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1.
J Appl Toxicol ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39275926

RESUMO

Alzheimer's disease (AD) is increasingly recognized as a metabolic disorder, often referred to as type 3 diabetes, due to its strong association with insulin resistance. Chronic exposure to aluminum, a known neurotoxin, has been identified as a significant risk factor in the development and progression of AD. This study explores the potential of metformin, a common anti-diabetic drug, to mitigate aluminum-induced neurotoxicity in an in vitro model of AD. Our findings reveal that metformin significantly reduces oxidative stress markers such as malonaldehyde, carbonyl groups, and reactive oxygen species while enhancing antioxidant defenses. Metformin modulates critical signaling pathways, including glycogen synthase kinase 3 beta (GSK3-ß)/RAC-alpha serine/threonine protein kinase (RAC-alpha serine/threonine protein kinase (Akt1)/protein phosphatase 2A (PP2A) and Wnt/ß-catenin, decreasing Tau protein levels and promoting neurogenesis. These results suggest that metformin may offer a novel therapeutic approach for AD, particularly in cases where aluminum exposure is a contributing factor.

2.
J Appl Toxicol ; 44(4): 609-622, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37989595

RESUMO

Alzheimer's disease (AD) is a progressive neurological disorder that affects various cognitive functions, behavior, and personality. AD is thought to be caused by a combination of genetic and environmental factors, including exposure to aluminum (Al). Virgin coconut oil (VCO) may have potential as a natural neuroprotectant against AD. Aim of this study was to determine neuroprotective effects of VCO on Al-induced neurotoxicity in an in vitro AD model. SH-SY5Y cells were initially cultured in normal growth medium and then differentiated by reducing fetal bovine serum content and adding retinoic acid (RA). Later, brain-derived neurotrophic factor (BDNF) was added along with RA. The differentiation process was completed on the seventh day. Study groups (n = 3) were designed as control group, VCO group, Al group, Al-VCO group, Alzheimer model (AD) group, AD + Al-exposed group (AD+Al), AD + VCO applied group (AD + VCO) and AD + Al-exposed + VCO applied group (AD + Al + VCO). Specific markers of AD (hyperphosphorylated Tau protein, amyloid beta 1-40 peptide, and amyloid precursor protein) were measured in all groups. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl, and reactive oxygen species) and neurotransmitter-related parameters (dopamine, dopamine transporter acetylcholine, and synuclein alpha levels, acetylcholinesterase activity) were measured comparatively in the study groups. VCO reduced amyloid beta and hyperphosphorylated Tau protein levels in the study groups. In addition, oxidative stress levels decreased, and neurotransmitter parameters improved with VCO. Our study shows that VCO may have potential therapeutic effects in Alzheimer's disease and further experiments are needed to determine its efficacy.


Assuntos
Doença de Alzheimer , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Óleo de Coco/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Alumínio/toxicidade , Peptídeos beta-Amiloides/toxicidade , Acetilcolinesterase/metabolismo , Neurotransmissores
3.
Drug Chem Toxicol ; : 1-12, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38221775

RESUMO

Aluminum (Al) is a known neurotoxic trace element linked to Alzheimer's disease (AD). Naltrexone, an opioid antagonist, has shown promising effects in reducing neuroinflammation at lower doses than those prescribed for addiction. This study aimed to determine the neuroprotective effects of naltrexone on Al-induced neurotoxicity in an in vitro AD model. The SH-SY5Y cells were first cultivated in a standard growth medium. Subsequently, the cells were induced to differentiate by decreasing the concentration of fetal bovine serum and introducing retinoic acid (RA) into the culture media. Subsequently, the inclusion of brain-derived neurotrophic factor (BDNF) was implemented in conjunction with RA. The process of differentiation was concluded on the seventh day. Study groups (n = 3) were designed as the control group, naltrexone group, Al group, Al-Nal group, Alzheimer' model (AD) group, Alzheimer model + Al-exposed group (AD-Al), Alzheimer model + Nal applied group (AD-Nal) and Alzheimer model + Al-exposed + Nal applied group (AD-Al-Nal). Hyperphosphorylated Tau protein as the specific marker of AD was measured in all groups. Glycogen synthase kinase-3 (GSK-3)ß, Protein phosphatase 2A (PP2A), Akt and Wnt signaling pathways were analyzed comparatively. In addition, oxidative stress parameters (total antioxidant capacity, lipid peroxidase, protein carbonyl and reactive oxygen species) were measured comparatively in the study groups. The results showed that naltrexone reduced hyperphosphorylated tau protein levels by regulating GSK-3ß, PP2A, Akt and Wnt signaling. Also, exposure to naltrexone decreased oxidative stress parameters. Based on these results, naltrexone shows promise as a potential therapy for AD, subject to additional clinical assessments.

