Tempol modulates the leukocyte response to inflammatory stimuli and attenuates endotoxin-induced sickness behaviour in mice.

Background and aims: Lipopolysaccharide (LPS), an endotoxin, is a component of the outer membrane of Gram-negative bacteria that is able to activate the peripheral immune system, leading to changes in signalling pathways that act locally and systemically to achieve adaptive responses. Sickness behaviour is a motivational state in response to endotoxin exposure and includes depressed activity and a reduction of exploratory behaviour, potentially reorganising organism priorities to cope with infectious diseases. We hypothesised that 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) modulates the leukocyte response to endotoxins and decreases LPS-induced sickness behaviour in mice.Methods: The effects of Tempol on LPS-induced peritonitis and the respiratory burst of neutrophils primed with LPS and triggered by phorbol 12-myristate-13-acetate (PMA) were evaluated. To evaluate the effects of Tempol on sickness behaviour, the mice were submitted to an open field and forced swim tests.Results: Tempol (50-100 µM/106 cells) decreased the respiratory burst of LPS-primed and PMA-stimulated neutrophils in vitro. In vivo, this nitroxide (30 and 100 mg/kg body weight) inhibited leukocyte migration to the peritoneal cavity after LPS administration in mice. Moreover, Tempol pretreatment (30 and 100 mg/kg body weight) before LPS administration also attenuated sickness behavioural changes.Conclusions: Together, these findings shed light on the mechanisms underlying the anti-inflammatory potential and confirm the therapeutic potential of nitroxides.

Nitroxide 4-hydroxy-2,2',6,6'-tetramethylpiperidine 1-oxyl (Tempol) inhibits the reductase activity of protein disulfide isomerase via covalent binding to the Cys400 residue on CXXC redox motif at the a'active site.

BACKGROUND AND AIM: Oxidative stress arising from inflammatory processes is a serious cause of cell and tissue damage. Tempol is an efficient antioxidant with superoxide dismutase-like activity. The purpose of this paper is to address the inhibition of protein disulfide isomerase (PDI), an essential redox chaperone whose active sites contain the Cys-Gly-His-Cys (CXXC) motif, by the nitroxide Tempol. RESULTS: In the presence of Tempol (5-120 µM), the reductase activity of PDI was reversibly affected both in vitro and in activated mice neutrophils, with an IC50 of 22.9 ± 10.8 µM. Inhibitory activity was confirmed by using both the insulin method and fluorescent formation of eosin-glutathione (E-GSH). The capacity of Tempol to bind the enzyme was determined by EPR and mass spectrometry. EPR Tempol signal decreased in the presence of PDI while remained unaffected when PDI thiols were previously blocked with NEM. When total protein was analyzed, 1 and 4 molecules of Tempol were bound to the protein. However, only one was found to be covalently bound to PDI at the a'active site. More specifically, Cys400 was modified by Tempol. CONCLUSION: We have shown that the nitroxide Tempol acts as an inhibitor of PDI through covalent binding to the Cys400 of the protein structure. Since PDI is coupled with the assembly of the NADPH oxidase complex of phagocytes, these findings reveal a novel action of Tempol that presents potential clinical applications for therapeutic intervention to target PDI knockdown in pathological processes in which this protein is engaged.

Green banana pasta diet prevents oxidative damage in liver and kidney and improves biochemical parameters in type 1 diabetic rats.

OBJECTIVE: In this study, the effects of a green banana pasta diet on the oxidative damage from type 1 diabetes mellitus (DM) were investigated. MATERIALS AND METHODS: Formulations containing 25 (F25), 50 (F50), and 75% (F75) of green banana pasta were prepared and included in a 12-week diet of Wistar rats with alloxan-induced type 1 DM. The effects of these formulations in preventing oxidative damage in kidneys and liver homogenates of rats were evaluated using the TBARS assay (lipid peroxidation in liver) and the DNPH assay (protein oxidation in liver and kidneys). Furthermore, the effects of the formulations on the fasting glycemia, fructosamine levels, renal function (creatinine), liver function (enzymes aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and lipid profile (total cholesterol and fractions) in the serum of rats were evaluated in addition to the evaluation of the centesimal composition and microbiological analysis of the produced green banana pasta. RESULTS: An F75 diet prevented hyperglycemia in diabetic rats (p < 0.05) compared to the diabetic rats fed a standard diet (commercial feed). Notably, the protein oxidation in both the liver and kidneys were prevented in diabetic rats on the F50 or F75 diets compared to the control group, whereas the lipid peroxidation was only prevented in the liver (p < 0.05). Moreover, all formulations prevented an increase in the amount of triglycerides in the serum of the rats. The F25 and F50 diet prevented the increase of cholesterol, and the F75-based diet of ALT and fructosamine (p < 0.05) supported the anti-hyperglycemic effects and the protection against oxidative damage. CONCLUSION: The green banana pasta (F75) diet showed great potential for preventing complications associated with diabetes.

