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1.
Naunyn Schmiedebergs Arch Pharmacol ; 396(8): 1837-1845, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37074393

RESUMO

Doxorubicin (DOX), which is used as a chemotherapeutic agent in the treatment of tumors, has limited use due to its toxicity in various organs and tissues. One of the organs where DOX has a toxic effect is the lung. DOX shows this effect by increasing oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a homologue of pantothenic acid, has anti-inflammatory, antioxidant, and anti-apoptotic properties. Therefore, the purpose of our investigation was to explore how DEX could counteract the harmful effects of DOX on the lungs. Thirty-two rats were used in the study, and 4 groups were formed (control, DOX, DOX + DEX, and DEX). In these groups, parameters of inflammation, ER stress, apoptosis, and oxidative stress were evaluated by immunohistochemistry, RT-qPCR, and spectrophotometric methods. In addition, lung tissue was evaluated histopathologically in the groups. While CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions increased in the DOX group, Bcl-2 gene expression levels significantly decreased. In addition, changes in Bax and Bcl-2 were supported immunohistochemically. There was a significant increase in oxidative stress parameters and a significant decrease in antioxidant levels. In addition, an increase in inflammatory marker (TNF-α and IL-10) levels was determined. There was a decrease in CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions and an increase in Bcl-2 gene expression in the DEX-treated group. In addition, it was determined that there was a decrease in oxidative stress levels and inflammatory findings. The curative effect of DEX was supported by histopathological findings. As a result, it was experimentally determined that DEX has a healing effect on oxidative stress, ER stress, inflammation, and apoptosis in lung damage caused by DOX toxicity.


Assuntos
Ácido Pantotênico , Animais , Ratos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Estresse do Retículo Endoplasmático/fisiologia , Doxorrubicina/efeitos adversos , Ácido Pantotênico/uso terapêutico , Antioxidantes/uso terapêutico , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
2.
Dermatol Ther ; 35(9): e15695, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35791704

RESUMO

Combination therapy with biotin and dexpanthenol is a well-known practice in preventing and treating hair loss, however, it is not well studied. In this study, we compared the efficacy of the 6-week treatment with two brands of biotin and dexpanthenol for the treatment of diffuse hair loss. Fifty eligible patients with diffused pattern hair loss, (41 women and 9 men) were randomized in a 1:1 ratio to receive either 6 weekly injections of dexpanthenol ampoule 250 mg/2 ml and biotin ampoule 5 mg/1 ml, manufactured by Pars Behvarzan or Bayer Company. Combing test, Standard scalp photography and trichoscan assessment were performed before the first treatment session and one and 8 weeks after the last one. Patients' satisfaction and drug adverse reactions were also recorded. One and eight weeks after the last treatment session, hair fall count and total hair density significantly improved in both groups (p-value <0.01 for hair fall count and 0.04 and 0.02, for hair density in Pars and Bayer groups, respectively). There was no significant difference between the two groups in any other trichoscan parameter, except for improvement in terminal/vellus hair ratio in the Bayer group in both follow up visits, compared to the Pars group (p-value = 0.02 and 0.033 for weeks one and eight). Six-week treatment with both brands of biotin and dexpanthenol was effective and safe in people with diffused pattern hair loss.


Assuntos
Alopecia , Biotina , Ácido Pantotênico , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Biotina/uso terapêutico , Método Duplo-Cego , Feminino , Cabelo , Humanos , Injeções Intramusculares , Masculino , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/uso terapêutico , Resultado do Tratamento
3.
Biomed Pharmacother ; 141: 111823, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147902

RESUMO

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.