4.
Toxicol Mech Methods ; 34(2): 109-121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37794599

RESUMO

Nanoparticles (NPs) are particles of matter that are between 1 to 100 nm in diameter. They are suggested to cause toxic effects in both humans and environment thorough different mechanisms. However, their toxicity profile may be different from the parent material. Titanium dioxide (TiO2) NPs are widely used in cosmetic, pharmaceutical and food industries. As a white pigment, the use of TiO2 is used in food coloring, industrial paints, clothing and UV filters has increased tremendously in recent years. Melatonin, on the other hand, is a well-known antioxidant and may prevent oxidative stress caused by a variety of different substances, including NPs. In the current study, we aimed to comparatively investigate the effects of normal-sized TiO2 (220 nm) and nano-sized TiO2 (21 nm) on cytopathology, cytotoxicity, oxidative damage (lipid peroxidation, protein oxidation and glutathione), genotoxicity (8-hydroxydeoxyguanosine), apoptosis (caspase 3, 8 and 9) and epigenetic alterations (global DNA methylation, H3 acetylation) on 3T3 fibroblast cells. In addition, the possible protective effects of melatonin, which is known to have strong antioxidant effects, against the toxicity of TiO2 were also evaluated. Study groups were: a. the control group; b. melatonin group; c. TiO2 group; d. nano-sized TiO2 group; e. TiO2 + melatonin group and f. nano-sized TiO2 + melatonin group. We observed that both normal-sized and nano-sized TiO2 NPs showed significant toxic effects. However, TiO2 NPs caused higher DNA damage and global DNA methylation compared to normal-sized TiO2 whereas normal-sized TiO2 led to lower H3 acetylation vs. TiO2 NPs. Melatonin showed partial protective effect against the toxicity caused by TiO2 NPs.


Assuntos
Melatonina , Nanopartículas Metálicas , Nanopartículas , Humanos , Melatonina/farmacologia , Nanopartículas Metálicas/toxicidade , Nanopartículas/toxicidade , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Titânio/toxicidade , Dano ao DNA
5.
J Appl Toxicol ; 43(12): 1793-1805, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37409350

RESUMO

Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)-induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK-3ß and the Wnt signaling pathways. The SH-SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK-3ß pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK-3ß, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/ß-catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA-treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK-3ß pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients.


Assuntos
Doença de Alzheimer , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Alumínio/toxicidade , Glicogênio Sintase Quinase 3 beta , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Alzheimer/tratamento farmacológico
6.
J Appl Toxicol ; 43(9): 1368-1378, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36999203

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder that causes memory loss and dementia and is characterized by a decline in cognitive functions. Brain infections, especially induced by herpes simplex virus type-1 (HSV-1), are suggested to play a key role in the pathogenesis of AD. Within the scope of this study, two different AD models (Tau model and amyloid beta [Aß]) were created in the SH-SY5Y cell line, and HSV glycoprotein B (gB) was applied to the cell line and on the generated AD models. Study groups (n = 3) were designed as (1) control, (2) HSV-gB group, (3) retinoic acid (RA) and brain derived neurotrophic factor (BDNF) induced Alzheimer's model (AD), (4) RA and BDNF induced Alzheimer's model + HSV-gB (ADH), (5) Aß 1-42 peptide-induced Alzheimer's model (Aß), and (6) Aß 1-42 peptide-induced Alzheimer's model + HSV-gB (AßH). Levels of complement proteins and cytokines were determined comparatively. In addition, specific markers of AD (hyperphosphorylated Tau proteins, Aß 1-40 peptide and amyloid precursor protein) were measured in all groups. HSV-gB administration was found to increase Aß and hyperphosphorylated Tau levels, similar to AD models. In addition, our data confirmed that the immune system and chronic inflammation might have a crucial role in AD development and that HSV-1 infection might also be an underlying factor of AD.


