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1.
J Dermatolog Treat ; 35(1): 2326171, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38565198

RESUMO

In dry skin (DS), skin-barrier function is easily disturbed and moisturizing factors in the stratum corneum are reduced. Despite being a common condition, DS is often overlooked in patients with advanced age or comorbid diseases. In September 2022, specialists in dermatology and skin care met to discuss unmet needs and management of patients with DS with existing medical conditions or DS induced by ongoing pharmacological treatments. There was consensus about the need to improve the current understanding and management of DS in patients with comorbidities, including type 2 diabetes, chronic kidney disease, radiodermatitis, and photodamaged skin. Clinical guidance related to optimal treatment of DS in patients with advanced age or comorbid diseases is needed. Dexpanthenol-containing emollients have been shown to provide rapid relief from the symptoms and clinical signs of skin inflammation and are well-tolerated and effective in terms of moisturizing and soothing DS and maintaining skin-barrier function. Thus, dexpanthenol-containing emollients may play an important role in future management of DS. Further research is needed to elucidate the efficacy of dexpanthenol across the spectrum of DS, irrespective of comorbidity status or age.


Assuntos
Diabetes Mellitus Tipo 2 , Ictiose , Ácido Pantotênico/análogos & derivados , Humanos , Emolientes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ictiose/tratamento farmacológico , Veículos Farmacêuticos , Comorbidade
2.
An Acad Bras Cienc ; 96(1): e20231143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38597495

RESUMO

Plants used in traditional medicine offer an affordable new alternative in tissue repair therapy. This study aimed to evaluate the effectiveness of the 5% Rhizophora mangle cream compared to the 5% dexpanthenol cream in healing open surgical wounds on the upper eyelid. A total of 18 patients were submitted to the experiment and divided into 2 groups with 9 patients each who used topically and daily 5% dexpanthenol cream (control group) or 5% R.mangle cream (intervention group) for 7 days. Clinical, morphometric and histomorphometric analyses of wounds and surgical procedures for skin removal were performed. In the morphometric analysis, all wounds treated with R.mangle and dexpanthenol creams showed complete macroscopic scars, without inflammatory signs and infection free. The skin hydration values in pre and post application periods of the cream were 43.82 ± 43.93 and 62.12 ± 67.40 respectively. The histomorphometric study showed lower values of epithelium distance in R. mangle group and higher in dexpanthenol group with significant difference between groups (p < 0.05). The R.mangle 5% cream proved to be effective in healing wounds of human upper eyelid skin with a significant improvement in epithelization compared to dexpanthenol 5% cream.


Assuntos
Ácido Pantotênico/análogos & derivados , Rhizophoraceae , Cicatrização , Humanos , Brasil , Pálpebras/cirurgia
3.
mBio ; 15(4): e0029824, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38441000

RESUMO

Observational evidence suggests that human milk oligosaccharides (HMOs) promote the growth of commensal bacteria in early life and adulthood. However, the mechanisms by which HMOs benefit health through modulation of gut microbial homeostasis remain largely unknown. 2'-fucosyllactose (2'-FL) is the most abundant oligosaccharide in human milk and contributes to the essential health benefits associated with human milk consumption. Here, we investigated how 2'-FL prevents colitis in adulthood through its effects on the gut microbial community. We found that the gut microbiota from adult mice that consumed 2'-FL exhibited an increase in abundance of several health-associated genera, including Bifidobacterium and Lactobacillus. The 2'-FL-modulated gut microbial community exerted preventive effects on colitis in adult mice. By using Bifidobacterium infantis as a 2'-FL-consuming bacterial model, exploratory metabolomics revealed novel 2'-FL-enriched secretory metabolites by Bifidobacterium infantis, including pantothenol. Importantly, pantothenate significantly protected the intestinal barrier against oxidative stress and mitigated colitis in adult mice. Furthermore, microbial metabolic pathway analysis identified 26 dysregulated metabolic pathways in fecal microbiota from patients with ulcerative colitis, which were significantly regulated by 2'-FL treatment in adult mice, indicating that 2'-FL has the potential to rectify dysregulated microbial metabolism in colitis. These findings support the contribution of the 2'-FL-shaped gut microbial community and bacterial metabolite production to the protection of intestinal integrity and prevention of intestinal inflammation in adulthood.IMPORTANCEAt present, neither basic research nor clinical studies have revealed the exact biological functions or mechanisms of action of individual oligosaccharides during development or in adulthood. Thus, it remains largely unknown whether human milk oligosaccharides could serve as effective therapeutics for gastrointestinal-related diseases. Results from the present study uncover 2'-FL-driven alterations in bacterial metabolism and identify novel B. infantis-secreted metabolites following the consumption of 2'-FL, including pantothenol. This work further demonstrates a previously unrecognized role of pantothenate in significantly protecting the intestinal barrier against oxidative stress and mitigating colitis in adult mice. Remarkably, 2'-FL-enhanced bacterial metabolic pathways are found to be dysregulated in the fecal microbiota of ulcerative colitis patients. These novel metabolic pathways underlying the bioactivities of 2'-FL may lay a foundation for applying individual oligosaccharides for prophylactic intervention for diseases associated with impaired intestinal homeostasis.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Ácido Pantotênico/análogos & derivados , Adulto , Humanos , Animais , Camundongos , Leite Humano , Colite Ulcerativa/metabolismo , Oligossacarídeos/metabolismo , Colite/prevenção & controle , Inflamação
4.
J Biochem Mol Toxicol ; 38(1): e23622, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38229321

