RESUMO
Although humans are frequently exposed to multiple pollutants simultaneously, research on their harmful effects on health has typically focused on studying each pollutant individually. Inorganic arsenic (As) and benzo[a]pyrene (BaP) are well-known pollutants with carcinogenic potential, but their co-exposure effects on breast cancer cell progression remain incompletely understood. This study aimed to assess the combined impact of BaP and As on the viability and migration of MDA-MB-231 cells. The results indicated that even at low levels, both inorganic As (0.01 µM, 0.1 µM, and 1 µM) and BaP (1 µM, 2.5 µM), individually or in combination, enhanced the viability and migration of the cells. However, the cell cycle analysis revealed no significant differences between the control group and the cells exposed to BaP and As. Specifically, exposure to BaP alone or in combination with As (As 0.01 µM + BaP 1 µM) for 24 h led to a significant increase in vimentin gene expression. Interestingly, short-term exposure to As not only did not induce EMT but also modulated the effects of BaP on vimentin gene expression. However, there were no observable changes in the expression of E-cadherin mRNA. Consequently, additional research is required to evaluate the prolonged effects of co-exposure to As and BaP on the initiation of EMT and the progression of breast cancer.
RESUMO
Understanding the intricate molecular mechanisms governing aryl hydrocarbon receptor (AHR) and Wnt/ß-Catenin pathways crosstalk is of paramount importance for elucidating normal development. We investigated the repercussions of aberrant activation of these signaling pathways on kidney development. HEK-293 cells were subjected to AHR and Wnt activators and inhibitors for 3 and 24 h. Subsequently, pregnant adult female BALB/c mice were administered treatments at gestation day 9 (GD-9), and embryos were analyzed at GD-18 using a combination of cellular, molecular, stereological, and histopathological techniques. Our results demonstrated a noteworthy escalation in oxidative stress and gene expression endpoints associated with apoptosis. Moreover, stereological analyses exhibited alterations in cortex, proximal tubule, and kidney tissue vessels volumes. Remarkably, co-treatment with 6-formylindolo [3,2-b] carbazole (FICZ) and cadmium (Cd) resulted in a significant reduction in glomerulus volume, while elevating the volumes of distal tubule, Henle loop, and connective tissue, compared to the control group. Histopathological investigations further confirmed structural changes in the loop of Henle and proximal tubule, alongside a decline in glomerular volume. Additionally, the expression levels of AHR and Ctnnb1 genes significantly increased in the Cd-treated group compared to the control group. Enhanced expression of apoptosis-related genes, including Bcl-x, Bax, and Caspase3, along with alterations in mitochondrial membrane potential and cytochrome C release, was observed. In contrast, Gsk3 gene expression was significantly decreased. Our findings robustly establish that chemical pollutants, such as Cd, disrupt the AHR and Wnt/ß-Catenin physiological roles during developmental stages by inhibiting the metabolic degradation of FICZ.
Assuntos
Poluentes Ambientais , Rim , Camundongos Endogâmicos BALB C , Receptores de Hidrocarboneto Arílico , Via de Sinalização Wnt , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Animais , Rim/metabolismo , Rim/efeitos dos fármacos , Humanos , Feminino , Via de Sinalização Wnt/efeitos dos fármacos , Camundongos , Poluentes Ambientais/toxicidade , Células HEK293 , beta Catenina/metabolismo , Gravidez , Carbazóis/farmacologia , Cádmio/toxicidade , Apoptose/efeitos dos fármacosRESUMO
This study aims to explore the potential health risks linked to four heavy metals/metalloids (Pb, Cd, As, Hg) present in four commercially important fish species (Scombromorus commerson, Pseudorhombus elevatus, Thunnus tonggol and Otolithes ruber) in the Persian Gulf. Metals in fish muscle tissue were analyzed via ICP-MS. The analysis revealed that Scombromorus commerson (except for Pb) and Thunnus tonggol (except for As) exhibited the highest and lowest contamination levels, respectively. The Hazard Index findings highlighted arsenic and mercury as the most hazardous elements. However, the Target Hazard Quotient values for each metal and fish species remained within safe thresholds. The highest and lowest Total Carcinogenic Risk was concerning Pseudorhombus elevates (As: 7.41-E05), and Thunnus thonggol (Pb: 3.21-E07), respectively. TCR analysis suggests that the cancer risk of studied metals was below the negligible level (TCR < 10-6) or within the acceptable level (10-6 < TCR < 10-4), potentially not posing carcinogenic risks through extended consumption.
Assuntos
Monitoramento Ambiental , Peixes , Metais Pesados , Poluentes Químicos da Água , Metais Pesados/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Oceano Índico , Medição de Risco , Animais , Arsênio/análiseRESUMO
Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.
Assuntos
Caderinas , Calcimiméticos , Cinacalcete , Interleucina-6 , Óxido Nítrico , Ratos Wistar , Receptores de Detecção de Cálcio , Pele , Animais , Cinacalcete/farmacologia , Cinacalcete/uso terapêutico , Masculino , Óxido Nítrico/metabolismo , Calcimiméticos/farmacologia , Receptores de Detecção de Cálcio/metabolismo , Receptores de Detecção de Cálcio/antagonistas & inibidores , Interleucina-6/metabolismo , Caderinas/metabolismo , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Fator de Necrose Tumoral alfa/metabolismo , Ratos , Retalhos Cirúrgicos/patologia , Cicatrização/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sobrevivência de Enxerto/efeitos dos fármacosRESUMO
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. MATERIALS & METHODS: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5â¯mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3â¯mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5â¯mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-ß), and transforming growth factor-ß (TGF-ß) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. RESULTS: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1ß, and TGF-ß, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1ß levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3â¯mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. CONCLUSION: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.
Assuntos
Actinas , Bleomicina , Inflamação , Estresse Oxidativo , Fibrose Pulmonar , Ratos Wistar , Sumatriptana , Animais , Bleomicina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Masculino , Sumatriptana/farmacologia , Ratos , Actinas/metabolismo , Inflamação/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismoRESUMO
This study investigated the efficacy of using chitosan/alginate nanoparticles loaded with recombinant human bone morphogenetic-2 (rhBMP-2) and SMAD4 encoding plasmid to enhance the chondrogenesis of human bone marrow mesenchymal stem cells (hBM-MSCs) seeded on an extracellular matrix (ECM). The research treatments included the stem cells treated with the biological cocktail (BC), negative control (NC), hBM-MSCs with chondrogenic medium (MCM), hBM-MSCs with naked rhBMP-2 and chondrogenic medium (NB/C), and hBM-MSCs with naked rhBMP-2 and chondrogenic medium plus SMAD4 encoding plasmid transfected with polyethyleneimine (PEI) (NB/C/S/P). The cartilage differentiation was performed with real-time quantitative PCR analysis and alizarin blue staining. The data indicated that the biological cocktail (BC) exhibited significantly higher expression of cartilage-related genes compared to significant differences with MCM and negative control (NC) on chondrogenesis. In the (NB/C/S/P), the expression levels of SOX9 and COLX were lower than those in the BC group. The expression pattern of the ACAN gene was similar to COL2A1 changes suggesting that it holds promising potential for cartilage regeneration.