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Associations of propylene oxide exposure with fasting plasma glucose and diabetes: Roles of oxidative DNA damage and lipid peroxidation
2022
Liu, Wei | Wang, Bin | Yang, Shijie | Xu, Tao | Yu, Linling | Wang, Xing | Cheng, Man | Zhou, Min | Chen, Weihong
Whether propylene oxide (PO) exposure is associated with hyperglycemia were rarely explored. We aimed to determine the relationship between PO exposure and glucose metabolism, and potential role of oxidative stress. Among 3294 Chinese urban adults, urinary PO metabolite (N-Acetyl-S-(2-hydroxypropyl)-L-cysteine, 2HPMA), biomarkers of oxidative DNA damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) and lipid peroxidation (8-isoprostane, 8-iso-PGF₂α) in urine were determined. The associations of 2HPMA with 8-OHdG, 8-iso-PGF₂α, fasting plasma glucose (FPG), and risk of diabetes were explored. The roles of 8-OHdG and 8-iso-PGF₂α on association of 2HPMA with FPG and risk of diabetes were detected. After adjusted for potential confounders, each 1-unit increase in log-transformed concentration of 2HPMA was associated with a 0.15-mmol/L increase in FPG level, and the adjusted OR (95% CI) of diabetes by the associations of log-transformed urinary 2HPMA concentrations was 1.47 (95% CI: 1.03–2.11). Combination effects of 2HPMA with 8-OHdG or 8-iso-PGF₂α on risk of diabetes were detected, and elevated 8-iso-PGF₂α significantly mediated 34.5% of the urinary 2HPMA-associated FPG elevation. PO exposure was positively associated with FPG levels and risk of diabetes. PO exposure combined with DNA oxidative damage or lipid peroxidation may increase the risk of diabetes, and lipid peroxidation may partially mediate the PO exposure-induced FPG elevation.
اظهر المزيد [+] اقل [-]Use of biomarkers to evaluate the ecological risk of xenobiotics associated with agriculture
2018
Lima, Liana Bezerra Dias de | Morais, Paula Benevides de | Andrade, Ricardo Lopes Tortorela de | Mattos, Luciana Vieira | Moron, Sandro Estevan
This research aimed to evaluate the ecological risk of xenobiotics associated with agricultural activities by determining metal contents and biomarker responses using tucunaré (Cichla sp.) as a bioindicator. The work was conducted in the southwest region of the state of Tocantins, in the cities of Lagoa da Confusão and Pium. Water samples and specimens of Cichla sp. were collected in the Javaés and Formoso Rivers at three collection points (A, B and C). The concentrations of Cd, Pb, Cu, Cr, Mn, Ni and Zn in water and fish were analyzed. In fish, genotoxic, biochemical (glucose serum levels, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) and histological (gills and liver) biomarkers were assessed. In the water, the Cr and Mn concentrations at the three collection points exceeded the values for Class 1 rivers. In the muscle, Cr was above the maximum limit allowed for human consumption at the three collection points, although the values at Points B and C were not significantly different from that at Point A (p > 0.05). At the three collection points, the micronucleus test revealed a low frequency of micronuclei. Significant hyperglycemia and a decrease in the AST activity of the fish collected at Point C was observed. In the gills, the most frequent alterations were at Stages I and II, which indicated mild to moderate damage, and epithelial detachment was the most frequent variation. In the liver tissue, the most frequently observed histological changes were at Stages I and II and included cytoplasmic vacuolization, nuclear hypertrophy, dilated sinusoids and bile stagnation. The integrated evaluation of these biomarkers indicated that fish collected from areas with intense agricultural activities presented adaptive responses that were likely caused by the availability and bioaccumulation of certain xenobiotics in the environment.
