The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

BACKGROUND/AIMS: Coenzyme Q(10) (CoQ(10)) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ(10)-based micelle formulation (CoQ(10)-W) and tested it in an exper...

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Detalles Bibliográficos
Autores principales: Quan, Yi, Luo, Kang, Cui, Sheng, Lim, Sun Woo, Shin, Yoo Jin, Ko, Eun Jeong, Kim, Ju Hwan, Chung, Sang J., Bae, Soo Kyung, Chung, Byung Ha, Yang, Chul Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Association of Internal Medicine 2020
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652663/
https://www.ncbi.nlm.nih.gov/pubmed/32279476
http://dx.doi.org/10.3904/kjim.2019.269
Descripción
Sumario:BACKGROUND/AIMS: Coenzyme Q(10) (CoQ(10)) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ(10)-based micelle formulation (CoQ(10)-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). METHODS: We developed CoQ(10)-W from a glycyrrhizic-carnitine mixed layer CoQ(10) micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ(10) (CoQ(10)-L) or CoQ(10)-W for 4 weeks. Their plasma and pancreatic CoQ(10) concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ(10)-W and CoQ(10)-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. RESULTS: The plasma CoQ(10) level was significantly increased in the CoQ(10)-W group compared to that in the CoQ(10)-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ(10)-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ(10)-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ(10)-W but not by CoQ(10)-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ(10)-W than CoQ(10)-L. Electron microscopy revealed that CoQ(10)-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ(10)-L. In vitro studies showed that CoQ(10)-L and CoQ(10)-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. CONCLUSIONS: CoQ(10)-W has better therapeutic efficacy than CoQ(10)-L in TAC-induced DM.

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