RESUMO

Chronic tobacco use can lead to liver damage and inflammation due to the accumulation of various toxins in the body. This study aimed to investigate the correlation between the molecular mechanisms of nicotine-induced liver injury, the caspase cascade, and the Akt/NF-κB signaling pathway, as well as the protective effects of dexpanthenol (DEX). Male rats were subjected to intraperitoneal injections of nicotine at a concentration of 0.5 mg/kg/day and/or DEX at a concentration of 500 mg/kg/day for 8 weeks. After the treatment period, liver function tests were conducted on serum samples, and tissue samples were analyzed for protein levels of Akt, NF-κB, Bax, Bcl-xL, Caspase-3, and Caspase-9, along with histopathological changes. Additionally, assessments of oxidative stress markers and proinflammatory cytokines were carried out. Nicotine administration led to elevated levels of IL-6, IL-1ß, MDA, TOS, and oxidative stress index, accompanied by decreased TAS levels. Moreover, nicotine exposure reduced the p-Akt/Akt ratio, increased NF-κB, Bax, Caspase-3, and Caspase-9 protein levels, and decreased the antiapoptotic protein Bcl-xL levels. DEX treatment significantly mitigated these effects, restoring the parameters to levels comparable to those of the control group. Nicotine-induced liver injury resulted in oxidative stress, inflammation, and apoptosis, mediated by Bax/Bcl-xL, Caspase-3, Caspase-9, and Akt/NF-κB pathways. Conversely, DEX effectively attenuated nicotine-induced liver injury by modulating apoptosis through NF-κB, Caspase-3, Caspase-9, Bax inhibition, and Bcl-xL activation.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Nicotina , Ácido Pantotênico , Animais , Masculino , Ratos , Anti-Inflamatórios/farmacologia , Apoptose , Proteína X Associada a bcl-2/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Nicotina/efeitos adversos , Estresse Oxidativo , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo
5.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 1105-1114, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37606756

RESUMO

Dexpanthenol (DEX), a subtype of vitamin B5, plays an important role in anabolic reactions, cellular energy and regeneration in the body. Nicotine has been shown to induce kidney damage through the mechanisms of oxidative stress and apoptosis. The purpose of this study was to investigate the potential protective effects of DEX against nicotine-induced kidney damage through modulation of the AKT/Nrf2/HO-1 signaling pathway. Male rats were intraperitoneally administered with 0.5 mg/kg/day nicotine and/or 500 mg/kg/day DEX for 8 weeks. Following administration, renal function tests were conducted on serum samples, and histopathological examinations and analysis of oxidative stress markers and antioxidant enzymes were performed on tissue samples. Protein levels of Akt, Nrf-2, HO-1, Bcl-xL, and Caspase-9 were also evaluated. Nicotine administration resulted in decreased protein levels of p-Akt, Nrf-2, HO-1, and Bcl-xL and increased Caspase-9 protein levels. In addition, nicotine administration caused an increase in MDA, TOS, and OSI levels and a decrease in GSH, GSH-Px, GST, CAT, SOD, and TAS levels. Additionally, BUN and Creatinine levels increased after nicotine administration. DEX administration positively regulated these parameters and brought them closer to control levels. Nicotine-induced kidney injury caused apoptosis and oxidative stress through Caspase-9 activation. DEX effectively prevented nicotine-induced kidney damage by increasing intracellular antioxidant levels and regulating apoptosis through Bcl-xL activation. These findings suggest that DEX has potential as a protective agent against nicotine-induced kidney damage.


