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Pharmacological And Toxicological Evaluation Of A Synthetic Analog Of L-Carnitine On In Vitro Models

FASEB JOURNAL(2010)

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摘要
The aim of this study was to evaluate the pharmacological and toxicological effects of a synthetic analog of L‐carnitine on in vitro models. For the study we used hepatic and a renal cell lines. For pharmacological evaluation were induced an in vitro model of insulin resistance. Cells were incubated in serum‐free DMEM containing either normal concentrations of glucose (5.5 mM D‐glucose) or high concentrations of glucose (30 mM D‐glucose) for 24 h. Cells were treated with L‐carnitine (2mM) and the analog (0.01, 0.1, 1, 10, and 100 uM, and 1and 2mM) and incubated for 24 h. Glucose and glycogen were determined in medium and cell extracts. For the toxicological evaluation were evaluated the viability and cell proliferation in hepatic and renal cells by using a MTT assay. The results showed that the analog reduced the glucose levels in conditioned media between 20–25% at concentrations of 100 uM, 1 and 2 mM, as compared with control group (p< 0.05). No changes were observed in intracellular glucose levels. However, an increase in the intracellular glycogen levels (100%) was observed. The analogue did no produce changes on cell viability or in cell proliferation in hepatic and renal cells. In conclusion, the synthetic analog is able to reduce the extracellular glucose and increase the intracellular glycogen levels. So, these results indicate that the analog might be used as l‐carnitine for treating the metabolic syndrome.
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关键词
l‐carnitine,toxicological evaluation,synthetic analog
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