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Pre-differentiation exposure of PFOA induced persistent changes in DNA methylation and mitochondrial morphology in human dopaminergic-like neurons
2022
Zhao, Han | Xie, Junkai | Wu, Shichen | Sánchez, Oscar F | Zhang, Xinle | Freeman, Jennifer L. | Yuan, Chongli
Perfluorooctanoic acid (PFOA) is abundant in environment due to its historical uses in consumer products and industrial applications. Exposure to low doses of PFOA has been associated with various disease risks, including neurological disorders. The underlying mechanism, however, remains poorly understood. In this study, we examined the effects of low dose PFOA exposure at 0.4 and 4 μg/L on the morphology, epigenome, mitochondrion, and neuronal markers of dopaminergic (DA)-like SH-SY5Y cells. We observed persistent decreases in H3K4me3, H3K27me3 and 5 mC markers in nucleus along with alterations in nuclear size and chromatin compaction percentage in DA-like neurons differentiated from SH-SY5Y cells exposed to 0.4 and 4 μg/L PFOA. Among the selected epigenetic features, DNA methylation pattern can be used to distinguish between PFOA-exposed and naïve populations, suggesting the involvement of epigenetic regulation. Moreover, DA-like neurons with pre-differentiation PFOA exposure exhibit altered network connectivity, mitochondrial volume, and TH expression, implying impairment in DA neuron functionality. Collectively, our results revealed the prolonged effects of developmental PFOA exposure on the fitness of DA-like neurons and identified epigenome and mitochondrion as potential targets for bearing long-lasting changes contributing to increased risks of neurological diseases later in life.
Mostrar más [+] Menos [-]Supplementation with selenium nanoparticles alleviates diabetic nephropathy during pregnancy in the diabetic female rats
2022
Alhazza, Ibrahim M. | Ebaid, Hossam | Omar, Mohamed S. | Hassan, Iftekhar | Habila, Mohamed A. | Al-Tamimi, Jameel | Sheikh, Mohamed
The bioactivity of nanoparticles has engendered a promise in scientific communities for developing novel therapeutic strategies. This study investigated the protective effects of selenium nanoparticles (SeNPs) against kidney injury in streptozocin-induced diabetes during pregnant (DDP) rats. The female rats were separated into three groups (n = 8). Group 1 received the vehicle, normal saline. Group 2 received a single intraperitoneal dose of 50 mg/kg of streptozocin. Group 3 received a single intraperitoneal injection of 50 mg/kg of streptozocin, followed by treatment with SeNPs at a dose of 2.5 mg/kg twice a week for 6 weeks (1 week before gestation and continuing for 5 additional weeks). The structure formed by the fabricated SeNPs with citric acid in the presence of ascorbic acid indicated that nano-Se was associated with a carbon matrix. The diabetic group suffered from polyuria, a reduction in body weight, delayed gestation, and only 40% successful pregnancy compared with the control rats. Interestingly, SeNPs significantly reduced the rate of urination, accelerated the start of gestation, and increased the percentage of successful pregnancy in females with DM. Severe changes were observed in the pancreatic β-cells of the diabetic rats, with darkly stained and fragmented chromatin in nuclei, while SeNPs partially restored the normal morphological features of the pancreatic β-cells. The concentrations of urea, creatinine, MDA, and glucose were significantly increased in the diabetic rats, while GSH was significantly reduced compared with controls. Interestingly, SeNPs restored all of these parameters to values at or near control levels. SeNPs were capable of improving the histological structure of the kidney in mothers with DDP. Hence, the present work is relevant to GDM demonstrating SeNPs shielding the kidney structure and function in vivo.
Mostrar más [+] Menos [-]The effectiveness of vitamin C on quinalphos ileal toxicity: a study of histological, ultrastructural, and oxidative stress markers
2022
Zaki, Mohamed Samir Ahmed | El-kott, Attalla F. | AlGwaiz, Hussah I. M. | Sideeg, Abulqasim M. | Andarawi, Mohamed | Eid, Refaat A.