Assuntos
Doença de Alzheimer , Herpes Simples , Neuroblastoma , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/toxicidade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas , Herpes Simples/metabolismo , Glicoproteínas , Proteínas do Sistema Complemento
7.
Drug Chem Toxicol ; 46(2): 314-322, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35045766

RESUMO

Bisphenol A (BPA) BPA is an endocrine-disrupting chemical that has a wide range of uses. Exposure to BPA can be by oral, inhalation, and parenteral routes. Although its use in several products is limited, there is still concern on its adverse health effects, particularly for susceptible populations like children. Alternative bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are now being used instead of BPA, although there is little information on the toxicity of these bisphenols. BPF is used as a plasticizer in the production of several industrial materials as well as in the coating of drinks and food cans. BPS is used in curing fast-drying epoxy glues, as a corrosion inhibitor and as a reactant in polymer reactions. In this study, the possible toxic effects of BPA, BPS, and BPF in HepG2 cells were evaluated comparatively. For this purpose, their effects on cytotoxicity, production of intracellular reactive oxygen species (ROS), oxidant/antioxidant parameters, and DNA damage have been examined. The cytotoxicity potentials of different bisphenols were found to be as BPS > BPF > BPA. All bisphenol derivatives caused increases in intracellular ROS production. We observed that all bisphenol derivatives cause an imbalance in some oxidant/antioxidant parameters. Bisphenols also caused significant DNA damage in order of BPF > BPA > BPS. We can suggest that both of the bisphenol derivatives used as alternatives to BPA also showed similar toxicities and may not be considered as safe alternatives. Mechanistic studies are needed to elucidate this issue.


Assuntos
Antioxidantes , Estresse Oxidativo , Criança , Humanos , Antioxidantes/farmacologia , Células Hep G2 , Oxidantes , Espécies Reativas de Oxigênio
8.
Int J Environ Health Res ; : 1-10, 2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38007699

RESUMO

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT4) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (ß = 0.26; p = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health.

9.
J Appl Toxicol ; 42(6): 981-994, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34874569

RESUMO

Short-chained alkyl mercury compounds accumulate in particularly in the brain. Exposure to these compounds is associated with various neurotoxic effects. Gender-based differences are observed in neurodevelopmental disorders, and testosterone and estradiol may alter the toxic effect of the compounds. The present study aimed to investigate the toxic effects of methylmercury and thimerosal on SH-SY5Y cells in high testosterone/low estradiol and high estradiol/low testosterone containing cellular environment and estimate whether male and female brains react differently to the toxic effects of methylmercury and thimerosal. Study groups (n = 3) were designed as control: growth medium, thimerosal (T): 1.15-µM thimerosal, methylmercury (M): 2.93-µM methylmercury, high testosterone/low estradiol + thimerosal (TT): 1-µM testosterone + 0.75-µM estradiol + 1.15-µM thimerosal, high estradiol/low testosterone + thimerosal (ET): 0.1-µM testosterone + 7.5-µM estradiol + 1.15-µM thimerosal, high testosterone/low estradiol + methylmercury (TM): 1-µM testosterone + 0.75-µM estradiol + 2.93-µM methylmercury and high estradiol/low testosterone + methylmercury (EM): 0.1-µM testosterone + 7.5-µM estradiol + 2.93-µM methylmercury. While a significant decrease in glutathione levels was observed in M group, it was not seen in EM group. A significant increase in the protein carbonyl levels was detected in T group. A similar increase was observed in the TM and TT groups in which testosterone was dominant. It was determined that methylmercury, but not thimerosal, caused significant DNA damage and in TT group. The results showed that both thimerosal and methylmercury are toxic on SH-SY5Y cells and toxic effects of methylmercury are more severe than thimerosal. It has been determined that testosterone and estradiol alter the toxic effects of thimerosal and methylmercury.