Assuntos
Antioxidantes , Ácido Pantotênico/análogos & derivados , Proteínas Proto-Oncogênicas c-akt , Masculino , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Caspase 9/metabolismo , Caspase 9/farmacologia , Nicotina/toxicidade , Nicotina/metabolismo , Estresse Oxidativo , Apoptose , Rim
6.
Contact Dermatitis ; 90(2): 161-168, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37960922

RESUMO

BACKGROUND: Overall adherence in the treatment of chronic dermatoses is poor. Textbooks state an adherence dependence on galenics. TRIAL DESIGN: Prospective, randomized, parallel-grouped, single-blinded (investigator), monocentric clinical trial (phase IV) on the adherence to treatment of chronic mild to moderate hand eczema with topical methylprednisolone aceponate (MPA, Advantan®) in different vehicles. OBJECTIVES AND ENDPOINTS: Primary objective was the assessment of the adherence depending on vehicle type in patients with chronic hand eczema. Secondary objective was improvement after a 4-week treatment period. Primary Endpoint Adherence is defined as the percentage of patients applying at least aimed daily dose. Prescribed daily dose was defined as the planned number of applications per day (1) * surface (measured) * aimed amount per application (mg/cm2 ). Truly applicated daily dose was evaluated as individual mean amount per dose * individual mean number of applications per day. Adherence was assumed, if truly applicated daily dose is at least 75% of the prescribed daily dose and the individual mean number of applications per day is at least 0.85. Secondary Endpoint Efficacy was measured by improvement of Hand Eczema Severity Index (HECSI) and Investigator's Global Assessment (IGA) after a 4-week treatment period and in addition to Quality of Life in Hand Eczema Questionnaire (QOLHEQ) and Visual Analogue Scale (VAS) to assess pruritus. METHODS: Number of participants randomized to each group 40, 80 total. Group 1 MPA-C: Methylprednisolone aceponate 0.1% cream and barrier repair emollient (Bepanthen® Sensiderm). Group 2 MPA-FO: Methylprednisolone aceponate 0.1% fatty ointment and barrier repair emollient (Bepanthen® Sensiderm). Adherence to treatment was compared via Fisher's exact test. RESULTS: Of the patients, 48% were adherent according to our definition. There was no significant difference between MPA-C (42.1%) and MPA-FO (54.1%; p = 0.36; group difference-12.0%, 95% CI-34.3%-11.5%). Generalized-linear-model-analysis of adherence to study treatment with factors emollient use, treatment, time and treatment-time interaction showed a parallel between adherence and amount of emollient use (odds ratio 1.74, p = 0.0038; 95% CI-1.22-2.52). Improvement of hand eczema was seen according to clinical scores without remarkable differences between the groups. CONCLUSIONS: No dependence of adherence on galenics of topical treatment of chronic hand eczema could be proved. Patients who use more emollient tend to be more adherent to the topical treatment.


Assuntos
Dermatite Alérgica de Contato , Eczema , Ácido Pantotênico/análogos & derivados , Humanos , Emolientes/uso terapêutico , Pomadas , Qualidade de Vida , Estudos Prospectivos , Dermatite Alérgica de Contato/tratamento farmacológico , Metilprednisolona , Eczema/tratamento farmacológico , Eczema/induzido quimicamente , Resultado do Tratamento
7.
J Dtsch Dermatol Ges ; 22(2): 198-207, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38092687

