Organochlorine pesticides and epigenetic alterations in thyroid tumors.

Purpose: Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients. Methods: OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis. Results: Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P<0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P<0.001) and H4K16 (OR=6.03, P<0.001) acetylation. Conclusion: The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.

The Diabetic Lung Can Be Ameliorated by Citrullus colocynthis by Reducing Inflammation and Oxidative Stress in Rats with Type 1 Diabetes.

Background: Diabetes impacts various organs in the body and some reports showed that the lung is also affected by diabetes, and an imbalance of inflammation and oxidative stress may participate to diabetic lung impairments. The present study is conducted to assess the impacts of Citrullus colocynthis (CC) on some aspects of these impairments. Methods: Frothy two male Wistar rats (3-4 months old and weighing 200-250 g) were used in the present research. Animals were divided into 3 groups of control, Diabetes, and Diabetes + Drug. CC was administered to diabetic rats orally. The lung tissue and BALF oxidative stress and inflammatory indices including the MDA, TAC, SOD, Gpx, TNFα, IL-6, IL-17, and IL-10 were evaluated by the ELISA method. Results: Our observations disclosed the ameliorative impacts of CC administration against oxidative stress and inflammation imbalance. Also, it was found that CC improved body weight and fasting blood sugar in rats with diabetes. Conclusion: We can conclude that the administration of CC can be effective in improving diabetic lungs in rats.

Pesticide Exposure and Alzheimer's Disease: A Case-control Study.

Aim / Objective: This study aimed to investigate the levels of organochlorine pesticides (OCPs) in the serum of Alzheimer's disease (AD) patients. METHODS: 63 AD patients and 50 healthy individuals participated, and the levels of some OCPs derivatives (including; α-HCH, ß-HCH, γ-HCH, 2,4-DDT, 4,4-DDT, 2,4-DDE, and 4,4-DDE), total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), Nitric oxide (NO) along with the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), paraoxonase 1(PON1), and acetylcholinesterase (AChE) were measured. RESULTS: The mean OCP level of OCPs in AD patients was significantly higher than in the control group. However, the patients' mean levels of TAC, PC, MDA and activity of SOD, GPx, PON1 and AChE were significantly lower than controls. A significant positive correlation was also observed between 2,4-DDE and MDA and between γ-HCH and PC in AD patients. These findings showed that pesticide exposure is associated with an increased risk of AD. Furthermore, the mean levels of oxidative stress markers, which may result from pesticide exposure, were significantly lower in AD patients compared to healthy individuals. CONCLUSION: Therefore, it may conclude that pesticides, at least in part, contribute to AD development through several mechanisms, including the induction of oxidative stress.

Organochlorine pesticides induce thyroid tumors through oxidative stress; an in vivo and in silico study.

Thyroid disease is one of the most common endocrine problems around the world. Among the numerous factors, exposure to environmental elements such as pesticides is associated with an increase in the incidence of thyroid disorders. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) in induction of oxidative stress (OS) and development of thyroid tumors. This case-control study was conducted on 61 patients with papillary thyroid carcinoma (PTC), 70 patients with benign thyroid nodules (BTN), and 73 healthy individuals as control. Seven derived OCPs residues measured by gas chromatography (GC), and enzyme activities of acetylcholinesterase (AChE), superoxide dismutase3 (SOD3), catalase (CAT), glutathione peroxidase3 (GPx3) and paraoxonase1 (PON1) and also, non-enzymatic antioxidant including; malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), and nitric oxide (NO) biomarkers in all participants were investigated. Furthermore, all of the above enzymes were docked against measured OCPs. The results revealed that ß-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4-DDT, and 4,4-DDT levels along with MDA, NO, and PC levels were elevated, while AChE, SOD3, GPx3, CAT, and PON1 activities and TAC levels were decreased in the PTC and BTN groups compared with the control group. Therefore, OCPs might play a role in the development of thyroid tumors through several mechanisms including generation of OS. Importantly, in silico analysis confirmed the in vivo findings.

Perillyl alcohol (PA) mitigates inflammatory, oxidative, and histopathological consequences of allergic asthma in rats.