Assuntos
Compostos de Metilmercúrio , Neuroblastoma , Linhagem Celular Tumoral , Estradiol , Feminino , Humanos , Masculino , Compostos de Metilmercúrio/toxicidade , Testosterona , Timerosal/toxicidade
10.
Drug Chem Toxicol ; : 1-11, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36571147

RESUMO

This study aimed to estimate and compare dietary exposure to bisphenol A (BPA) in exclusively breastfed (EBF) and breastfed plus formula-fed (BF + FF) infants. A total of 70 mothers and their 0-6 month-old infants (40 in the EBF group and 30 in BF + FF group) were included in the study. After the questionnaire form was applied to the mothers, maternal breast milk, infant formula, and infant urine were collected from mother-infant dyads. Total BPA levels in breast milk, infant formula, and infant urine samples were analyzed by the high-pressure liquid chromatography (HPLC). While BPA was detected in 92.5% of the breast milk samples in the EBF group (mean ± SD = 0.59 ± 0.29 ng/mL), BPA was detected in all of the breast milk samples in the BF + FF group (mean ± SD= 0.72 ± 0.37 ng/mL) (p < 0.05). Similarly, 100% of the infant formula samples in the BF + FF group had detectable levels of BPA (mean ± SD = 7.54 ± 1.77 ng/g formula). The mean urinary BPA levels in the EBF infants (4.33 ± 1.89 µg/g creatinine) were not statistically different from the BF + FF infants (5.81 ± 0.11 µg/g creatinine) (p > 0.05). The average daily BPA intake in EBF infants (0.18 ± 0.13 µg/kg body weight (bw)/day) was found to be significantly higher than in BF + FF infants (0.12 ± 0.09 µg/kg bw/day) (p < 0.05). The estimated dietary intakes of BPA for infants in both groups were below the temporary tolerable daily intake (t-TDI) (4 µg/kg bw/day). Consequently, BPA intake of EBF and BF + FF infants were within safe daily limits during the first six months of life.

11.
Int J Environ Health Res ; : 1-15, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36519276

RESUMO

The case-control study aimed to evaluate potential sources of exposure and the plasma concentrations of bisphenol A (BPA) and phthalates in prepubertal children having cerebral palsy (CP) and healthy control. Blood samples of 68 CP and 70 controls were analyzed for BPA, di-(2-ethylhexyl)-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and dibutyl phthalate (DBP). BPA and DBP levels were similar in groups. The median DEHP and MEHP levels of the children with CP were significantly lower than those of the controls (p = 0.035, p < 0.001, respectively). Exposure to plastic food containers/bags, personal care hygiene products, household cleaners, wood/coal stove heating, and city water supplies were associated with increased odds of higher BPA and phthalate levels in children with CP. In conclusion, potential exposure sources for BPA and phthalates differ in children with CP and healthy controls, and children with CP are not exposed to higher levels of BPA and phthalates.

12.
Nutrients ; 16(14)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39064718

RESUMO

Bisphenols are endocrine-disrupting chemicals used in plastics and resins for food packaging. This study aimed to evaluate the exposure to bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) associated with the consumption of fresh, canned, and ready-to-eat meals and determine the effects of bisphenols on blood pressure and heart rate. Forty-eight healthy young adults were recruited for this study, and they were divided into the following three groups: fresh, canned, and ready-to-eat meal groups. Urine samples were collected 2, 4, and 6 h after meal consumption, and blood pressure and heart rate were measured. The consumption of ready-to-eat meals significantly increased urine BPA concentrations compared with canned and fresh meal consumption. No significant difference in BPS and BPF concentrations was observed between the groups. The consumption of ready-to-eat meals was associated with a significant increase in systolic blood pressure and pulse pressure and a marked decrease in diastolic blood pressure and heart rate. No significant differences were noted in blood pressure and heart rate with canned and fresh meal consumption. It can be concluded that total BPA concentration in consumed ready-to-eat meals is high. High BPA intake causes increase in urinary BPA concentrations, which may, in turn, lead to changes in some cardiovascular parameters.