Assuntos
Ácido Ascórbico , Sulfato de Magnésio , Niacinamida , Ácido Pantotênico , Piridoxina , Riboflavina , Sepse , Tiamina , Animais , Feminino , Masculino , Ratos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Composição de Medicamentos , Lipopolissacarídeos/toxicidade , Sulfato de Magnésio/química , Sulfato de Magnésio/farmacologia , Sulfato de Magnésio/uso terapêutico , Camundongos Endogâmicos BALB C , Niacinamida/química , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ácido Pantotênico/química , Ácido Pantotênico/farmacologia , Ácido Pantotênico/uso terapêutico , Piridoxina/química , Piridoxina/farmacologia , Piridoxina/uso terapêutico , Ratos Sprague-Dawley , Ratos Wistar , Riboflavina/química , Riboflavina/farmacologia , Riboflavina/uso terapêutico , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/patologia , Superóxido Dismutase/metabolismo , Tiamina/química , Tiamina/farmacologia , Tiamina/uso terapêutico
4.
Exp Dermatol ; 30(5): 745-750, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403711

RESUMO

This study aimed to investigate the molecular effects of radiation and subsequent aftercare treatment with dexpanthenol-containing ointment and liquid on established full-thickness 3D skin models depicting acute radiodermatitis and mucositis. To mimic radiomucositis and radiodermatitis, non-keratinized mucous membrane and normal human skin models were irradiated with 5 Gray. Afterwards, models were treated topically every second day with dexpanthenol-containing ointment or liquid in comparison with placebo and untreated controls. On day 7 after irradiation, histological examination showed impairments in irradiated models. In contrast, models treated with dexpanthenol-containing ointment or liquid showed a completely restored epidermal part. While gene expression profiling revealed an induction of genes related to a pro-inflammatory milieu, oxidative stress and an impaired epidermal differentiation after irradiation of the models, aftercare treatment with dexpanthenol-containing ointment or liquid revealed anti-oxidative and anti-inflammatory effects and had a positive effect on epidermal differentiation and structures important for physical and antimicrobial barrier function. Our findings confirm the potential of our established models as in vitro tools for the replacement of pharmacological in vivo studies regarding radiation-induced skin injuries and give indications of the positive effects of dexpanthenol-containing externals after radiation treatments as part of supportive tumor treatment.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Queratinócitos/efeitos dos fármacos , Mucosa Bucal/efeitos da radiação , Pomadas/uso terapêutico , Ácido Pantotênico/análogos & derivados , Administração Tópica , Assistência ao Convalescente , Epiderme/efeitos dos fármacos , Humanos , Ácido Pantotênico/uso terapêutico , Cicatrização/efeitos dos fármacos
5.
Int Urol Nephrol ; 51(8): 1387-1394, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190296

RESUMO

PURPOSE: Contrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN. METHODS: Twenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp + CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500 mg/kg for 5 days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp + CIN groups, L-NAME (10 mg/kg), tenoxicam (0.5 mg/kg) and sodium amidotrizoate (10 ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected. RESULTS: When the Dexp + CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels. CONCLUSIONS: Dexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.


Assuntos
Antioxidantes/uso terapêutico , Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Ácido Pantotênico/análogos & derivados , Animais , Masculino , Ácido Pantotênico/uso terapêutico , Distribuição Aleatória , Ratos Sprague-Dawley
6.
Mol Neurobiol ; 56(5): 3638-3656, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30173408

RESUMO

Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. The most prevalent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN) associated with mutations in the gene of pantothenate kinase 2 (PANK2), which is essential for coenzyme A (CoA) synthesis. There is no cure for NBIA nor is there a standard course of treatment. In the current work, we describe that fibroblasts derived from patients harbouring PANK2 mutations can reproduce many of the cellular pathological alterations found in the disease, such as intracellular iron and lipofuscin accumulation, increased oxidative stress, and mitochondrial dysfunction. Furthermore, mutant fibroblasts showed a characteristic senescent morphology. Treatment with pantothenate, the PANK2 enzyme substrate, was able to correct all pathological alterations in responder mutant fibroblasts with residual PANK2 enzyme expression. However, pantothenate had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of pantothenate in particular mutations was also confirmed in induced neurons obtained by direct reprograming of mutant fibroblasts. Our results suggest that pantothenate treatment can stabilize the expression levels of PANK2 in selected mutations. These results encourage us to propose our screening model as a quick and easy way to detect pantothenate-responder patients with PANK2 mutations. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of pantothenate.