اظهر المزيد [+] اقل [-]Association of urinary metals levels with type 2 diabetes risk in coke oven workers
2016
Liu, Bing | Feng, Wei | Wang, Jing | Li, Yaru | Han, Xu | Hu, Hua | Kwok, Woon | Zhang, Xiaomin | He, Meian
Studies indicated that occupationally exposed to metals could result in oxidative damage and inflammation and increase cardiovascular diseases risk. However, epidemiological studies about the associations of metals exposure with diabetes risk among coke oven workers were limited.This study aims to investigate the potential associations of 23 metals levels with the risk of diabetes among coke oven workers.The analysis was conducted in a cross-sectional study including 1493 participants. Urinary metals and urinary polycyclic aromatic hydrocarbons (PAHs) metabolites levels were determined by inductively coupled plasma mass spectrometer and gas chromatograph-mass spectrometer respectively. Multivariate logistic regression was used to investigate the associations of urinary metal levels with diabetes risk with adjustment for potential confounding factors including gender, age, BMI, education, smoking, drinking, physical activity, hypertension, hyperlipidemia and urinary PAHs metabolites levels.Compared with the normoglycemia group, the levels of urinary copper, zinc, arsenic, selenium, molybdenum, and cadmium were significantly higher in the diabetes group (all p < 0.05). Participants with the highest tertile of urinary copper and zinc had 2.12 (95%CI: 1.12–4.01) and 5.43 (95%CI: 2.61–11.30) fold risk of diabetes. Similar results were found for hyperglycemia risk. Besides, participants with the highest tertile of manganese, barium, and lead had 1.65(1.22–2.23), 1.60(1.19–2.16) and 1.45(1.05–1.99) fold risk of hyperglycemia when compared with the lowest tertlie.The results indicated that the urinary copper and zinc levels were positively associated with the risk of diabetes and hyperglycemia among coke oven workers. Urinary manganese, barium and lead levels were also associated with increased risk of hyperglycemia independently of other traditional risk factors. These findings need further validation in prospective study with larger sample size.
اظهر المزيد [+] اقل [-]Activation of prophenoloxidase and hyperglycemia as indicators of microbial stress in the blue swimmer crab Portunus pelagicus
2020
Rajendran, Saravanan | Vasudevan, Sugumar
Portunus pelagicus is exposed to different kinds of microorganisms leading to high metabolic stress that affects its life. The present study evaluates the activity of Phenoloxidase (PO), which is an enzyme that is actively involved in the activation of the immune defense system and hyperglycemia in P. pelagicus challenged with Escherichia coli and Vibrio harveyi injections. The results revealed a major impact of microbial injection on PO activity and significant variations in hemolymph glucose and CHH levels. Reduction of glucose level was observed after 24 h microbial incubation (275.26 ± 28.85 and 175.23 ± 21.70 μg/ml in V. harveyi and E. coli injected crabs, respectively). An elevated level of CHH (13.54 ± 0.55 fmol/ml) was observed in V. harveyi-injected crabs, and increased PO activity was recorded in E. coli-injected crabs. The results of the present study indicate that microbial stress leads to the activation of the defense system and hyperglycemia in P. pelagicus.
اظهر المزيد [+] اقل [-]In vitro toxic interaction of arsenic and hyperglycemia in mitochondria: an important implication of increased vulnerability in pre-diabetics
2022
Kalo, Mersad Bagherpour | Rezaei, Mohsen
Environmental pollutants and lifestyle both contribute to the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide. Evidence suggests that exposure to environmental contaminants such as arsenic is associated with impaired glucose metabolism and insulin signaling. In the present study, isolated rat liver mitochondria (1 mg/ml) were co-exposed to low concentration of arsenic trioxide (ATO) (IC₂₅ = 40 µM) and hyperglycemic condition (20, 40, 80, 160 mM glucose or 20, 40, 80, 160 mM pyruvate (PYR)). Mitochondrial dehydrogenase activity (complex II), glutathione content (GSH), reactive oxygen species (ROS), lipid peroxidation, mitochondrial membrane potential (ΔΨ), and mitochondrial swelling were then evaluated in the presence of ATO 40 µM and PYR 40 mM. Unexpectedly, glucose alone (20, 40, 80, 160 mM) had no toxic effect on mitochondria, even at very high concentrations and even when combined with ATO. Interestingly, PYR at low concentrations (≤ 10 mM) has a protective effect on mitochondria, but at higher concentrations (≥ 40 mM) with ATO, it decreased the complex II activity and increased mitochondrial ROS production, lipid peroxidation, GSH depletion, mitochondrial membrane damage, and swelling (p < 0.05). In conclusion, PYR but not glucose increased ATO mitochondrial toxicity even at low concentrations. These results suggest that pre-diabetics with non-clinical hyperglycemia, who are inevitably exposed to low concentrations of arsenic through food and water, may develop mitochondrial dysfunction that accelerates their progression to diabetes over time.
