Effects of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats

Eur J Clin Invest 2010; 40 (11): 1002–1010 Background  We compared the haemodynamic and metabolic effects of acetyl‐L‐carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase‐1 inhibitor) in streptozotocin‐induced diabetes in male Wistar rats. Materials and me...

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Veröffentlicht in:European journal of clinical investigation 2010-11, Vol.40 (11), p.1002-1010
Hauptverfasser: Chang, Kuo-Chu, Tseng, Chuen-Den, Lu, Shao-Chun, Liang, Jin-Tung, Wu, Ming-Shiou, Tsai, Ming-Shian, Hsu, Kwan-Lih
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container_end_page 1010
container_issue 11
container_start_page 1002
container_title European journal of clinical investigation
container_volume 40
creator Chang, Kuo-Chu
Tseng, Chuen-Den
Lu, Shao-Chun
Liang, Jin-Tung
Wu, Ming-Shiou
Tsai, Ming-Shian
Hsu, Kwan-Lih
description Eur J Clin Invest 2010; 40 (11): 1002–1010 Background  We compared the haemodynamic and metabolic effects of acetyl‐L‐carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase‐1 inhibitor) in streptozotocin‐induced diabetes in male Wistar rats. Materials and methods  Diabetes was induced by a single tail vein injection of 55 mg kg−1 streptozotocin. The diabetic animals daily treated with either acetyl‐L‐carnitine (150 mg kg−1 in drinking water) or oxfenicine (150 mg kg−1 by oral gavage) for 8 weeks,were compared with the untreated age‐matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. Results  Oxfenicine, but not acetyl‐L‐carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl‐L‐carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl‐L‐carnitine may attenuate the diabetes‐induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA/TBARS content in plasma and aortic walls in diabetes. Acetyl‐L‐carnitine therapy also prevented the diabetes‐related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Conclusion  Acetyl‐L‐carnitine, but not oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly through its decrease of lipid oxidation‐derived MDA/TBARS in the rats with insulin deficiency.
doi_str_mv 10.1111/j.1365-2362.2010.02358.x
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Materials and methods  Diabetes was induced by a single tail vein injection of 55 mg kg−1 streptozotocin. The diabetic animals daily treated with either acetyl‐L‐carnitine (150 mg kg−1 in drinking water) or oxfenicine (150 mg kg−1 by oral gavage) for 8 weeks,were compared with the untreated age‐matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. Results  Oxfenicine, but not acetyl‐L‐carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl‐L‐carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl‐L‐carnitine may attenuate the diabetes‐induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA/TBARS content in plasma and aortic walls in diabetes. Acetyl‐L‐carnitine therapy also prevented the diabetes‐related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Conclusion  Acetyl‐L‐carnitine, but not oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly through its decrease of lipid oxidation‐derived MDA/TBARS in the rats with insulin deficiency.</description><identifier>ISSN: 0014-2972</identifier><identifier>EISSN: 1365-2362</identifier><identifier>DOI: 10.1111/j.1365-2362.2010.02358.x</identifier><identifier>PMID: 20678118</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Acetyl-L-carnitine ; Acetylcarnitine - therapeutic use ; Analysis of Variance ; Animals ; Aorta - drug effects ; aortic input impedance ; Biological and medical sciences ; Carnitine O-Palmitoyltransferase - antagonists &amp; inhibitors ; Carnitine O-Palmitoyltransferase - therapeutic use ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Enzyme Inhibitors - therapeutic use ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; free fatty acids ; General aspects ; Male ; malondialdehyde ; Medical sciences ; oxfenicine ; Rats ; Rats, Wistar ; streptozotocin-diabetic rats ; Vitamin B Complex - therapeutic use</subject><ispartof>European journal of clinical investigation, 2010-11, Vol.40 (11), p.1002-1010</ispartof><rights>2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation</rights><rights>2015 INIST-CNRS</rights><rights>2010 The Authors. 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Materials and methods  Diabetes was induced by a single tail vein injection of 55 mg kg−1 streptozotocin. The diabetic animals daily treated with either acetyl‐L‐carnitine (150 mg kg−1 in drinking water) or oxfenicine (150 mg kg−1 by oral gavage) for 8 weeks,were compared with the untreated age‐matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. Results  Oxfenicine, but not acetyl‐L‐carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl‐L‐carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl‐L‐carnitine may attenuate the diabetes‐induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA/TBARS content in plasma and aortic walls in diabetes. Acetyl‐L‐carnitine therapy also prevented the diabetes‐related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. 