Assuntos
Compostos Benzidrílicos , Pressão Sanguínea , Frequência Cardíaca , Fenóis , Sulfonas , Humanos , Fenóis/urina , Compostos Benzidrílicos/urina , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Adulto Jovem , Masculino , Feminino , Adulto , Sulfonas/urina , Alimentos em Conserva , Disruptores Endócrinos/urina , Fast Foods , Contaminação de Alimentos/análise , Embalagem de Alimentos
13.
Nutrients ; 16(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39339813

RESUMO

BACKGROUND: Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal care products, baby bottles, and food packaging. METHODS: In this study, we evaluated the possible routes of exposure to these EDCs in patients diagnosed with PKU (n = 105, 2-6 years of age) and determined the relationship between the plasma levels of bisphenol A (BPA), bisphenol F (BPF), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), mono-(2ethylhexyl) phthalate (MEHP), and dietary regimens. Participant characteristics and exposure routes were evaluated according to their dietary treatment status. RESULTS: Thirty-four of these patients were on a Phe-restricted diet, while the remaining 71 had no dietary restrictions. DBP and DEHP levels were higher in those using plastic tablecloths (p = 0.049 and p = 0.04, respectively). In addition, plasma DBP levels were higher in those who used bottled water (p = 0.01). Being under 4 years of age, using plastic food containers, and using plastic shower curtains were characteristics associated with higher MEHP levels (p = 0.027, p = 0.019, and p = 0.014, respectively). After adjustment for baseline characteristics (Model 1), the odds of having a plasma BPA level in the upper tertile were 3.34 times higher in the free-diet group (95% CI = 1.09-10.25). When we additionally adjusted for plastic exposure (Model 2), the odds ratio was found to be 18.64 (95% CI = 2.09-166.42) for BPA. In the free-diet group, the probability of having plasma DEHP levels in the upper tertile was increased by a relative risk of 3.01 (p = 0.039, 95% CI = 1.06-8.60). CONCLUSION: Our results indicate that exposure to bisphenols and phthalates varies with dietary treatment. The difference in sources of exposure to EDCs between the diet and non-diet groups indicates that diet plays an important role in EDC exposure.


Assuntos
Compostos Benzidrílicos , Fenóis , Fenilcetonúrias , Ácidos Ftálicos , Humanos , Fenóis/sangue , Fenóis/efeitos adversos , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/efeitos adversos , Fenilcetonúrias/sangue , Masculino , Feminino , Ácidos Ftálicos/sangue , Ácidos Ftálicos/efeitos adversos , Pré-Escolar , Criança , Disruptores Endócrinos/sangue , Disruptores Endócrinos/efeitos adversos , Embalagem de Alimentos , Dietilexilftalato/sangue , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Dieta , Fenilalanina/sangue , Estado Nutricional
14.
Nutrients ; 16(20)2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39458458