اظهر المزيد [+] اقل [-]Cyperus iria aqueous-ethanol extract ameliorated hyperglycemia, oxidative stress, and regulated inflammatory cytokines in streptozotocin-induced diabetic rats
2022
Saeed, Myeda | Sharīf, ʻAlī | Hassan, Saeed Ul | Akhtar, Bushra | Muhammad, Faqir | Malik, Maryam
Type 2 diabetes mellitus is a complicated metabolic disorder with no definite treatment. Cyperus iria (Cyperaceae) possess several traditional therapeutic uses. According to the folklore tales, the whole plant of Cyperus iria possesses antihyperglycemic activity. The present study was undertaken to investigate whether aqueous-ethanol extract of Cyperus iria can ameliorate the altered activities of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats along with appraisal of inflammatory and stress markers involved in endocrine dysfunction. Presence of biophenolics and flavonoids might be responsible for the antidiabetic potential. STZ-induced diabetic rats were treated orally with Cyperus iria extract (125, 250, and 500 mg/kg) for 15 days. Blood samples were collected. Metformin was used as positive control. Significantly higher quantities of phenolic (82.79±0.003 mg/g GAE) and flavonoid (13.61±0.002 mg/g QE) contents were present. Inhibitory concentration (IC50) exhibited an excellent potential for both antioxidant (IC50= 3.22 μg/mL) and alpha amylase (IC50=36.29 μg/mL) inhibitory assays. High-performance liquid chromatography (HPLC) confirmed the existence of myercetin, quercetin, kaempferol, and ferulic acid. Cyperus iria aqueous-ethanol extract exhibits good tolerance against glucose at 90 min in normal rats. Streptozotocin-induced hyperglycemia declined significantly at day 9 (265 mg/dL) along with improvement in inflammatory (TNF-α=15.6± 0.2 g/l, COX-2=357±0.396 U/l, IL-6= 572±0.99 pg/l) and oxidative stress markers (SOD= 163±0.616 and GSH-ST= 95.8±0.44 U/mL) along with biochemical parameters in a dose-dependent manner. Present study suggests that Cyperus iria aqueous-ethanol extract possesses hypoglycemic potential which might be attributed to the decrease in oxidative stress and inflammatory markers.
اظهر المزيد [+] اقل [-]Protective effects of Artemisia judaica extract compared to metformin against hepatorenal injury in high-fat diet/streptozotocine-induced diabetic rats
2020
Albasher, Gadah | Alwahaibi, Mona | Abdel-Daim, Mohamed M. | Alkahtani, Saad | Almeer, Rafa
Diabetes mellitus (DM) is one of the most dangerous incurable diseases that affects a large number of people worldwide. Artemisia species have various protective activities and are widely used for the control of diabetes in folkloric medicine. Therefore, the current study was designed to illustrate the protective effect of oral administration of Artemisia judaica extract (AjE) against hepatorenal damage in a high-fat diet/streptozotocin (HFD/STZ) rat model of hyperlipidemia and hyperglycemia. Animals were divided into five groups—control, AjE, HFD/STZ, HFD/STZ-AjE (300 mg/kg), and HFD/STZ-MET (100 mg/kg)—and treated daily for 28 days. The results revealed that STZ-injected rats showed marked hyperglycemia and hypoinsulinemia in addition to high levels of cholesterol, triglycerides, and low- and high-density lipoproteins compared to control rats. Significant elevations in hepatic (AST and ALT) and renal (urea, uric acid, and creatinine) function markers were observed in the serum of diabetic rats. Additionally, STZ injection caused remarkable elevations in lipid peroxidation and nitric oxide levels as well as suppression of antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione). Marked elevations in TNF-α and Bax levels with a decline in Bcl-2 levels were detected after STZ injection. Furthermore, TGF-β1 expression levels were significantly upregulated in the liver and kidney tissues. Rats that received AjE or MET showed significant improvement in most of the aforementioned parameters, and the protective efficacy was higher for AjE than for MET. Histopathological screening confirmed the biochemical findings. Conclusively, our results illustrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and antiapoptotic activities of AjE against hepatorenal injury in HFD/STZ-induced diabetes.
اظهر المزيد [+] اقل [-]Electrocardiographic and histopathological characterizations of diabetic cardiomyopathy in rats
2022
Diabetes is a clinical condition that is associated with insulin deficiency and hyperglycemia. Cardiomyopathy, retinopathy, neuropathy, and nephropathy are well known complications of the elevated blood glucose. Diabetic cardiomyopathy is a clinical disorder that is associated with systolic and diastolic dysfunction along with cardiac fibrosis, inflammation, and elevated oxidative stress. In this study, diabetes was induced by intraperitoneal injection of streptozotocin (STZ) 50 mg/kg. We determined the plasma levels of cardiac troponin-T (cTnT) and creatinine kinase MB (CK-MB) by ELISA. Diabetic rats showed abnormal cardiac architecture and increased collagen production. Significant elevation in ST-segment, prolonged QRS, and QT-intervals and increased ventricular rate were detected. Additionally, diabetic rats showed a prolongation in P wave duration and atrial tachyarrhythmia was observed. Plasma levels of cTnT and CK-MB were elevated. In conclusion, these electrocardiographic changes (elevated ST-segment, prolonged QT interval, and QRS complex, and increased heart rate) along with histopathological changes and increased collagen formation could be markers for the development of diabetic cardiomyopathy in rats.