Allergic asthma is an inflammatory and chronic condition, which is the most common asthma phenotype. It is usually defined by sensitivity to environmental allergens and leads to the narrowing of the airways. Around 300 million individuals are suffering from asthma worldwide. The purpose of the current research was to evaluate the effect of perillyl alcohol (PA) on oxidative stress and inflammation parameters in rats with allergic asthma. Experimental asthma was induced by ovalbumin (OVA) sensitization and inhalation in five groups of rats including control, asthma, asthma + vehicle, asthma + PA, and asthma + dexamethasone (Dexa). PA (50 mg/kg) or Dexa (2.5 mg/kg) were administered intraperitoneally for seven consecutive days following asthma induction. Histopathological evaluation was performed via hematoxylin and eosin (H&E) and Masson's trichrome staining. The enzyme-linked immunosorbent assay (ELISA) was used for the evaluation of the cytokine levels, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-17, and IL-10, as well as oxidative stress biomarkers including reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione peroxidase (GPx) in the lung tissue and bronchoalveolar lavage fluid (BALF). Real-time polymerase chain reaction (PCR) was utilized for assessing the mRNA expression of FOXP3 and GATA3 and western blot analysis was used for the measurement of nuclear factor kappa B (NF-κB) protein expression. PA and Dexa decreased the pathological alterations and the expression levels of inflammatory factors (cytokines, GATA3, and NF-κB) in the lung tissue and BALF of asthmatic rats. PA restored GPx, SOD, and TAC levels and reduced ROS, MDA, nitrite, and total protein in the lung and BALF. Overall, our findings demonstrated that PA can be used as a therapeutic agent in asthma patients, but it is essential to monitor its effects in future clinical studies.

Investigating the effects of Citrullus colocynthis on cognitive performance and anxiety-like behaviors in STZ-induced diabetic rats.

Background: Diabetes can impair cognitive performance and lead to dementia. Patients with type 1 diabetes mellitus (T1DM) are reported with different levels of cognitive dysfunctions in various cognitive domains ranging from general intellectual testing to specific deficits with visuospatial abilities, motor speed, writing, attention, reading, and psychomotor efficiency. The present study aimed to investigate the effect of Citrullus colocynthis on cognitive functions.Methods: A total of 42 male Wistar rats (3-4 months old and weighing 200-250 g) were tested in the current study. Rats were randomly allocated into 3 groups of control, Diabetes, and Diabetes + Drug. The diabetic rats received Citrullus colocynthis extraction orally. The behavioral tests included the open field, elevated plus maze (EPM), novel object recognition (NOR), passive avoidance tests, and Morris Water Maze (MWM) tests. Data were analyzed using student and paired t-tests via SPSS software version 16.Results: Our results showed the protective effects of Citrullus colocynthis administration against cognitive impairments. This is followed by STZ-induced diabetes in the MWM, novel object recognition, and passive avoidance tasks. Also, it was found that Citrullus colocynthis improved anxiety in diabetic rats.Conclusion According to the findings of this study, the administration of 200 mg/kg C. colocynthis once per day for 40 days can lead to ameliorated cognitive impairments and antidiabetic effects such as increasing body weight and decreasing FBS.

Plasma Complement C1q/tumor necrosis factor-related protein 15 concentration is associated with polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common poignant endocrine disorder affecting women, posing a close association with metabolic syndrome and obesity. Existing literature characterizes PCOS with deranged levels of several adipokines and myokines. CTRP15 is a paralogue of adiponectin, mainly expressed by skeletal muscles, and plays a key role in insulin, glucose, and lipid metabolism. In the current study, we aim to determine the circulating levels of CTRP15 and evaluate its association with cardiometabolic and inflammatory parameters in PCOS women. This case-control study included 120 PCOS patients (60 Recurrent pregnancy loss (RPL) and 60 infertile (inf) PCOS) and 60 healthy non-PCOS controls. Serum levels of hs-CRP were measured by commercial kits, while serum levels of adiponectin and CTRP15 were determined using the ELISA technique. Serum levels of CTRP15 were significantly elevated in PCOS-RPL and PCOS-inf subgroups when compared to controls (94.80 ± 27.08 and 87.77 ± 25.48 vs. 54.78 ± 15.45, both P < 0.001). Moreover, serum adiponectin was considerably lower in the PCOS group and subgroups (P < 0.001), while serum hs-CRP, fasting insulin, HOMA-IR, and free testosterone were significantly higher when compared to the non-PCOS group (P < 0.05). Furthermore, CTRP15 closely associated with FSH, HOMA-IR, hs-CRP, and BMI. These results highlight a possible involvement of CTRP15 in the pathogenesis of PCOS. The elevated levels of CTRP15 might be a compensatory mechanism for the metabolic dysregulations (excess adiposity, insulin resistance, metaflammation) associated with the syndrome. Nevertheless, future studies are necessary to unravel the underlying mechanism.

Effects of trehalose on NFE2L2, catalase, and superoxide dismutase in the kidney of aged rats.

Aging is associated with an increase in oxidative stress, which damages organs such as the kidney. Trehalose has abundant beneficial activities including antioxidative effects. This study aimed to investigate the effects of trehalose on several antioxidant parameters of the aged kidney. Wistar rats were divided into three groups: young (4 months), aged (24 months), and aged-trehalose. The third group was treated with 2% trehalose for one month. The expression of target genes and enzyme activities in the kidney of the animals were evaluated by quantitative polymerase chain reaction (qPCR) and enzyme colorimetric procedures, respectively. Protein levels of NFE2L2 showed a 50% reduction in aged rats compared to young rats (P<0.001), which was restored by trehalose intervention. In addition, the activity and mRNA levels of catalase (CAT) increased in aged rats while treatment with trehalose reversed this trend. On the other hand, superoxide dismutase (SOD) activity was reduced in the kidneys of aged rats but was not affected by trehalose intervention .It is concluded that trehalose supplementation alleviates the antioxidant system impairments in the kidneys of aged rats. However, further investigations are needed to thoroughly describe the antioxidative impacts of trehalose on the kidneys during aging.