RESUMO

Background/Objectives: Heavy metals are a group of metals and metalloids that have a relatively high density. They can cause toxicity even at very low levels. Trace elements are required by all living organisms to maintain their normal growth, metabolism, and development. Oral intake is the main route of exposure to both heavy metals and trace elements. Phenylketonuria (PKU) is the most common amino acid metabolic disorder, and the best known treatment for patients requiring treatment is a phenylalanine (Phe)-restricted diet. The objective of the present study was to evaluate the plasma heavy metal levels, sources of exposure, changes in these levels according to dietary regimen, and trace element levels and their correlations with heavy metals in PKU patients. Methods: The study was conducted between July 2022 and January 2024 on 105 patients aged 2-6 years diagnosed with PKU. Results: The percentage of Pb levels in individuals in the upper quartile increased by 3.47 times (95% CI = 1.07-11.29) in those who consumed canned foods and 7.29 times (95% CI = 1.21-44.03) in those who consumed spring water. The percentage of As levels in the upper tertile increased by a factor of 7.26 (95% CI = 2.09-25.28) in individuals under four years of age and 8.17 times (95% CI = 2.13-31.27) in canned food users. The odds of having blood Cd levels in the upper tertile were 0.09 (95% CI = 0.01-0.96) for those being breastfed for 6-11 months compared to 0-5 months. Zn levels were lower (93.0 vs. 83.6 µg/dL, p = 0.008) in patients on a Phe-restricted diet. Conclusions: The present study did not find a relationship between heavy metal exposure and the dietary treatment status of patients with PKU. Our findings indicate that canned food consumption is a significant contributing factor to heavy metal exposure in PKU patients. Furthermore, our findings revealed a relationship between age, perception of economic level, breastfeeding, kitchen equipment, and water usage and the levels of certain heavy metals.


Assuntos
Metais Pesados , Fenilcetonúrias , Oligoelementos , Humanos , Fenilcetonúrias/sangue , Fenilcetonúrias/dietoterapia , Metais Pesados/sangue , Masculino , Pré-Escolar , Feminino , Criança , Oligoelementos/sangue , Dieta , Fenilalanina/sangue , Alimentos em Conserva
15.
Toxicol Res (Camb) ; 13(4): tfae097, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38957781

RESUMO

Improving the quality of life in elderly patients and finding new treatment options for neurological diseases such as Alzheimer's has become one of the priorities in the scientific world. In recent years, the beneficial effects and therapeutic properties of natural foods on neurological health have become a very remarkable issue. Walnut oil (WO) is a promising nutraceutical, with many phytochemicals and polyunsaturated fatty acids and is thought to be promising in the treatment of many neurological diseases and cognitive deficits, such as Alzheimer's disease (AD). Polyphenolic compounds found in WO enhance intraneuronal signaling and neurogenesis and improve the sequestration of insoluble toxic protein aggregates. The objective of this study was to investigate the potential protective and therapeutic effects of WO in a model of AD induced by retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). In order to achieve this, the experimental groups were formed as follows: Control group, WO group, Alzheimer's disease (AD) group, AD + WO applied group (AD + WO). WO supplementation almost significantly reduced oxidative stress in the ad model, providing 2-fold protection against protein oxidation. Additionally, WO showed a significant reduction in tau protein levels (2-fold), increased acetylcholine (ACh) levels (12%), and decreased acetylcholine esterase (AChE) activity (~50%). Since it has been known for centuries that WO does show any adverse effects on human health and has neuroprotective properties, it may be used in the treatment of AD as an additional nutraceutical to drug treatments.

16.
Toxicol Res (Camb) ; 13(4): tfae127, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39132192

RESUMO

Introduction: Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and "low dose toxicity". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased. Methods: In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-ß) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. In vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects. Conclusion: Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.

17.
J Environ Pathol Toxicol Oncol ; 42(2): 31-48, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36749088

RESUMO

Dental implants are medical devices that are surgically inserted into the patient's jawbone by an orthodontist to act as roots of missing teeth. After the implantation, the maxilla or mandible integrates with the surface of the dental implant. This process, called "osseointegration," is an important period to ensure the long-term use of dental implants and prevent implant failures. Metal implants are the most used implant materials. However, they have disadvantages such as corrosion, metal ion release from metal implant surfaces and associated toxicity. To avoid these adverse effects and improve osseointegration, alternative dental implant materials such as ceramics, polymers, composites, and novel surface modification technologies have been developed. The safety of these materials are also of concern for toxicologists. This review will give general information about dental implant materials, osseointegration and successful implantation process. Moreover, we will focus on the new surface coatings materials for of dental implants and their toxicity and safety concerns will be discussed.