Dry Extract of Passiflora incarnata L. leaves as a Cardiac and Hepatic Oxidative Stress Protector in LDLr-/- Mice Fed High-Fat Diet

ABSTRACT The control of dyslipidemia by using herbal products is an important subject for studies. In this study, we evaluated the effects of dry Passiflora incarnata L. extract over dyslipidemia, left ventricular hypertrophy, and hepatic oxidative stress of LDL receptor knockout mice (LDLr-/-). Forty 4-month old male LDLr-/- mice were distributed into four groups: Group standard diet; Group standard diet and 200 mg/kg of body weight of Passiflora incarnata L. leaf dry extract; Group high-fat diet; Group high-fat diet and 200 mg/kg of body weight of Passiflora incarnata L. leaf dry extract. After 30 days, Passiflora incarnata L. dry extract reduced the effects of the high-fat diet, with a decrease of total cholesterol, triglycerides, and increase of high-density lipoprotein (HDL), as well as a reduction of C-reactive protein, alkaline phosphatase and insulin. There was no effect on glucose, Homa index and enzymes aspartate aminotransferase and alanine aminotransferase. However, the prevention of left ventricular hypertrophy occurred, as well as lipid peroxidation and the production of carbonyl proteins, which are both oxidative stress markers. In conclusion, Passiflora incarnata L. dry extract acts in the prevention of dyslipidemia, consequently, hindering the occurrence of hepatic oxidative stress and the development of left ventricular hypertrophy by the increase of serum HDL, in mice that had the effects of a high-fat diet.

Visão farmacoterapêutica em odontologia, frequência e classes de medicamentos prescritos em uma clínica odontológica de um município do sul de Minas Gerais-MG / Pharmacotherapeutic view in dentistry, frequency and therapeutic classes of prescribed drugs at a dental clinic in a city of southern Minas Gerais state

Este trabalho visou avaliar a frequência e classes de medicamentos mais prescritos em uma clínica odontológica, bem como o conhecimento em farmacologia dos entrevistados. Para isto, foi conduzido um estudo observacional com uma amostragem composta por cirurgiões-dentistas (professores) e alunos da clínica integrada de odontologia de uma Universidade do Sul de Minas Gerais. Os dados foram coletados pela aplicação de um questionário individual. A partir disto, a frequência e classes de medicamentos mais prescritos, bem como o conhecimento em farmacologia dos entrevistados foram avaliadas. Entre as 66 pessoas entrevistadas (9 professores e 57 alunos), a maior porcentagem classificaram suas prescrições como de baixa frequência e optam em sua maioria por prescrições utilizando o nome genérico do medicamento, sendo 96,96% destas prescrições realizados por escrito. Na classe dos antibióticos, o mais utilizado pelos profissionais foram Amoxicilina e Clindamicina, na classe dos analgésicos Dipirona Sódica e Paracetamol, na classe dos antiinflamatorios a Nimesulida, os ansiolíticos igualmente distribuídos entre Diazepan, Lorazepan e Midazolan, na classe dos antissépticos a Clorexidina e como protetor gástrico a Ranitidina. Um pequeno percentual (1,52%) dos entrevistados consideraram seu conhecimento farmacológico insuficiente para a prática clínica, 21,21% regular, 63,64% suficiente e 13,63% ótimo. Estes dados indicam que são necessárias novas abordagens para melhorar o conhecimento em farmacologia de dentistas e futuros dentistas, com intuito de promover o uso racional de medicamentos.

In this work was evaluated the frequency and therapeutic classes of prescribed drugs at a dental clinic as well as knowledge in pharmacology of the interviewed. An observational study was conducted from a sample composed by dentists (professors) and undergraduate dental students from a dental clinic of a University of Southern Minas Gerais. The data were collected by applying an individual questionnaire, accordingly, frequency and therapeutic classes of commonly prescribed drugs as well as the knowledge in pharmacology of the interviewed were assessed. Among the 66 people interviewed (9 professors and 57 students), the highest percentage of them rated their prescriptions as low frequency and opted mostly for prescriptions using generic drug names, being writing prescriptions in 96.96% of the cases. In the class of antibiotics, the most used by professionals were Amoxicillin and Clindamycin, in the class of painkillers Sodium Dipyrone and Paracetamol, in the class of anti-inflammatory Nimesulide, anxiolytics class was equally distributed between Diazepam, Lorazepam, and Midazolam, in the class of antiseptics the Chlorhexidine, and how a gastric protector Ranitidine was most prescribed. 1.52% of the interviewed considered their pharmacological knowledge as poor, 21.21% fair, 63.64% good, and 13.63% excellent. These data indicate that new approaches are needed to improve the knowledge in pharmacology of dentists and future dentists, aiming to encourage the rational use of drugs.

Green banana pasta diet prevents oxidative damage in liver and kidney and improves biochemical parameters in type 1 diabetic rats

ABSTRACT Objective In this study, the effects of a green banana pasta diet on the oxidative damage from type 1 diabetes mellitus (DM) were investigated. Materials and methods Formulations containing 25 (F25), 50 (F50), and 75% (F75) of green banana pasta were prepared and included in a 12-week diet of Wistar rats with alloxan-induced type 1 DM. The effects of these formulations in preventing oxidative damage in kidneys and liver homogenates of rats were evaluated using the TBARS assay (lipid peroxidation in liver) and the DNPH assay (protein oxidation in liver and kidneys). Furthermore, the effects of the formulations on the fasting glycemia, fructosamine levels, renal function (creatinine), liver function (enzymes aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and lipid profile (total cholesterol and fractions) in the serum of rats were evaluated in addition to the evaluation of the centesimal composition and microbiological analysis of the produced green banana pasta. Results An F75 diet prevented hyperglycemia in diabetic rats (p < 0.05) compared to the diabetic rats fed a standard diet (commercial feed). Notably, the protein oxidation in both the liver and kidneys were prevented in diabetic rats on the F50 or F75 diets compared to the control group, whereas the lipid peroxidation was only prevented in the liver (p < 0.05). Moreover, all formulations prevented an increase in the amount of triglycerides in the serum of the rats. The F25 and F50 diet prevented the increase of cholesterol, and the F75-based diet of ALT and fructosamine (p < 0.05) supported the anti-hyperglycemic effects and the protection against oxidative damage. Conclusion The green banana pasta (F75) diet showed great potential for preventing complications associated with diabetes.