Assuntos
Ferro/metabolismo , Mutação/genética , Neurodegeneração Associada a Pantotenato-Quinase/tratamento farmacológico , Neurodegeneração Associada a Pantotenato-Quinase/genética , Ácido Pantotênico/uso terapêutico , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Coenzima A/metabolismo , Metabolismo Energético/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipofuscina/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Neurodegeneração Associada a Pantotenato-Quinase/patologia , Ácido Pantotênico/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Carbonilação Proteica/efeitos dos fármacos
7.
Balkan Med J ; 36(2): 88-95, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30322831

RESUMO

Background: Postoperative complications occur after periodontal plastic surgeries, but an ideal treatment to overcome them has not been found yet. Aims: To evaluate the effects of topically applied Oral-norm gel on the healing of excisional wounds. Study Design: Animal experiment. Methods: Excisional wounds with a diameter of 3 mm were made in the center of the palatal mucosa of 63 Sprague Dawley rats. Seven animals were sacrificed at time 0. The remaining rats were divided into two groups: a test group in which the topical Oral-norm gel was applied three times a day and a control group in which nothing was applied. Seven animals in each group were sacrificed at 3, 7, 14, and 21 days. Mean wound surface area was measured photographically, while wound healing and width were evaluated microscopically. Results: The mean wound surface area decreased significantly after 3 days in both groups (p<0.001). Between days 3 and 7, the mean wound surface area decreased from 6.62 (2.85) to 0.83 (1.62) mm2 in the control group and 5.07 (0.88) to 1.42 (1.67) mm2 in the test group. The wound width decreased significantly on day 7 in both groups (p<0.001), with no further changes by day 14. Both groups had a significant increase in inflammation and vascularization on day 3 (p<0.001), with a reduction thereafter. No significant differences in macroscopic and microscopic measurements were observed between the groups at any time point (p>0.05). Conclusion: The Oral-norm gel has no positive healing effects in the palatal mucosa of rats.


Assuntos
Administração Tópica , Combinação de Medicamentos , Palato/efeitos dos fármacos , Cicatrização , Animais , Modelos Animais de Doenças , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Palato/lesões , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/farmacologia , Ácido Pantotênico/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley/lesões , Ácidos Undecilênicos/farmacologia , Ácidos Undecilênicos/uso terapêutico
8.
Transplant Proc ; 50(10): 3135-3143, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577179

RESUMO

OBJECTIVE: We aimed to investigate the protective and therapeutic effects of dexpanthenol (DXP) on liver injuries induced by ischemia-reperfusion (IR) in an in vivo rat model. METHODS: Thirty-two rats were randomly divided into 4 experimental groups (n = 8 in each group: Sham, IR, DXP, and DXP+IR. DXP (500 mg/kg) was intraperitoneally administered for 30 min before 60 min of ischemia, followed by 60 min of reperfusion to rats in the DXP and DXP+IR groups. All rats were euthanized on day 10 to evaluate immunohistopathological changes as well as tissue levels of oxidants and antioxidants. RESULTS: IR decreased total glutathione (tGSH) levels in IR group when compared to the Sham group. DXP supplementation to IR group significantly ameliorated tGSH levels (P < .05). IR also elevated myeloperoxidase production compared to the Sham group, whereas DXP treatment prevented these hazardous effects. However, plasma superoxidedismutase, catalase, and malondialdehyde levels did not differ between the DXP+IR than the IR rats. Histologic tissue damage was reduced in the DXP and DXP+IR group. CONCLUSION: Liver IR is an inevitable problem during liver surgery. Our results suggested that DXP pretreatment suppressed oxidative stress and increased antioxidant levels in a rat model of liver IR.