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Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>free fatty acids</subject><subject>General aspects</subject><subject>Male</subject><subject>malondialdehyde</subject><subject>Medical sciences</subject><subject>oxfenicine</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>streptozotocin-diabetic rats</subject><subject>Vitamin B Complex - therapeutic use</subject><issn>0014-2972</issn><issn>1365-2362</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtvEzEURi1ERdPCX0DeIFaT-jF-zIJFFUJbNS0sglhajudacjrxtLYjkn_PDEnDFm_8Ot_19UEIUzKlw7haTymXomJcsikjwylhXOjp7g2anC7eogkhtK5Yo9g5ush5TQjRlLN36JwRqTSleoJ-zL0HVzLuPbYOyr6rFpWzKYYSImAbW9zvPMTgxm0fse1TsTiX4H2EnHGIuA12BSU4nGzJ79GZt12GD8f5Ev38Nl_ObqvF95u72fVQvOZSV05LJcGBWrnGu6ammoqGEQeCD3-pOYFWe231qmm1oopYwl2tGqFdI7WXjl-iz4e6z6l_2UIuZhOyg66zEfptNkpyJoRizUDqA-lSn3MCb55T2Ni0N5SYUadZm9GaGa2ZUaf5q9PshujH4yPb1QbaU_DV3wB8OgI2O9v5ZKML-R_HmdZEjD18OXC_Qwf7_27AzGd342rIV4d8yAV2p7xNT0YqroT59Xhj2MMjXSyXX809_wP8PJ5j</recordid><startdate>201011</startdate><enddate>201011</enddate><creator>Chang, Kuo-Chu</creator><creator>Tseng, Chuen-Den</creator><creator>Lu, Shao-Chun</creator><creator>Liang, Jin-Tung</creator><creator>Wu, Ming-Shiou</creator><creator>Tsai, Ming-Shian</creator><creator>Hsu, Kwan-Lih</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201011</creationdate><title>Effects of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats</title><author>Chang, Kuo-Chu ; Tseng, Chuen-Den ; Lu, Shao-Chun ; Liang, Jin-Tung ; Wu, Ming-Shiou ; Tsai, Ming-Shian ; Hsu, Kwan-Lih</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4368-c8676ece7bc9fc941815920ce53023430ed8f8a8b9d87170a03c47958c968f6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acetyl-L-carnitine</topic><topic>Acetylcarnitine - therapeutic use</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>aortic input impedance</topic><topic>Biological and medical sciences</topic><topic>Carnitine O-Palmitoyltransferase - antagonists &amp; inhibitors</topic><topic>Carnitine O-Palmitoyltransferase - therapeutic use</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetes. 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Target tissue resistance</topic><topic>free fatty acids</topic><topic>General aspects</topic><topic>Male</topic><topic>malondialdehyde</topic><topic>Medical sciences</topic><topic>oxfenicine</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>streptozotocin-diabetic rats</topic><topic>Vitamin B Complex - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Kuo-Chu</creatorcontrib><creatorcontrib>Tseng, Chuen-Den</creatorcontrib><creatorcontrib>Lu, Shao-Chun</creatorcontrib><creatorcontrib>Liang, Jin-Tung</creatorcontrib><creatorcontrib>Wu, Ming-Shiou</creatorcontrib><creatorcontrib>Tsai, Ming-Shian</creatorcontrib><creatorcontrib>Hsu, Kwan-Lih</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Kuo-Chu</au><au>Tseng, Chuen-Den</au><au>Lu, Shao-Chun</au><au>Liang, Jin-Tung</au><au>Wu, Ming-Shiou</au><au>Tsai, Ming-Shian</au><au>Hsu, Kwan-Lih</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats</atitle><jtitle>European journal of clinical investigation</jtitle><addtitle>Eur J Clin Invest</addtitle><date>2010-11</date><risdate>2010</risdate><volume>40</volume><issue>11</issue><spage>1002</spage><epage>1010</epage><pages>1002-1010</pages><issn>0014-2972</issn><eissn>1365-2362</eissn><abstract>Eur J Clin Invest 2010; 40 (11): 1002–1010 Background  We compared the haemodynamic and metabolic effects of acetyl‐L‐carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase‐1 inhibitor) in streptozotocin‐induced diabetes in male Wistar rats. Materials and methods  Diabetes was induced by a single tail vein injection of 55 mg kg−1 streptozotocin. The diabetic animals daily treated with either acetyl‐L‐carnitine (150 mg kg−1 in drinking water) or oxfenicine (150 mg kg−1 by oral gavage) for 8 weeks,were compared with the untreated age‐matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. Results  Oxfenicine, but not acetyl‐L‐carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl‐L‐carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl‐L‐carnitine may attenuate the diabetes‐induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA/TBARS content in plasma and aortic walls in diabetes. Acetyl‐L‐carnitine therapy also prevented the diabetes‐related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Conclusion  Acetyl‐L‐carnitine, but not oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly through its decrease of lipid oxidation‐derived MDA/TBARS in the rats with insulin deficiency.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20678118</pmid><doi>10.1111/j.1365-2362.2010.02358.x</doi><tpages>9</tpages></addata></record>
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subjects Acetyl-L-carnitine
Acetylcarnitine - therapeutic use
Analysis of Variance
Animals
Aorta - drug effects
aortic input impedance
Biological and medical sciences
Carnitine O-Palmitoyltransferase - antagonists & inhibitors
Carnitine O-Palmitoyltransferase - therapeutic use
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - physiopathology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Enzyme Inhibitors - therapeutic use
Etiopathogenesis. Screening. Investigations. Target tissue resistance
free fatty acids
General aspects
Male
malondialdehyde
Medical sciences
oxfenicine
Rats
Rats, Wistar
streptozotocin-diabetic rats
Vitamin B Complex - therapeutic use
title Effects of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats
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