Metabolic interactions of AGE inhibitor pyridoxamine and antioxidant alpha-lipoic acid following 22 weeks of treatment in obese Zucker rats.
Life Sci
; 84(15-16): 563-8, 2009 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-19302804
ABSTRACT
AIMS:
The advanced glycation end product inhibitor pyridoxamine (PYR) and the antioxidant alpha-lipoic acid (LA) interact to ameliorate insulin resistance in obese Zucker rats following short-term (6-week) treatment. This study was designed to ascertain whether these unique interactive effects of PYR and LA remain manifest following longer-term (22-week) treatment. MAINMETHODS:
Female obese Zucker rats received vehicle (OV), PYR (OP, 60 mg/kg body wt), racemic LA (rac-LA; OM, 92 mg/kg), the R-(+)-enantiomer of LA (R-LA; OR, 92 mg/kg), or combined treatments with PYR and rac-LA (OPM) or PYR and R-LA (OPR), daily for 22 weeks. KEYFINDINGS:
Individual and combined treatments with PYR, rac-LA, and R-LA significantly (p<0.05) inhibited skeletal muscle protein carbonyls (28-36%), a marker of oxidative damage, and triglyceride levels (21-51%). Plasma free fatty acids were reduced in OM (9%), OR (11%), and OPM (16%), with the greatest decrease (26%) elicited in OPR. HOMA-IR, an index of fasting insulin resistance, was decreased in OP (14%) and OPM (17%) groups, with the greatest inhibition (22%) in OPR. Insulin resistance (glucose-insulin index) was lowered (20%) only in OPR. Insulin-mediated glucose transport in isolated skeletal muscle was improved in OM (34%), OR (33%), OPM (48%) and OPR (31%) groups.SIGNIFICANCE:
Important interactions between PYR and LA for improvements in glucose and lipid metabolism in the female obese Zucker rat are manifest following a 22-week treatment regimen, providing further evidence for targeting oxidative stress as a strategy for reducing insulin resistance.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Piridoxamina
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Ácido Tióctico
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Produtos Finais de Glicação Avançada
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Antioxidantes
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Obesidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article