Assuntos
Fígado/lesões , Ácido Pantotênico/análogos & derivados , Traumatismo por Reperfusão/prevenção & controle , Complexo Vitamínico B/uso terapêutico , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Fígado/patologia , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Ácido Pantotênico/uso terapêutico , Peroxidase , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
9.
Homeopathy ; 107(4): 274-279, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30144788

RESUMO

INTRODUCTION: Analysis of data derived from homeopathic pathogenetic trials (HPTs, homeopathic drug provings) has been a challenge. Most parts of the homeopathic pharmacopeia were sourced from Hahnemann's Materia Medica Pura (1825-1833), TF Allen's Encyclopedia (1874) and Constantine Hering's Materia Medica (1879-1891), well before randomised controlled trials were in use. As a result, such studies and their outcomes harbour a large risk of inclusion of unreliable symptoms. AIMS AND OBJECTIVE: The main purpose of this article is to introduce Quantitative and Qualitative Pathogenetic Indices to improve the method of analysis of symptoms. MATERIALS AND METHODS: The data from HPTs for human immunodeficiency virus nosode, hepatitis C nosode, capsaicin alkaloids (capsaicin and dihydrocapsaicin) and hydroquinone (HQ) were extracted and analysed in terms of novel Qualitative and Quantitative Pathogenetic Indices. Taken into the consideration were the qualitative aspect of a symptom (i.e. its intensity), and the quantitative aspect by calculating the number of symptoms per volunteer per day. The pathogenetic effects and data evaluation indices were calculated for each HPT. A comparison was made of symptoms of verum versus placebo provers in terms of their quantity and quality. RESULTS: Four HPTs involving 81 volunteers (56 on verum and 25 on placebo) generated 555 symptoms or pathogenetic effects (excluding run-in phase symptoms), of which 448 (81%) were reported by volunteers who were in the verum arm, and 107 (19%) were reported by volunteers on placebo. The overall mean incidence of pathogenetic effects for the four HPTs was thus 8 per verum prover and 4.28 per placebo prover. The corresponding mean Quantitative Pathogenetic Index was 0.23 symptoms per volunteer per day for the verum arm and 0.12 symptoms per volunteer per day for the placebo arm. The overall mean incidence of pathogenetic effects in the run-in phase was less. The overall mean Qualitative Pathogenetic Index (number of symptoms, of a given intensity, per volunteer per day) for the verum arm was 0.09 versus 0.05 for the placebo arm. CONCLUSION: The symptoms exhibited by volunteers in the verum arm were more numerous and more intense than those in the placebo arm. An innovative and logical method of reporting of symptoms and analysis has been introduced by the use of these pathogenetic indices, which can be used in future as measurement tools for analysis of data from HPTs.


Assuntos
Índice de Gravidade de Doença , Fatores de Virulência , Cisteína/uso terapêutico , Coleta de Dados/métodos , Método Duplo-Cego , Combinação de Medicamentos , Homeopatia/métodos , Humanos , Ácido Pantotênico/uso terapêutico , Placebos/uso terapêutico , Valores de Referência
10.
J Cell Biochem ; 119(9): 7479-7489, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29775243

RESUMO

The purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)-induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO2 ), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase-3 were determined. BP and SO2 values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO-induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO-induced cardiotoxicity.


Assuntos
Cardiomiopatias/prevenção & controle , Estresse Oxidativo , Ácido Pantotênico/análogos & derivados , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Catalase , Glutationa/análise , Glutationa Peroxidase , Isoproterenol/toxicidade , Masculino , Malondialdeído/análise , Ácido Pantotênico/farmacologia , Ácido Pantotênico/uso terapêutico , Ratos , Ratos Wistar , Superóxido Dismutase
11.
Front Immunol ; 9: 365, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29535733

RESUMO

The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5's promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4+ T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4+ and CD8+ T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.


