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Objectives: To evaluate the effects of coenzyme Q10 (CoQ10) on alveolar bone remodeling and orthodontic tooth movement (OTM). Materials and methods: An orthodontic appliance was placed in 42 female Sprague‒Dawley rats were divided into two groups: the orthodontic force (OF) group (n = 21) and the OF + CoQ10 (CoQ10) treatment group (n = 21). Each group was divided into 3 subgroups, and the rats were sacrificed on days 3, 7 and 14. The rats in CoQ10 and OF groups were administered 100 mg/kg b.w./day CoQ10 (in 1 mL/b.w. soybean oil) and 1 mL b.w./day soybean oil, respectively, by orogastric gavage. The OTM was measured at the end of the experiment. The osteoclast, osteoblast and capillary numbers; vascular endothelial growth factor (VEGF), receptor activator nuclear kappa B ligand (RANKL) and osteoprotegrin (OPG) levels in tissue; and total antioxidant status (TAS) and total oxidant status (TOS) in blood were determined. Results: Compared with the OF group, the CoQ10 treatment group exhibited decreased orthodontic tooth movement and osteoclast and capillary numbers. Indeed, the levels of VEGF and RANKL decreased, while the levels of OPG increased except on day 7. Additionally, the CoQ10 treatment group exhibited lower TOS and higher TAS on days 7 and 14 (p < 0.05). Histological findings showed that the morphology of osteoblasts changed in the CoQ10 group; however, there was no significant difference in the number of osteoblasts between the groups (p > 0.05). Conclusion: Due to its effect on oxidative stress and inflammation, CoQ10 regulates bone remodeling by inhibiting osteoclast differentiation, promoting osteoblast differentiation and reducing the amount of OTM. Clinical relevance: Considering that OTM may be slowed with the use of CoQ10, topics such as orthodontic treatment duration, orthodontic force activation and appointment frequency should be considered in treatment planning. It is predicted that the use of CoQ10 will support the effectiveness of treatment in clinical applications such as preventing relapse in orthodontic treatment by regulating bone modulation and anchorage methods that suppress/optimize unwanted tooth movement. [ABSTRACT FROM AUTHOR]

Purpose: Methimazole is an anti-thyroid agent, especially as main therapy option for Graves' disease in children and adults. Drug induced pancreatitis is one of the known adverse effect of methimazole mentioned in case reports. However, the detailed molecular mechanisms of methimazole-induced pancreatitis are still unclear. In this study, the aim is to investigate the adverse effect of methimazole on pancreas cell stress mechanism and apoptosis. Methods: Cytotoxicity was evaluated in human pancreas/duct (PANC-1) cell line. Total oxidant (TOS) and antioxidant status (TAS) for oxidative stress index, glutathione (GSH) level and endoplasmic reticulum (ER) stress biomarkers were evaluated by ELISA. Reactive oxygen species (ROS) levels and apoptosis were evaluated by flow-cytometer. Results: The 30% inhibition rate concentration (IC30) value was determined as 53 mM in PANC-1 cells. The exposure concentrations were in the range of 0-40 mM for 48 hours. Methimazole might induce cellular stress conditions. ROS production increases depending on concentration, and this increase shows parallelism with the increase in ER stress biomarkers such as TOS, ERN1 and CASPASE12. Conversely, there was no significant difference between control and exposure groups in terms of apoptosis. Conclusion: In conclusion, methimazole might have triggered the mechanisms of inflammation or autophagy in the pancreatic cells. However, there is still a need for in vitro and in vivo studies including other cellular parameters related to apoptosis. [ABSTRACT FROM AUTHOR]

UR-144, a cannabinoid receptor agonist, is widely used alone or in combination with other synthetic cannabinoids (SCs) all over the world. At overdose, cardiovascular symptoms have been reported and the underlying molecular mechanisms of these adverse effects are not known. It is highly important to clarify the toxic effects of UR-144 for the treatment of poisoning. In the present study, the molecular mechanism of cytotoxic effects of UR-144 is evaluated on a cardiomyoblastic cell line using WST-1 and LDH assays. Apoptosis/necrosis, autophagy, and ROS (reactive oxygen species) levels were determined using flow cytometry. Cytoplasmic Ca2+ levels were measured by using a fluorogenic calcium-binding dye. Released and cytoplasmic troponin T levels, a specific marker of cardiotoxicity, were examined with western blot. For the evaluation of the role of DAPK1, on UR-144-induced cell death, DAPK1 activity and DAPK1 protein level were investigated. Its cytotoxic effects increased in a dose-dependent manner for WST-1 and LDH assays, while membrane damage, one of the signs of necrotic cell death, was more remarkable than damage to mitochondria. Cytoplasmic Ca2+ levels rose after high-dose UR-144 treatment and inhibition of DAPK1 activity ameliorated UR-144-induced cytotoxicity. Released troponin T significantly increased at a dose of 200 µM. ROS and total antioxidant capacity of cells were both reduced following high dose UR-144 treatment. The results indicated that UR-144-induced autophagic and necrotic cell death might be a consequence of elevated cytoplasmic Ca2+ levels and DAPK1 activation. However, in vivo/clinical studies are needed to identify molecular mechanisms of cardiotoxic effects of UR-144. [ABSTRACT FROM AUTHOR]

Background/aim: Dapagliflozin (DAPA), sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an insulin-independent antidiabetic drug used to control hyperglycaemia by promoting glucose excretion from the kidney. Its adverse effects include orthostatic hypotension, dehydration and urinary tract and genital infections caused by glycosuria. DAPA is subjected to constant additional monitoring, as drug-related adverse reactions are frequently updated in line with the results of case studies, clinical trials and in vivo studies. Some antidiabetic drugs have shown potential harmful effects on the male reproductive system; however, the effects of DAPA have not been sufficiently studied in this capacity. Aiming to fill this gap in the literature, the present work investigates the toxic effects of DAPA on the male reproductive system. Materials and methods: Diabetes was induced using streptozotocin (STZ) in adult male Sprague-Dawley (SD) rats. DAPA (10 mg/kg) was administered by gavage to the diabetic rats over 28 days, after which the animals were sacrificed. The biochemical, morphological and histological examinations were performed on testicle, sperm and plasma samples. Results: As a result of this study, we observed reproductive system damage in the form of induction of apoptosis in the seminiferous tubules, changes in testis and sperm parameters and oxidative damage, alongside the development of diabetes in test animals. With the exception of sperm morphological damage, the changes observed in diabetic animals treated with DAPA were similar to those of the control group. Improvements were observed in histological, hormonal and proliferative parameters in the DAPA group compared to the DC group. Conclusion: Even if DAPA is found to have antioxidant effects, it may raise abnormal sperm counts through a mechanism completely independent of these effects and thus may not have a significant toxic effect on the male reproductive system. [ABSTRACT FROM AUTHOR]