Assuntos
Implantes Dentários , Humanos , Propriedades de Superfície , Osseointegração , Maxila , Mandíbula
18.
Environ Sci Pollut Res Int ; 30(45): 100391-100402, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37626198

RESUMO

The aim was to investigate the association between bisphenol A (BPA), 25-hydroxy vitamin D [25(OH)D], and 1α,25 dihydroxy vitamin D [1,25(OH)2D] levels in the cord blood of newborn babies. BPA was measured by high pressure liquid chromatography (HPLC) and vitamin D levels by commercial ELISA or ECLIA kits. BPA and Vitamin D levels were grouped according to tertile values. In the cord blood, the median 25(OH)D level was 14.9 ng/mL (IQR: 8.5-20.8) and median 1,25(OH)2D level was 53.3 pg/dL (IQR: 42.3-98.4). 25(OH)D levels were < 20 ng/mL in 76.5% of the babies. BPA was detectable in 72.4% of the cord blood samples; median BPA level was 1.57 ng/mL (IQR: < DL-4.05 ng/mL). Frequencies of vitamin D deficiency and frequencies of cases having the highest tertile active vitamin D levels were similar in groups of BPA tertiles in both univariate and multivariate analysis. In conclusion, both BPA exposure and insufficient vitamin D transfer via cord blood are common in newborns. Bisphenol A levels were not correlated with vitamin D levels in cord blood of healthy mother-fetus pairs.


Assuntos
Sangue Fetal , Deficiência de Vitamina D , Lactente , Humanos , Recém-Nascido , Sangue Fetal/química , Vitamina D/análise , Vitaminas
19.
Environ Toxicol Pharmacol ; 98: 104065, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36640921

RESUMO

This study was conducted to estimate the daily dietary intakes of melamine for human milk-fed (HMF) babies and mixed-fed (MF) babies. It was carried out in 70 mother-baby pairs (40 babies in the HMF group and 30 babies in the MF group). Human milk, formula milk, and baby urine samples were collected to assess the dietary exposure of babies. Melamine concentrations were analyzed by using a competitive enzyme-linked immunosorbent assay. Melamine was determined in 82.5 % of the human milk samples in the HMF group (median: 0.75 µg/L) while it was present in 96.7 % of human milk samples (median: 1.25 µg/L) and 96.7 % in formula milk samples (median: 0.95 µg/kg) in the MF group. The mean urinary melamine concentration of HMF babies (1.20 ± 0.21 µg/L) was not significantly different than MF babies (1.35 ± 0.49 µg/L). Melamine exposure was calculated as 0.12 µg/kg bw/day and 0.24 µg/kg bw/day in HMF and MF babies, respectively. Melamine exposure in both groups was below the tolerable daily intake. There were no significant associations between melamine exposure and various features of babies and mothers. As a result, it can be suggested that Turkish babies (aged 0-6 months) are not at risk for high melamine exposure through the diet.


Assuntos
Leite Humano , Triazinas , Lactente , Feminino , Humanos , Ingestão de Alimentos , Dieta , Aleitamento Materno
20.
J Environ Pathol Toxicol Oncol ; 41(3): 45-64, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35993955

RESUMO

On December 2019, the world faced a new pandemic caused by a novel type of coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is named as "coronavirus disease 2019 (COVID-19)." This RNA virus infected millions of people around the world causing millions of deaths. It takes approximately 8-10 years to develop a new drug and it seems hard to have a specific pharmaceutical agent against COVID-19. So far, there is only one drug that has applied for registration. The drugs used in clinics against COVID-19 were approved for malaria, human immunodeficiency syndrome (HIV), influenza A and B, and other viral diseases. All these drugs for COVID-19 treatment are being applied according to "drug repurposing (drug repositioning)" strategy. However, they could cause some severe adverse effects on susceptible populations. In some cases, patients can survive after disease. However, the adverse effects of these drugs may lead to morbidity and mortality later. In this review, drugs used against COVID-19 in clinics, their mechanisms of action and possible adverse effects on susceptible populations will be discussed.


Assuntos
Tratamento Farmacológico da COVID-19 , Antivirais/efeitos adversos , Humanos , Pandemias , SARS-CoV-2
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