Assuntos
Proliferação de Células/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Mycobacterium tuberculosis/fisiologia , Ácido Pantotênico/uso terapêutico , Tuberculose/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Imunidade Adaptativa , Animais , Células Cultivadas , Modelos Animais de Doenças , Humanos , Imunidade Inata , Inflamação , Pulmão/imunologia , Pulmão/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Tuberculose/imunologia , Tuberculose/microbiologia
12.
PLoS One ; 13(3): e0192028, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29522513

RESUMO

In cells, phosphorylation of pantothenic acid to generate phosphopantothenic acid by the pantothenate kinase enzymes is the first step in coenzyme A synthesis. Pantothenate kinase 2, the isoform localized in neuronal cell mitochondria, is dysfunctional in patients with pantothenate kinase-associated neurodegeneration. Fosmetpantotenate is a phosphopantothenic acid prodrug in clinical development for treatment of pantothenate kinase-associated neurodegeneration, which aims to replenish phosphopantothenic acid in patients. Fosmetpantotenate restored coenzyme A in short-hairpin RNA pantothenate kinase 2 gene-silenced neuroblastoma cells and was permeable in a blood-brain barrier model. The rate of fosmetpantotenate metabolism in blood is species-dependent. Following up to 700 mg/kg orally, blood exposure to fosmetpantotenate was negligible in rat and mouse, but measurable in monkey. Consistent with the difference in whole blood half-life, fosmetpantotenate dosed orally was found in the brains of the monkey (striatal dialysate) but was absent in mice. Following administration of isotopically labeled-fosmetpantotenate to mice, ~40% of liver coenzyme A (after 500 mg/kg orally) and ~50% of brain coenzyme A (after 125 µg intrastriatally) originated from isotopically labeled-fosmetpantotenate. Additionally, 10-day dosing of isotopically labeled-fosmetpantotenate, 12.5 µg, intracerebroventricularly in mice led to ~30% of brain coenzyme A containing the stable isotopic labels. This work supports the hypothesis that fosmetpantotenate acts to replace reduced phosphopantothenic acid in pantothenate kinase 2-deficient tissues.


Assuntos
Coenzima A/metabolismo , Modelos Animais de Doenças , Neurodegeneração Associada a Pantotenato-Quinase/tratamento farmacológico , Ácido Pantotênico/análogos & derivados , Pró-Fármacos/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Linhagem Celular Tumoral , Humanos , Macaca fascicularis , Masculino , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurodegeneração Associada a Pantotenato-Quinase/metabolismo , Ácido Pantotênico/farmacocinética , Ácido Pantotênico/farmacologia , Ácido Pantotênico/uso terapêutico , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Interferência de RNA , Ratos Sprague-Dawley , Especificidade da Espécie
13.
J Craniofac Surg ; 28(8): 2139-2142, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28938325

RESUMO

OBJECTIVE: To investigate the effect of dexpanthenol-vitamin A (Nazalnem) ointment applied to the surface of silastic splints with an airway immediately after nasal septal surgery on postoperative complaints and nasal mucosa function. MATERIALS AND METHODS: The study enrolled 60 patients undergoing nasal septoplasty surgery. Group 1 (n = 30) received silastic splints with ointment containing dexpanthenol-vitamin A (Nazalnem), and Group 2 (n = 30), the control group, received silastic splints with vaseline. Of these patients, 2 patients from the Group 1 and 9 from the Group 2 were excluded.A thin layer of ointment was applied to the flat side of a silastic splint with an airway. The splints were removed on the second postoperative day. Patients were evaluated preoperatively and 1 and 2 weeks postoperatively using a visual analog scale and the Sino-Nasal Outcome test (SNOT-22). Mucociliary clearance (MCC) tests were performed at the same times. RESULTS: Visual analog scale for nasal crusting, nasal congestion, and foul odor was better in Group 1 than in Group 2 both at 1 week and at 2 weeks postoperatively (P < 0.05).The SNOT scores were significantly lower in Group 1 than in Group 2 at 1 week (P < 0.01), but did not differ at 2 weeks postoperatively (P > 0.05).Postoperatively, the MCC were insignificant between the groups and within the groups at 1 and 2 weeks (P > 0.05). CONCLUSION: Although Dexpanthenol-Vitamin A ointment had no direct effect on wound healing, it had significant effects on crusting, obstruction, and foul smell. However, silastic splints with dexpanthenol did not improve the MCC of the nose.


