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

Abstract

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 signif icantly 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 CoQ10-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.

Effect of Short-Term Tacrolimus Exposure on Rat Liver: An Insight into Serum Antioxidant Status, Liver Lipid Peroxidation, and Inflammation

“…Oxidative hepatic damage and change in liver architecture with significant decrease in GSH concentration, inhibition of SOD and CAT activity, and increased MDA level have been previously reported in a liver toxicity model of rats [ 31 , 32 ], and a link between change in antioxidant status and liver histopathology owing to liver injury has been described [ 33 ]. Additionally, decreased activity of SOD and CAT, reduced GSH concentration, and increased MDA level have been suggested to be responsible for oxidative damage and apoptosis in TAC-induced diabetes mellitus in an animal model [ 34 ]. MDA reflects lipid peroxidation and plays a vital role on oxidative damage.…”

Water-soluble coenzyme Q₁₀ provides better protection than lipid-soluble coenzyme Q₁₀ in a rat model of chronic tacrolimus nephropathy

“…We previously reported the efficacy of CoQ 10 -W in Tac-induced diabetes mellitus [23], and this study ex-tended the evaluation of this effect to Tac-induced renal injury. The results of our study clearly demonstrate that CoQ 10 -W significantly improved renal function and histopathological parameters compared to that with CoQ 10 -L in a rat model of Tac-induced renal injury.…”

Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction

“…For this reason, we developed water-soluble CoQ10 (CoQ10-W) to improve its bioavailability [98]. We found that CoQ10-W may provide more benefits than conventional CoQ10 by diminishing injury in the pancreas [99] and UUO-induced kidney [24]. Table 2 summarizes the management of UUO-induced renal fibrosis using clinical conventional drugs.…”