Evaluation of angiopoietin-like protein 3 (ANGPTL3) levels in polycystic ovary syndrome.

AIM: Angiopoietin-like protein 3 (ANGPTL3) is recognized as a regulator of lipid metabolism. However, little is known about its association with insulin resistance in polycystic ovary syndrome (PCOS) setting. The present study aimed to investigate the serum levels of ANGPTL3 and adiponectin in PCOS women compared to healthy controls. MAIN METHOD: In this study, a total of 175 premenopausal women (117 PCOS and 58 non-PCOS) were enrolled. Serum concentrations of ANGPTL3, adiponectin, fasting insulin, and other hormonal variables were measured using ELISA technique. KEY FINDINGS: Results showed that adiponectin levels were significantly lower in PCOS group than those of non-PCOS group. However, serum levels of ANGPTL3, high-sensitivity C-reactive protein (hs-CRP), and homocysteine (Hcy) were found to be higher in PCOS patients, when compared to non-PCOS ones. Moreover, serum ANGPTL3 positively correlated with BMI and serum triglyceride, while it inversely correlated with serum HDL-C in PCOS patients. SIGNIFICANCE: Our results demonstrated that increased levels of ANGPTL3 correlated with insulin resistance and dyslipidemia in PCOS patients, highlighting the need for future studies targeting its role in the pathogenesis of this disease.

Pesticide exposure and related health problems among family members of farmworkers in southeast Iran. A case-control study.

BACKGROUND: Pesticides used in agriculture are some of the most common pollutants in the world. This study aimed to investigate the effects of Organophosphorus Pesticides (OPPs) and Organochlorine Pesticides (OCPs) on the families of farmworkers in the southeast of Iran. METHODS: In the present case-control study, 141 family members of farmworkers (as the case group) and 59 family members of non-farmworkers (as the controls) were recruited. Serum levels of OCPs such as α-HCH, ß-HCH, γ-HCH, 2,4-DDE, 4,4-DDE, 2,4-DDT, and 4,4-DDT were determined. In addition, erythrocyte acetylcholinesterase (AChE) activity, malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), nitric oxide (NO) serum levels, arylesterase activity of paraoxonase 1 (PON-1), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity were determined in all participants. Furthermore, distance to farmlands, education, crops, type, and the number of consumed fruits were evaluated for each individual separately. RESULTS: The erythrocyte AChE activity and serum activities of GPx, SOD, and PON-1 and TAC levels were significantly decreased, whereas the concentration of MDA, PC, NO, and seven OCPs were significantly increased in the farmworkers' families as compared to the controls. Spearman correlation and linear regression suggest that OCPs increase the oxidative stress in farmworkers' family members. Moreover, distance, education, farming precedence, products, and ventilation had significant effects on the OCP levels and increased the odds ratio of OCP levels in farmworkers' families. CONCLUSION: With regards to the data obtained in this study, it was revealed that OCPs as illegal pesticides and OPPs were higher than expected in the farmworkers' family members. Furthermore, exposure to OCPs and OPPs, apart from the other effects on the body, leads to oxidative stress (OS) that may cause serious diseases in the exposed populations.

Effect of Cerium Oxide Nanoparticles on Oxidative Stress Biomarkers in Rats' Kidney, Lung, and Serum.

Background: The present study aimed to evaluate the effects of different concentrations of cerium oxide nanoparticles (CONPs) on the oxidative stress (OS) status in kidney, lung, and serum of rats. Methods: Male Wistar Rats were treated intraperitoneally with 15, 30, and 60 mg/kg/day of CONPs. The biochemical parameters, including total antioxidant capacity (TAC), total thiol group (TTG), malondialdehyde (MDA), SOD (superoxide dismutase), and catalase (CAT) were assayed in serum, kidney, and lung tissues. Results: MDA decreased, but TTG and CAT increased in serum by the administration of CONPs at 15 mg/kg. In kidney homogenate obtained from the group treated with CONPs at 15 mg/kg, TAC, TTG, and CAT significantly increased compared to the control group. However, CONPs at 15, 30, and 60 mg/kg significantly decreased MDA level compared to the control group. In lung tissue, CONPs in doses of 15, 30 and 60 mg/kg significantly decreased CAT activity, TTG and TAC compared to the control group, while in kidney tissue, CONPs at the concentrations of 30 and 60 mg/kg significantly increased MDA compared to the control group. Conclusion: Our findings suggest that CONPs attenuate OS in the kidney and affect the serum levels of OS-related markers but induce OS in the lung tissue in a dose-dependent manner.