Assuntos
Dimetilpolisiloxanos/uso terapêutico , Septo Nasal/cirurgia , Ácido Pantotênico/análogos & derivados , Rinoplastia/métodos , Contenções , Vitamina A/uso terapêutico , Humanos , Depuração Mucociliar , Ácido Pantotênico/uso terapêutico , Resultado do Tratamento
14.
Eur J Oncol Nurs ; 29: 1-7, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28720256

RESUMO

PURPOSE: Radiotherapy-induced moist desquamation (RIMD) is a complication that can affect patients' quality of life and jeopardize radiotherapy outcomes. The curative use of a hydroactive colloid gel has previously been shown effective in the management of RIMD in breast cancer patients. This study aimed at investigating the efficacy of this same gel but in the prevention of RIMD. METHODS: A group of breast cancer patients who applied the hydroactive gel from start to end of post-lumpectomy radiotherapy (Preventive Hydrogel group) were compared with two groups of matched historical controls: a group applying a dexpanthenol cream throughout their therapy and a group applying first the dexpanthenol cream then, after 11-14 fractions of radiotherapy, the hydroactive gel (Curative Hydrogel group). All patients received identical fractionation regimen. The clinical outcomes were the incidence and time to onset of RIMD. KEY RESULTS: After 25 fractions of radiotherapy (50 Gy), patients in the Preventive Hydrogel group (N = 202) developed RIMD significantly less frequently and later than patients in the Dexpanthenol group (N = 131; incidence = 7% vs 35% respectively, odds ratios = 7.27; probability of RIMD-free survival after 50 Gy = 0.88 vs 0.62). There were no significant differences between the Preventive and the Curative Hydrogel group (N = 87). CONCLUSIONS: These findings confirm our previous results: applying the hydroactive colloid gel, rather than dexpanthenol, delayed the onset and reduced the incidence of RIMD in breast cancer patients. However, applying the hydrogel preventively offered no statistically significant advantages over applying it curatively.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/radioterapia , Coloides/uso terapêutico , Ácido Pantotênico/análogos & derivados , Radiodermite/tratamento farmacológico , Radiodermite/etiologia , Radioterapia/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Ácido Pantotênico/uso terapêutico , Qualidade de Vida
15.
Reprod Sci ; 24(2): 285-290, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27313118

RESUMO

OBJECTIVE: Dexpanthenol (Dxp), antioxidant and anti-inflammatory agent, plays an important role in the repair systems against oxidative stress and inflammatory response. The objective of this study is to determine the effect of Dxp on experimental endometriosis model. STUDY DESIGN: A prospective experimental study was conducted in Experimental Animal Laboratory of Mustafa Kemal University, Hatay. Twenty nonpregnant female Wistar albino rats, in which experimental model of endometriosis was surgically induced, were randomly divided into 2 groups. Group 1 was administered 500 mg/kg/d Dxp intraperitoneally for 14 days, and group 2 was given the same amount of saline solution. After 2 weeks of medication, the rats were killed and implant volumes, histopathologic scores; and levels of serum total antioxidant status, total oxidant status (TOS), and oxidative stress index (OSI) were evaluated. Plasma and peritoneal fluid levels of tumor necrosis factor α (TNF-α) were analyzed. RESULTS: The endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values were significantly decreased ( P < .05) in the Dxp group compared to the control group. Plasma and peritoneal fluid TNF-α levels were significantly decreased ( P < .05) in the Dxp group compared to the control group. CONCLUSION: Dexpanthenol has free radical scavenger effects, and antioxidant properties has significantly regressed endometriotic implant volumes, histopathologic scores, and serum TOS and OSI values. Serum and peritoneal fluid TNF-α levels were significantly decreased in the Dxp group. So Dxp decreased oxidative stress.