اظهر المزيد [+] اقل [-]Sublethal Effects of Biogenic Silver Nanoparticles and Silver Nitrate in the Neotropical Fish Prochilodus lineatus: Is the Nanoform Really Less Toxic?
2022
Ferroni, Hellen Ingrid | Bezerra, Vanessa | Risso, Wagner Ezequiel | Martinez, Claudia Bueno dos Reis | Simonato, Juliana Delatim
Biogenic silver nanoparticles (bNAg) have been suggested as a less toxic alternative to ionic silver (Ag), and also a more ecological alternative to synthetic silver nanoparticles (sNAg). However, the differences between the sublethal effects caused by bNAg and silver nitrate (AgNO₃) are hardly known, especially in native fishes of the Neotropical region. Most researchers have only compared the effects of sNAg and AgNO₃. Thus, the objective of this work was to evaluate the effects of bNAg, produced by the fungus Fusarium oxysporum, and to compare these with the effects of AgNO₃ in the Neotropical fish Prochilodus lineatus. The animals were exposed for 24 and 96 h at nominal concentrations of 10 and 25 µg L⁻¹ of Ag. At the end of the exposures, Ag accumulation, metallothionein concentration, hematological parameters, plasma glucose and ion concentrations, activity of the main ATPases and carbonic anhydrase in the gills, enzymatic and non-enzymatic antioxidants, lipid peroxidation, and neurotoxic effects were evaluated. Both bNAg and AgNO₃ caused Ag accumulation in the blood, gills, and brain, in addition to neurotoxic effects on muscle, alterations in reduced glutathione concentration in the gills, and increased glutathione-S-transferase activity in the liver. Hyperglycemia, ionic imbalances, and alterations in the activity of ion transport enzymes in the gills were also observed. As the effects of bNAg were similar to the effects of AgNO₃, it is concluded that animals exposed to the highest concentration of silver were the most affected, regardless of the form of silver used in the exposure medium.
اظهر المزيد [+] اقل [-]Acacia jacquemontii ethyl acetate extract reduces hyperglycemia and pro-inflammatory markers while increasing endogenous antioxidant potential in alloxan-induced diabetic rats
2022
Awan, Ambreen Mehmood | Majeed, Wafa | Muhammad, Faqir | Faisal, Muhammad Naeem
Acacia jacquemontii possess has numerous traditional therapeutic uses. The rationale of this study was to investigate the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in the downregulation of hyperglycemia. The current study was performed in two parts, in vitro, through characterization (high-performance liquid chromatography), estimation of total phenolic content, total flavonoid content, antioxidant (2,2-diphenyl-1-picrylhydrazylassay), and α-amylase inhibitory activities of the studied extract, and in vivo using Wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250 mg/kg, and AJEAE 500 mg/kg. The effects of AJEAE on fasting plasma glucose, plasma insulin, HOMA-IR, oral glucose tolerance test, glycated hemoglobin (HBA1c), lipid profile, inflammatory cytokines (Interleukin-6, tumor necrosis factor-alpha), and oxidative stress markers (lipid peroxidation, nitic oxide, superoxide dismutase, catalase, glutathione peroxidase) were evaluated. Our findings confirmed the presence of quercetin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinnamic acid, and ferulic acid in AJEAE. Total flavonoid and phenolic contents in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g, respectively. Significant inhibition of DPPH (69.470%/1 mg/ml) and α-amylase (71.8%/1 mg/ml) activities were exhibited by AJEAE. Alloxan-injected rats showed marked hyperglycemia and hypoinsulinemia, and increased inflammatory marker levels as compared to normal control (p < 0.001). Additionally, raised levels of triglyceride (139.7 ± 2.771), total cholesterol (198.7 ± 1.856), very low-density lipoprotein (33.43 ± 0.2728), low-density lipoprotein (155.5 ± 2.754), lipid peroxidation, and nitric oxide (p < 0.001) and decreased levels of high-density lipoprotein (17.20 ± 0.1732), superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic rats (p < 0.001). AJEAE significantly (p < 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic β cells. Conclusively, our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and pancreatic beta β cell regenerative properties of AJEAE against alloxan-induced diabetes.
اظهر المزيد [+] اقل [-]