimated using an ELISA kit. Angiotensin converting enzyme activity was estimated. BP and HR were significantly increased in ISO group (130.33 ± 1.67 mmHg vs. 111.78 ± 1.62 mmHg, p < 0.001 and 450.51 ± 4.90 beats/min vs. 347.82 ± 6.91 beats/min, respectively, p < 0.001). The BP and HR were significantly reduced (EE: 117.53 ± 2.27 mmHg vs. 130.33 ± 1.67 mmHg, p < 0.001, BF: 119.74 ± 3.32 mmHg vs. 130.33 ± 1.67 mmHg, p < 0.001); HR: (EE: 390.22 ± 8.24 beats/min vs. 450.51 ± 4.90 beats/min, p < 0.001, BF: 345.38 ± 6.79 beats/min vs. 450.51 ± 4.90 beats/min, p < 0.001) after the treatment of EE and BF of U. wallichiana, respectively. Plasma renin, Ang II, ACE activity was decreased and NO, cGMP level were increased. The EE and BF of U. wallichiana down regulated the expression of ANP, BNP, TNF-α, IL-6, MMP9, β1-AR, TGFβ1 and up regulated NOS3, ACE2 and Mas expression level, respectively. Thus, this study demonstrated that U. wallichiana has cardioprotective effect against ISO induced cardiac hypertrophy.

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“…Considering that AG has ROS-detoxification activity (27)(28)(29), and that ROS lead to ECM accumulation in diabetes (30), we investigated the role of AG in AGE signaling in primary myofibroblasts. Primary myofibroblasts from neonatal rats were exposed for 48 h to extended high insulin (0-50 nM) and high glucose (0-17.5 mM) levels to induce the impairment of insulin signaling and to desensitize glucose transport (HIG AG reduced phosphorylation of ERK1/2 and SMAD2/3 but not AKT1/2/3 473 Ser, AKT1/2/3 308 Thr or STAT3 705 Tyr in primary rat myofibroblasts (Fig.…”

Section: Ag Reduces Oxidation-associated Collagen Type I Expression Tmentioning

confidence: 99%

Aminoguanidine reduces diabetes‑associated cardiac fibrosis

et al. 2019

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Aminoguanidine (AG) inhibits advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP) accumulated as a result of excessive oxidative stress in diabetes. However, the molecular mechanism by which AG reduces AGE-associated damage in diabetes is not well understood. Thus, we investigated whether AG supplementation mitigates oxidative-associated cardiac fibrosis in rats with type 2 diabetes mellitus (T2DM). Forty-five male Wistar rats were divided into three groups: Control, T2DM and T2DM+AG. Rats were fed with a high-fat, high-carbohydrate diet (HFCD) for 2 weeks and rendered diabetic using low-dose streptozotocin (STZ) (20 mg/kg), and one group was treated with AG (20 mg/kg) up to 25 weeks. In vitro experiments were performed in primary rat myofibroblasts to confirm the antioxidant and antifibrotic effects of AG and to determine if blocking the receptor for AGEs (RAGE) prevents the fibrogenic response in myofibroblasts. Diabetic rats exhibited an increase in cardiac fibrosis resulting from HFCD and STZ injections. By contrast, AG treatment significantly reduced cardiac fibrosis, α-smooth muscle actin (αSMA) and oxidative-associated Nox4 and Nos2 mRNA expression. In vitro challenge of myofibroblasts with AG under T2DM conditions reduced intra-and extracellular collagen type I expression and Pdgfb, Tgfβ1 and Col1a1 mRNAs, albeit with similar expression of Tnfα and Il6 mRNAs. This was accompanied by reduced phosphorylation of ERK1/2 and SMAD2/3 but not of AKT1/2/3 and STAT pathways. RAGE blockade further attenuated collagen type I expression in AG-treated myofibroblasts. Thus, AG reduces oxidative stress-associated cardiac fibrosis by reducing pERK1/2, pSMAD2/3 and collagen type I expression via AGE/RAGE signaling in T2DM.

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Aminoguanidine inhibits ventricular fibrosis and remodeling process in isoproterenol-induced hypertrophied rat hearts by suppressing ROS and MMPs

Cited by 25 publications

References 58 publications

Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats

Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats

Cardioprotective Effect of Ulmus wallichiana Planchon in β-Adrenergic Agonist Induced Cardiac Hypertrophy

Aminoguanidine reduces diabetes‑associated cardiac fibrosis

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