Assuntos
Anti-Inflamatórios/uso terapêutico , Endometriose/metabolismo , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Pantotênico/análogos & derivados , Substâncias Protetoras/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Líquido Ascítico/metabolismo , Modelos Animais de Doenças , Feminino , Ácido Pantotênico/farmacologia , Ácido Pantotênico/uso terapêutico , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
16.
Facial Plast Surg ; 32(2): 225-31, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27097145

RESUMO

Various creams are available for superficial second-degree burns (SSDB) of the face. We evaluated provitamin pantothenic acid versus ß-glucan for SSDB of the face using the O2C laser Doppler system and digital photo analysis. Out of 20 patients (January to December 2012) with facial burns, 7 with SSDB of both cheeks were included to our study. Burned cheek wounds were treated using pantothenic acid or ß-glucan. Digital photos of marked regions were taken daily from predefined distances. Microcirculation was measured at marked regions for 7 days at scheduled time points using the O2C laser Doppler. Data were evaluated using the SPSS program (SPSS Inc., Chicago, IL). Wounds treated with ß-glucan showed faster reepithelialization. O2C laser Doppler measurements showed faster increase in SO2, microvascular perfusion, hemoglobin content, and blood flow. This correlated good with clinical Vancouver Scar Scale results. Although not statistically significant, ß-glucan cream therapy of SSDB results in aesthetically superior outcome and faster reepithelialization.


Assuntos
Queimaduras/tratamento farmacológico , Traumatismos Faciais/tratamento farmacológico , Ácido Pantotênico/uso terapêutico , Complexo Vitamínico B/uso terapêutico , beta-Glucanas/uso terapêutico , Adolescente , Adulto , Idoso , Queimaduras/diagnóstico por imagem , Traumatismos Faciais/diagnóstico por imagem , Humanos , Fluxometria por Laser-Doppler , Pessoa de Meia-Idade , Fotografação , Provitaminas/uso terapêutico , Creme para a Pele/uso terapêutico , Índices de Gravidade do Trauma , Adulto Jovem
17.
J Matern Fetal Neonatal Med ; 29(11): 1801-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26135783

RESUMO

OBJECTIVE: Dexpanthenol (Dxp) plays a major role in cellular defense and in repair systems against oxidative stress and inflammatory response and it has not yet been evaluated in treatment of bronchopulmonary dysplasia (BPD). We tested the hypothesis that proposes whether Dxp decreases the severity of lung injury in an animal model of BPD. METHODS: Forty rat pups were divided into four groups: control, control + Dxp, hyperoxia and hyperoxia + Dxp. All animals were processed for lung histology and tissue analysis. The degree of lung inflammation, oxidative and antioxidant capacity was assessed from lung homogenates. RESULTS: Lung injury score and alveol diameter increased in the hyperoxia group (p < 0.001). Median level of malondialdehyde, total oxidant status and oxidative stress indexes was significantly higher in the hyperoxia group compared to the other groups. The median superoxide dismutase activity in the hyperoxia group was notably less than those of control + Dxp and hyperoxia + Dxp groups (p < 0.01). Similarly, lung catalase, glutathione (GSH) peroxidase and reduced GSH activities in the hyperoxia group were significantly lower than other groups. Furthermore, the hyperoxia + Dxp group had lower tumor necrosis factor-α and interleukin-1ß median levels compared to the hyperoxia group (p = 0.007). CONCLUSION: Dxp treatment results in less emphysematous change as well as decrease in inflammation and oxidative stress markers in an animal model of BPD.


Assuntos
Lesão Pulmonar/prevenção & controle , Ácido Pantotênico/análogos & derivados , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Hiperóxia/complicações , Pulmão/patologia , Lesão Pulmonar/enzimologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo , Ácido Pantotênico/uso terapêutico , Gravidez , Distribuição Aleatória , Ratos Wistar
18.
J Pediatr Surg ; 50(7): 1119-24, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25783305

RESUMO

BACKGROUND/PURPOSE: In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC. METHODS: Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically. RESULTS: Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1ß in the NEC+Dxp group (p=0.002 and p=0.01, respectively). CONCLUSIONS: Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Enterocolite Necrosante/prevenção & controle , Ácido Pantotênico/análogos & derivados , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Temperatura Baixa , Modelos Animais de Doenças , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/patologia , Glutationa Peroxidase/metabolismo , Hipóxia/complicações , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Malondialdeído/análise , Oxidantes , Estresse Oxidativo/efeitos dos fármacos , Ácido Pantotênico/uso terapêutico , Ratos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Ren Fail ; 36(10): 1570-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25156619

