Dose-dependent effects of acetaminophen and ibuprofen on mitochondrial respiration of human platelets.

Acetaminophen and ibuprofen are widely used over-the-counter medications to reduce fever, pain, and inflammation. Although both drugs are safe in therapeutic concentrations, self-medication is practiced by millions of aged patients with comorbidities that decrease drug metabolism and/or excretion, thus raising the risk of overdosage. Mitochondrial dysfunction has emerged as an important pathomechanism underlying the organ toxicity of both drugs. Assessment of mitochondrial oxygen consumption in peripheral blood cells is a novel research field Cu several applications, including characterization of drug toxicity. The present study, conducted in human platelets isolated from blood donor-derived buffy coat, was aimed at assessing the acute, concentration-dependent effects of each drug on mitochondrial respiration. Using the high-resolution respirometry technique, a concentration-dependent decrease of oxygen consumption in both intact and permeabilized platelets was found for either drug, mainly by inhibiting complex I-supported active respiration. Moreover, ibuprofen significantly decreased the maximal capacity of the electron transport system already from the lowest concentration. In conclusion, platelets from healthy donors represents a population of cells easily available, which can be routinely used in studies assessing mitochondrial drug toxicity. Whether these results can be recapitulated in patients treated with these medications is worth further investigation as potential peripheral biomarker of drug overdose.

Impairment of Mitochondrial Respiration in Metabolic Diseases: An Overview.

Mitochondrial dysfunction has emerged as a central pathomechanism in the setting of obesity and diabetes mellitus, linking these intertwined pathologies that share insulin resistance as a common denominator. High-resolution respirometry (HRR) is a state-of-the-art research method currently used to study mitochondrial respiration and its impairment in health and disease. Tissue samples, cells or isolated mitochondria are exposed to various substrate-uncoupler-inhibitor-titration protocols, which allows the measurement and calculation of several parameters of mitochondrial respiration. In this review, we discuss the alterations of mitochondrial bioenergetics in the main dysfunctional organs that contribute to the development of the obese and diabetic phenotypes in both animal models and human subjects. Herein we review data regarding the impairment of oxidative phosphorylation as integrated mitochondrial function assessed by means of HRR. We acknowledge the critical role of this method in determining the alterations in oxidative phosphorylation occurring in the early stages of metabolic pathologies. We conclude that there is a mutual two-way relationship between mitochondrial dysfunction and insulin insensitivity that characterizes these diseases.

The Mental Status in Patients with Diabetes Mellitus Admitted to a Diabetes Clinic After Presenting in the Emergency Room: The Application of the SCL-90 Scale.

BACKGROUND: Diabetes mellitus (DM) is one of the most serious public health problems, involving increasing costs worldwide. The mental state of a person with DM is varied and ever-changing, such as stress, the pressure to always do everything by the book, sadness, anger, and even denial of the disease, all these are feelings patients with DM will experience throughout their life. AIM: The aim of our study was to assess the presence of mental and psychiatric disorders (anxiety, depressive states, paranoid ideation, phobia, obsessive-compulsive disorder) in a group of patients with DM after hospitalization in the Clinic for Diabetes, Nutrition, and Metabolic Diseases, for various exacerbations of the underlying condition, looking for possible correlations with other cardiovascular risk factors. PATIENTS AND METHODS: Clinical and biological parameters, the presence of acute and chronic complications of the diabetic patients have been evaluated. To assess mental health, the symptom checklist (SCL)-90 questionnaire was conducted for all admitted patients. RESULTS: We observed that the number of patients with obsessive-compulsive disorders was relatively high (23.3%), while depression was present in 17.1% of the patients. Also, 10.6% of patients had hostility and 15.6% had delusional ideation. The presence of psychiatric disorders was associated with a higher age (62 vs. 46.5 years; p <0.001), a longer diabetes duration (11 vs. 9 years; p <0.001), higher fasting glycemia (188 vs. 132 mg/dL; p <0.001) and postprandial glycemia (212 vs. 152 mg/dL; p <0.001), and triglycerides (125 vs. 110 mg/dL; p <0.001). Patients with altered mental status have shown statistically significantly more altered clinical and biological parameters compared to those without these mental disorders. CONCLUSION: Patients with DM represent a psychologically vulnerable population, which is why they should undergo early and regular screening for both psychological and psychiatric conditions, especially at admission.

Improvement of Platelet Respiration by Cell-Permeable Succinate in Diabetic Patients Treated with Statins.

Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first-line lipid-lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM- and statin-induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell-permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.