The influence of sulindac on diabetic cardiomyopathy: A non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats

Krishna, Kota Murali; Gopal, Gopisetty S; Chitrapu, Ravi Venkatachelam; Madan, K.; Veeravalli, Krishna Kumar; Prakash, G. Jaya; Akula, Annapurna

doi:10.1016/j.vph.2005.02.012

Cited by 10 publications

(7 citation statements)

References 38 publications

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“…Cardiac dysfunction is the most common serious complication of diabetes mellitus and has become one of the leading causes of the increased mortality in both Type 1 and Type 2 diabetes. A streptozotocin (STZ)-induced type 1 diabetic rat has been used as an animal model for the investigation of pharmacological interventions and also for the study of diabetic complications including diabetes-induced cardiac dysfunction (Krishna et al 2005, Naowaboot et al 2009). Clinically, cardiac dysfunction may occur without major vascular lesions, indicating a primary role for the direct effects of diabetes on cardiomyocytes (Trost & LeWinter 2001, Dyntar et al 2006.…”

Section: Introductionmentioning

confidence: 99%

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Semaming¹,

Kumfu²,

Pannangpetch³

et al. 2014

Journal of Endocrinology

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Oxidative stress has been shown to play an important role in the pathogenesis of diabetesinduced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague-Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50 mg/kg per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c. injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA, 100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio in T1DM rats. Moreover, all treatments significantly decreased plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be helpful for the prevention and alleviation of cardiovascular complications in T1DM.

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Section: Introductionmentioning

confidence: 99%

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Semaming¹,

Kumfu²,

Pannangpetch³

et al. 2014

Journal of Endocrinology

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“…Sulindac (SLD), a widely used non-steroidal anti-inflammatory drug (NSAID) that is a potent non-selective inhibitor of cyclooxygenases (COXs) [1], has shown convincing evidence of beneficial pharmacological effects on Type 2 diabetic complications in animal experiments and in clinical trials [2][3][4][5][6][7][8][9]. The inhibition of aldose reductase (AR, EC 1.1.1.21) by SLD has been proposed to play an important role in its diabetic benefits [3,4,7,10].…”

Section: Introductionmentioning

confidence: 99%

“…In vitro studies have shown that SLD exhibits the highest inhibitory activity towards AR among all tested NASIDs [17]. In addition, in vivo experiments have demonstrated that SLD significantly suppresses sorbitol accumulation in red blood cells and in sciatic nerves, and reduces fructose and sorbitol dehydrogenase levels in diabetic rat models [3,4,10].…”

Section: Introductionmentioning

confidence: 99%

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

et al. 2011

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Edited by Stuart FergusonKeywords: Sulindac Metabolite Tolmetin Aldose reductase Crystal structure a b s t r a c t Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals that p-p stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.

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“…Echocardiography is the most widely used low‐cost imaging tool for the evaluation of patients with coronary artery disease and LV dysfunction 31 . However, until recently, it has been very difficult to estimate myocardial perfusion in small animals using conventional echocardiography 32 .…”

Section: Discussionmentioning

confidence: 99%

INHIBITION OF LEFT VENTRICULAR REMODELLING IN SPONTANEOUSLY HYPERTENSIVE RATS by G_αq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 IS NOT ENTIRELY DEPENDENT ON BLOOD PRESSURE

Wang

Zhang

Cheng

et al. 2008

Clin Exp Pharma Physio

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1. The present study investigated the therapeutic effects of both single and combination treatment with Yunke (technetium-99 conjugated with methylene diphosphonate; (99)Tc-MDP) and colloidal chromic phosphate (32)P (phosphonium-32) in rats with adjuvant arthritis (AA). 2. Rats were randomly allocated to one of five groups: (i) normal control group (sham operated and treated with normal saline); (ii) AA control group (arthritis induced with adjuvant and treated with normal saline); (iii) (32)P colloid group (arthritis induced with adjuvant and treated with a single intra-articular injection of colloidal chromic phosphate phosphonium-32 (0.02 mCi) and i.p. injections of normal saline every other day); (iv) Yunke group (arthritis induced with adjuvant and treated with i.p. Yunke (2.5 x 10(-3) microg/kg) every other day and single intra-articular injection of normal saline); and (v) combination group (arthritis induced with adjuvant and treated with a combination of both therapies). 3. The left-to-right diameter (LRD) of the left hind ankle, serum levels of tumour necrosis factor (TNF) and interleukin (IL)-1b and histological sections of the ankle joints were examined at different time points. 4. The LRD of the left hind ankle was smaller for the combination group compared with (32)P colloid alone at Week 4 (7.11 +/- 0.28 vs 7.57 +/- 0.24 mm, respectively; P < 0.001). The combination treatment was more effective than (32)P colloid alone in decreasing serum TNF (1.614 +/- 0.368 vs 1.977 +/- 0.255 ng/mL, respectively; P = 0.002 for Week 4) and IL-1b (0.271 +/- 0.027 vs 0.308 +/- 0.020 ng/mL, respectively for Week 4; 0.209 +/- 0.023 vs 0.255 +/- 0.016 ng/mL, respectively for Week 6; both P = 0.001). Histologically, the combination group exhibited less synovium proliferation compared with Yunke treatment alone and decreased inflammatory cell infiltration compared with (32)P colloid alone. 5. In conclusion, the combination of Yunke and (32)P colloid is more effective in the treatment of AA in rats compared with Yunke or (32)P colloid alone.

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The influence of sulindac on diabetic cardiomyopathy: A non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats

Cited by 10 publications

References 38 publications

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

INHIBITION OF LEFT VENTRICULAR REMODELLING IN SPONTANEOUSLY HYPERTENSIVE RATS by G_αq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 IS NOT ENTIRELY DEPENDENT ON BLOOD PRESSURE

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The influence of sulindac on diabetic cardiomyopathy: A non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats

Cited by 10 publications

References 38 publications

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase

INHIBITION OF LEFT VENTRICULAR REMODELLING IN SPONTANEOUSLY HYPERTENSIVE RATS by Gαq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 IS NOT ENTIRELY DEPENDENT ON BLOOD PRESSURE

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Resources

About

INHIBITION OF LEFT VENTRICULAR REMODELLING IN SPONTANEOUSLY HYPERTENSIVE RATS by G_αq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 IS NOT ENTIRELY DEPENDENT ON BLOOD PRESSURE