RESUMO

BACKGROUND: Radiation dermatitis (RD) remains the most common side effect in radiation therapy (RT) with various pharmaceutical options available for prevention and treatment. We sought to determine pharmaceutical management patterns of radiation dermatitis among radiation oncology professionals. METHODS: We conducted a survey on RD among the German-speaking community of radiation oncologists inquiring for their opinion on preventive and therapeutic pharmaceutical approaches for acute RD. RESULTS: 244 health professionals participated. Dexpanthenol lotion is the agent most widely used both for prevention (53.0%) and treatment (76.9%) of RD, followed by urea (29.8%) for prevention and corticosteroids (46.9%) for treatment. A wide range of substances is used by participants, though the overall experience with them is rather limited. 32.5% of participants do generally not recommend any preventative treatment. 53.4% of participants recommend alternative medicine for RD management. While seldomly used, corticosteroids were considered most effective in RD therapy, followed by dexpanthenol and low-level laser therapy. A majority of participants prefers moist over dry treatment of moist desquamation and 43.8% prescribe antiseptics. CONCLUSIONS: Pharmaceutical management of RD in the German-speaking radiation oncology community remains controversial, inconsistent, and partially not supported by evidence-based medicine. Stronger evidence level and interdisciplinary consensus is required amongst practitioners to improve these care patterns.


Assuntos
Ácido Pantotênico/análogos & derivados , Radioterapia (Especialidade) , Radiodermatite , Humanos , Radiodermatite/tratamento farmacológico , Radiodermatite/prevenção & controle , Corticosteroides/uso terapêutico , Preparações Farmacêuticas
8.
Int J Toxicol ; 41(3_suppl): 77-128, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36177798

RESUMO

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Panthenol, Pantothenic Acid, and 5 derivatives as used in cosmetics. These ingredients named in this report are reported to function in cosmetics as hair conditioning agents, and Panthenol also is reported to function as a skin-conditioning agent-humectant and a solvent. The Panel reviewed relevant data for these ingredients, and concluded that these 7 ingredients are safe in cosmetics in the present practices of use concentration described in this safety assessment.


Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos , Cosméticos/toxicidade , Higroscópicos , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/toxicidade , Medição de Risco , Solventes
10.
J Cosmet Dermatol ; 21(9): 3859-3866, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35866315

RESUMO

BACKGROUND: Gentle cleansing of the skin without further compromising its barrier function and moisture content and being simultaneously devoid of adverse effects on the skin microbiome are important features of body cleansers for atopic-prone skin sufferers. For this population, a new dexpanthenol-containing liquid cleanser (DCLC) was developed. METHODS: Two prospective 4-week studies have been conducted. Study 1 investigated the effect of once-daily DCLC on stratum corneum (SC) hydration, transepidermal water loss (TEWL), skin pH, and skin microbiome (all on the volar forearm) in adult subjects with dry skin (N = 44). Study 2 explored the cutaneous tolerability of DCLC and its effect on the microbiome biodiversity of the volar forearm skin in infants/children with atopic-prone skin (N = 33, aged 6 months to 6 years). In the latter study, DCLC was applied 2-3 days/week in combination with an emollient applied at least twice daily. RESULTS: In Study 1, on Day 29, the mean change in skin surface capacitance from baseline was significantly greater in the forearm test area treated with DCLC than in the contralateral test area (control) treated with water only (5.16 vs. 3.65 a.u.; p = 0.011), suggesting long-term SC hydration. DCLC use was not associated with changes in TEWL, skin pH, or microbiome biodiversity if compared to control. In Study 2, the 4-week use of DCLC in combination with an emollient was well tolerated according to pediatrician skin assessment, and no flare-ups were recorded. The microbiome biodiversity did not shift during the study. CONCLUSION: These findings support the use of DCLC in subjects with atopic-prone skin.


Assuntos
Emolientes , Pele , Adulto , Criança , Humanos , Lactente , Ácido Pantotênico/análogos & derivados , Estudos Prospectivos , Água/metabolismo , Perda Insensível de Água
11.
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
12.
Tissue Cell ; 77: 101824, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35653907