RESUMO

BACKGROUND: We investigated the anti-inflammatory and protective effects of concomitant use of dexpanthenol (DXP) and N-acetylcysteine (NAC) induced ischemia/reperfusion (I/R) injury of kidney. METHODS: Forty rats were randomly divided into 5 groups. In all groups except for Group 1(Sham), renal arteries bilaterally occluded with vascular clamp for IR injury. Group 1(Sham), received a single dose of 10 mL/kg isotonic saline daily by intraperitoneal (IP) injection for three days. Group 2(IR), received a single dose of 10 mL/kg isotonic saline daily by IP injection for three days. Group 3(IR + NAC), received 300 mg/kg NAC daily by IP injection for three days. Group 4(IR + DXP), received 500 mg/kg DXP daily by IP injection for three days. Group 5(IR + NAC + DXP), received 500 mg/kg DXP and 300 mg/kg NAC daily by IP injection for three days. Serum urea (BUN), creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2, siderocalin) levels were measured as kidney function tests. TNF-α levels were measured as inflammatory marker. Tissue sections were evaluated histopathologically under light microscopy. RESULTS: IR + NAC + DXP group received both NAC and DXP before induction of renal I/R and as the biochemical and histopathological data revealed the results of the IR + NAC + DXP group and sham group were similar. Biochemically and histopathologically, combined use of NAC and DXP has better results when each of them used alone. CONCLUSION: We concluded that concomitant use of DXP and NAC plays a major role against I/R injury and may be useful in acute treatment of I/R induced renal failure.


Assuntos
Acetilcisteína/uso terapêutico , Injúria Renal Aguda/prevenção & controle , Sequestradores de Radicais Livres/uso terapêutico , Ácido Pantotênico/análogos & derivados , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/patologia , Animais , Avaliação Pré-Clínica de Medicamentos , Rim/patologia , Masculino , Ácido Pantotênico/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/patologia
20.
Eur J Oncol Nurs ; 18(5): 499-504, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24877859

RESUMO

PURPOSE: Dermatitis is a very frequent and distressing side effect of radiation therapy that may necessitate a treatment interruption when evolving towards more severe forms such as moist desquamation (MD). The aim of this study was to compare the efficacy of two topical agents, a dexpanthenol cream vs a hydroactive colloid gel combining absorbing and moisturising properties, in preventing MD in breast cancer patients. METHODS: This retrospective study compared two successive groups of breast cancer patients undergoing radiotherapy after breast-sparing surgery between 2008 and 2012. A group of 267 patients applied a 5% dexpanthenol cream on the irradiated zone throughout the course of their radiotherapy. Another group of 216 patients applied first the dexpanthenol cream then replaced it by the hydroactive colloid gel after 11-14 days of radiotherapy. Radiation treatment (total dose, technique, and equipment) was the same for the two groups. The clinical outcomes were the occurrence and time to onset of moist desquamation. KEY RESULTS: The overall incidence of MD was significantly lower in patients who applied the hydroactive colloid gel (16%) than in those who applied the dexpanthenol cream (32%, odds-ratio = 0.35). Also, MD occurred significantly later with the hydroactive colloid gel than with the dexpanthenol cream (hazard ratio = 0.39). CONCLUSIONS: Compared with the dexpanthenol cream, the hydroactive colloid gel significantly reduced the risk of developing MD in patients undergoing radiotherapy for breast cancer. These promising results warrant further research on the efficacy of hydroactive colloid gels in managing radiation dermatitis.


Assuntos
Neoplasias da Mama/radioterapia , Coloides/uso terapêutico , Ceratolíticos/uso terapêutico , Ácido Pantotênico/análogos & derivados , Radiodermite/tratamento farmacológico , Radiodermite/etiologia , Radioterapia Adjuvante/efeitos adversos , Administração Tópica , Adulto , Idoso , Feminino , Géis/uso terapêutico , Humanos , Pessoa de Meia-Idade , Ácido Pantotênico/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
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