“…Also, this finding is consistent with a previous observation that acute alcohol treatment induced apoptosis in primary hepatocytes accompanied by ROS production and mitochondrial depolarization [25,26]. In the current study, pretreatment with phyllanthin impeded the decrease of MMP in the HepG2 cells and the co-cultured cells.…”
“…Also, this finding is consistent with a previous observation that acute alcohol treatment induced apoptosis in primary hepatocytes accompanied by ROS production and mitochondrial depolarization [25,26]. In the current study, pretreatment with phyllanthin impeded the decrease of MMP in the HepG2 cells and the co-cultured cells.…”
“…On the other hand, Co-Q 10 pretreatment inhibited mitochondrial damage, expression of cytochrome c and cell apoptosis( 44 ). The same inhibitory effect was observed with LC administration( 45 ).…”
Statins are widely used in patients with hyperlipidemia and whom with high risk of cardiovascular diseases. Unfortunately, statins also exert some adverse effects on the liver and pancreas and enhance the risk of type 2 diabetes mellitus. The objective of the present research was to investigate the protective effects of coenzyme Q10 (Co-Q10) and L-carnitine (LC) on statins induced toxicity on pancreatic mitochondria in vivo. Seven groups of male Wistar rats received atorvastatin (20 mg/kg, p.o.), atorvastatin + Co-Q10 (10 mg/kg, i.p.), atorvastatin + LC (500 mg/kg, i.p.), lovastatin (80 mg/kg, p.o), lovastatin + Co-Q10 (10 mg/kg, i.p.), and lovastatin + LC (500 mg/kg, i.p.). Serum glucose and insulin levels were measured before and after two weeks of treatment, while the pancreas was removed and toxic effects of statins, as well as the protective effects of Co-Q10 and LC were assessed. The results showed that atorvastatin and lovastatin significantly increased glucose level and decreased insulin secretion. The glucose level in Co-Q10 and LC groups was significantly lower than statins alone groups. The findings also showed that statin groups had higher rate of pancreatic toxicity including higher level of reactive oxygen species production, decreased cytochrome c oxidase activity, collapse of mitochondrial membrane potential and swelling in comparison to controls. These factors were significantly diminished by co-administration of Co-Q10 or LC compared to statin groups alone. Additionally, supplements caused a significant increase in serum insulin and succinate dehydrogenase activity. Our study provided new evidence supporting beneficial effects of Co-Q10 and LC on statin-induced pancreatic toxicity.
“…In addition, CoQ10 involves NAD(P)H-oxidoreductase-dependent reactions such as in NO synthesis in Golgi and plasma membranes [ 25 ]. Previous studies have indicated that CoQ10 attenuates cellular apoptosis in corneal fibroblasts by inhibition of mitochondrial depolarization [ 13 , 26 ] and prevents HUVEC apoptosis through suppression of mitochondria dependent caspase 3 protein. However, there has been no report investigating the direct effect of CoQ10 on EPC in vitro.…”
Section: Discussionmentioning
confidence: 99%
“…After 15 min, the cells were washed with PBS twice. Apoptosis was detected by a change in JC-1-labeled fluorescence from red to green with flow cytometer and analyzed with Cell Quest Alias software, as described in the literature [ 13 ].…”
Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.
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