RESUMO

Exposure to various organic compounds including several environmental pollutants and drugs can cause cellular damage through the generation of lipid peroxidation products. Carbon tetrachloride (CCl4) is a potent toxic agent that causes peroxidative degeneration in many tissues. Dexpanthenol (Dxp) is a member of the B complex vitamins that exhibits antioxidant effects against lipid peroxidation products. This study was designed to evaluate the cardioprotective effect of Dxp against CCl4-induced myocardial toxicity in rats. Administration of a single dose of CCl4 caused cardiotoxicity by the increase in lipid peroxidation and histopathological changes (cardiomyocytes degeneration, interstitial edema) in the myocardial tissue. Moreover, CCl4 caused a decrease in lactate dehydrogenase (LDH) and troponin-I immunoreactivities, while significantly increasing tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivities. On the other hand, administration of Dxp improved biochemical, histopathological, and immunohistochemical parameters compared to the CCl4 treated group. Overall, this study suggests that Dxp is effective in inhibiting CCl4-induced lipid peroxidation, and that administration of Dxp may help prevent CCl4 related inflammation, necrosis, and apoptosis on the cardiac tissue.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Tetracloreto de Carbono/metabolismo , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Peroxidação de Lipídeos , Fígado/patologia , Estresse Oxidativo , Ácido Pantotênico/análogos & derivados , Ratos
13.
Bioengineered ; 13(5): 11625-11635, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510377

RESUMO

Sepsis is capable of causing systemic infections resulting in multiple organ damage. Dexpanthenol (DXP) has been reported to protect against kidney and liver injury. Therefore, this paper attempts to explore the role of DXP in sepsis-induced kidney and liver injury. A mice model of sepsis was established using the cecal ligation and puncture (CLP) method. The expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and monocyte chemoattractant protein (MCP)-1 in the serum of mice were measured utilizing enzyme linked immunosorbent assay (ELISA). Additionally, the damage of kidney and liver tissues in CLP-induced mice was determined by their respective commercial kits, western blot, and hematoxylin-eosin (HE) staining kits. The apoptosis of kidney and liver tissues in CLP-induced mice was assessed by means of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and western blot. It was observed that DXP decreased the expressions of TNF-α, IL-1ß, IL-6, and MCP-1 in the serum of CLP-induced mice, attenuated the functional impairment, pathological damage, inflammation, and cell apoptosis of kidney tissue. Meanwhile, DXP decreased the functional impairment of liver in CLP-induced mice, reduced the levels of inflammatory factors and antioxidant enzymes, attenuated liver pathological damage, and decreased cell apoptosis in liver tissues. In conclusion, DXP attenuates inflammatory damage and apoptosis in kidney and liver organs in a sepsis model.


Assuntos
Interleucina-6 , Sepse , Animais , Apoptose , Modelos Animais de Doenças , Interleucina-6/metabolismo , Rim/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ácido Pantotênico/análogos & derivados , Sepse/complicações , Sepse/tratamento farmacológico , Fator de Necrose Tumoral alfa/genética
14.
Int J Exp Pathol ; 103(4): 164-170, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35441448

RESUMO

Wound healing is a dynamic process initiated in response to injury. There are many factors that have detrimental effects on the wound healing process. Numerous studies have been conducted for improving wound healing processes. Dexpanthenol is widely used to accelerate wound healing. Sucralfate is used for the treatment of peptic ulcers. We aimed to compare the efficacy of topical Dexpanthenol and Sucralfate in an experimental wound model in rats via histopathological examinations and immune histochemical determinations, as well, to evaluate their effects on EGF levels. Three different groups were formed: the Control Group, the Dexpanthenol Group and the Sucralfate Group. Full-thickness skin wounds were created on the back of each rat and isotonic saline was applied to the wounds of the rats in the control group, Bepanthol® cream was applied in Dexpanthenol Group and 10% Sucralfate cream was applied in Sucralfate Group, once a day. On the 7th, 14th and 21st days the wounds were measured and seven rats from each group were sacrificed and the wounds were excised for histopathological examination. Sucralfate increased wound healing rates by increasing neovascularization, fibroblast activation, reepithelialization and collagen density, as well as dexpanthenol. Our study revealed that the dexpanthenol and sucralfate groups were better than the control group in terms of their effects on wound healing, however there was no statistically significant difference among these two groups. Sucralfate improves EGF expression in skin wounds and has positive results on skin wound healing comparable to dexpanthenol.


Assuntos
Fator de Crescimento Epidérmico , Sucralfato , Animais , Fator de Crescimento Epidérmico/farmacologia , Ácido Pantotênico/análogos & derivados , Ácido Pantotênico/farmacologia , Ratos , Sucralfato/farmacologia , Cicatrização
15.
Nat Commun ; 13(1): 2158, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35444200

RESUMO

Drug resistance and a dire lack of transmission-blocking antimalarials hamper malaria elimination. Here, we present the pantothenamide MMV693183 as a first-in-class acetyl-CoA synthetase (AcAS) inhibitor to enter preclinical development. Our studies demonstrate attractive drug-like properties and in vivo efficacy in a humanized mouse model of Plasmodium falciparum infection. The compound shows single digit nanomolar in vitro activity against P. falciparum and P. vivax clinical isolates, and potently blocks P. falciparum transmission to Anopheles mosquitoes. Genetic and biochemical studies identify AcAS as the target of the MMV693183-derived antimetabolite, CoA-MMV693183. Pharmacokinetic-pharmacodynamic modelling predict that a single 30 mg oral dose is sufficient to cure a malaria infection in humans. Toxicology studies in rats indicate a > 30-fold safety margin in relation to the predicted human efficacious exposure. In conclusion, MMV693183 represents a promising candidate for further (pre)clinical development with a novel mode of action for treatment of malaria and blocking transmission.


Assuntos
Antimaláricos , Antagonistas do Ácido Fólico , Malária Falciparum , Malária Vivax , Malária , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Camundongos , Ácido Pantotênico/análogos & derivados , Plasmodium falciparum/genética , Ratos
16.
Molecules ; 27(6)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35335123

RESUMO

Curcumin (CUR) and D-panthenol (DPA) have been widely investigated for wound-healing treatment. In order to analyse these two compounds from a dosage form, such as polymer-based wound dressings or creams, an analytical method that allows the quantification of both drugs simultaneously should be developed. Here, we report for the first time a validated high-performance liquid chromatographic (HPLC) method coupled with UV detection to quantify CUR and DPA based on the standards set by the International Council on Harmonization (ICH) guidelines. The separation of the analytes was performed using a C18 column that utilised a mobile phase consisting of 0.001% v/v phosphoric acid and methanol using a gradient method with a run time of 15 min. The method is linear for drug concentrations within the range of 0.39-12.5 µg mL-1 (R2 = 0.9999) for CUR and 0.39-25 µg mL-1 for DPA (R2 = 1). The validated method was found to be precise and accurate. Moreover, the CUR and DPA solution was found to be stable under specific storage conditions. We, therefore, suggest that the HPLC-UV method developed in this study may be very useful in screening formulations for CUR and DPA within a preclinical setting through in vitro release studies.


Assuntos
Curcumina , Bandagens , Cromatografia Líquida de Alta Pressão/métodos , Ácido Pantotênico/análogos & derivados
17.
Immunopharmacol Immunotoxicol ; 44(2): 186-193, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35040389

RESUMO

BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of many psychiatric and neurodegenerative diseases. Dexpanthenol (Dex) is an alcoholic analogue of pantothenic acid with antioxidant, anti-inflammatory and anti-apoptotic properties. The purpose of this study was to determine the effect of dexpanthenol on lipopolysaccharide (LPS)-induced brain injury, specifically on the CREB/BDNF pathway. METHOD: Thirty-two rats were distributed into four groups: control, LPS, LPS + Dex and Dex groups. In this study, using real-time PCR, we evaluated changes in the gene expression of BDNF and CREB in the hippocampal brain tissue. Total antioxidant status (TAS), total oxidant status (TOS) were measured spectrophotometrically in the cortical tissue. Brain and cerebellum tissues were collected for histopathological examination and immunohistochemical assessment of tumor necrosis factor alpha (TNF-α) and caspase-3 (Cas-3). RESULT AND DISCUSSION: In the LPS + Dex group, TAS levels were significantly higher while TOS and OSI levels were significantly lower than the LPS group. In the LPS + Dex and Dex group, BDNF relative mRNA expressions were significantly higher than the LPS group. The levels of CREB relative mRNA expression in LPS and LPS + Dex group were significantly lower than the control group. An increased expression of Cas-3 and TNF-α in the LPS group and a decreased expression in the LPS + Dex group were observed in the immunohistochemical examination. CONCLUSION: According to these results, it may be considered that CREB-mediated BDNF synthesis may play a role in the etiopathogenesis of neuroinflammation. By regulating these changes with dexpanthenol treatment, a positive contribution may be made to neuroinflammation treatment.


Assuntos
Antioxidantes , Lipopolissacarídeos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Hipocampo , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , Ácido Pantotênico/análogos & derivados , Ratos
18.
Int J Pharm ; 611: 121354, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34883208

RESUMO

Topically applied antiviral creams and patches are the commercially available options for the treatment of herpes labialis. The nanofibrous patches could be a new direction in the formulation. The project aimed to formulate core-shell type nanofibrous scaffolds loaded with dexpanthenol (shell) and acyclovir (core). To achieve the fast dissolution of the antiviral agent, hydroxypropyl-beta-cyclodextrin was used as a complexation agent. The further aim was to study the prepared electrospun scaffolds' morphological- and physicochemical properties and antiviral activity. The fibrous samples were prepared by electrospinning using polyvinylpyrrolidone (PVP) as a shell, hypromellose (HPMC), and poly(ethylene oxide)(PEO) composite or poly(vinyl alcohol) (PVA) as a core polymer. The morphology of the prepared sample was studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy. The SEM photos showed that fibrous structures were obtained. In the case of the PVA/PVP composition, the desired structure was obtained. While when HPMC-PEO was used as a core, the core-shell structure could not be observed. The Raman measurements revealed the mixed fibre structure of this sample. All of the fibrous samples released about 100% of acyclovir and also the dexpanthenol within 20 min. Coaxially electrospun fibres of different compositions were successfully prepared with various structural homogeneities, furthermore, a better antiviral activity could be achieved compared to the commercially available Zovirax cream.


Assuntos
Herpes Labial , Nanofibras , Aciclovir , Humanos , Ácido Pantotênico/análogos & derivados , Álcool de Polivinil
19.
Drug Chem Toxicol ; 45(5): 2160-2168, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33874839

RESUMO

AIM: Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined. DESIGN AND METHODS: In total, 18 adult sprague-dawley rats were classified into 3 groups; control (n = 6), STZ + Saline (n = 6) and STZ + Dexpanthenol (n = 6). Twelve AD-induced rats through STZ-injection (3 mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000 mg/kg/day, i.p.) for 3 weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-α) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3). RESULTS: It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-α in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects. CONCLUSION: Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Alzheimer/tratamento farmacológico , Animais , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Hipocampo , Humanos , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Neurônios , Fármacos Neuroprotetores/farmacologia , Ácido Pantotênico/análogos & derivados , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Estreptozocina/toxicidade , Fator de Necrose Tumoral alfa/metabolismo
20.
Biotech Histochem ; 97(1): 39-43, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33632031

RESUMO

Cisplatin (CIS) is an antineoplastic agent used for treating solid organ tumors. Toxic side effects of CIS treatment include nephrotoxicity, neurotoxicity, ototoxicity, myelosuppression and hepatotoxicity. Dexpanthenol (DEX) exhibits antioxidant and anti-inflammatory effects and protective effects against free oxygen radicals. We investigated the protective effects of DEX on CIS induced nephrotoxicity. Animals were divided into four groups of 10. The control group was given saline. The DEX group was treated with DEX for 10 days. The CIS group was treated with a single dose of CIS. The DEX + CIS group was given a single dose of CIS followed by DEX for 10 days. We found increased levels of malondialdehyde (MDA), blood urea nitrogen (BUN) and creatinine, while superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO) levels were decreased in the CIS group. MDA, BUN and creatinine levels were decreased, while SOD, CAT, GPx and MPO levels were increased in the DEX + CIS group. Renal tubule damage, inflammation and histopathology scores were significantly higher in the CIS group than the control. The DEX + CIS group exhibited less renal tubule damage and inflammation, and lower histopathological assessment scores than the CIS group. Significant cortical tubule damage and interstitial inflammation were observed in the CIS group. Tubule damage was slightly less, and mild tubule dilation and less cast formation were observed in the DEX + CIS group; also, inflammation was less severe than for the CIS group. DEX may have therapeutic potential for treating CIS induced nephrotoxicity due to its antioxidant and anti-inflammatory properties.


Assuntos
Cisplatino , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Cisplatino/toxicidade , Creatinina/metabolismo , Glutationa/metabolismo , Rim/metabolismo , Malondialdeído/metabolismo , Ácido Pantotênico/análogos & derivados , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
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