There is a significant hazard of human exposure to the organophosphates which is a constant threat, and they are responsible for numerous cases of poisoning and mammalian toxicity annually in non-target wildlife. The antioxidants, including the vitamin C (Vit C), have a protective effect on some organophosphorus compounds-induced organ damage. Quinalphos (QP) is one of these compounds. The investigation’s objective is to see if there was any effect of QP on the rat ileum which could be rectified by using Vit C. Three groups of 24 animals were created. As a control, the first group was given pure water. Second group subjected to oral gavages of QPs. Third group rats were given oral gavages of Vit C plus QPs for 10 days. The reaction of ileal enterocytes to food-borne QPs was marked by poorly organized microvilli, numerous vacuoles within them, disrupted nuclei with chromatin margination, disoriented mitochondria, and an expanded intercellular space. The absorptive columnar cell illustrated many vacuoles inside with herniation of microvilli, and normal goblet cells were also seen. Many Paneth cells towards the lumen of intestinal gland contained secretory granules of different sizes and shapes. The histological architecture of the ileal mucosa in the QP plus Vit C group was found to be close to those of healthy controls. The outcomes of this study suggest that administering Vit C in rats treated with QPs protects them from ill dysfunction caused by QP.
Mostrar más [+] Menos [-]Protective role of green tea against paraquat toxicity in Allium cepa L.: physiological, cytogenetic, biochemical, and anatomical assessment
2022
Yirmibeş, Ferhat | Yalçin, Emine | Çavuşoğlu, Kültiğin
In this study, the toxic effects of paraquat, one of the most commercially sold herbicides in the world, and the protective role of green tea leaf extract (GTLE) against these effects were investigated. Allium cepa L. bulbs (n = 16) were used as test material. One hundred milligrams per liter dose of paraquat and 190 and 380 mg/L doses of GTLE were preferred. Paraquat toxicity was investigated with the help of physiological (percent germination, root length, and weight gain), cytogenetic (mitotic index = MI, micronucleus = MN, and chromosomal damages = CAs), biochemical (superoxide dismutase = SOD, catalase = CAT, malondialdehyde = MDA), and anatomical (meristematic cell damages) parameters. A. cepa bulbs were divided into 6 groups as 1 control and 5 applications. The control group was germinated with tap water, and the application groups were germinated with paraquat and two different doses of GTLE. Germination was carried out at room temperature for 72 h. At the end of the period, A. cepa bulbs were prepared for physiological, cytogenetic, biochemical, and anatomical analyzes using routine preparation techniques. As a result, paraquat application caused a decrease in physiological parameters and an increase in cytogenetic (except MI) and biochemical parameters. Compared to the control (group I), the germination percentage decreased by 38%, root length 12.5 times, and weight gain 5 times decreased in group IV treated with paraquat. MDA level increased 2.58 times, SOD activity 2.48 times, and CAT activity 4.51 times increased. Paraquat application caused a decrease in the percentage of MI and an increase in the number of MN and CAs. Paraquat application caused CAs in the form of fragment, sticky chromosome, unequal distribution of chromatin, bridge, nucleus with vacuoles, nucleus bud, and reverse polarization. In the meristematic cells of the root tips applied paraquat, unclearly vascular tissue, flattened cell nucleus, epidermis, and cortex cell deformation were observed. The application of GTLE together with paraquat caused an increase in the physiological parameter values and a decrease in the cytogenetic (except MI) and biochemical parameter values. An improvement in the severity of damages induced by paraquat was also observed in root tip meristematic cells. It was determined that the improvements observed in all these parameters were related to the dose of GTLE applied. The 380 mg/L dose of GTLE provided more protection than the 190 mg/L dose. Compared to group IV in which paraquat was applied, the germination percentage increased by 21%, root length 5.83 times, and weight gain 2.92 times increased in group VI administered 380 mg/L dose of GTLE. In addition, MDA level decreased 1.78 times, SOD activity 1.59 times and CAT activity 1.65 times. In conclusion, paraquat administration at a dose of 100 mg/L caused physiological, cytogenetic, biochemical, and anatomical toxicity in A. cepa bulbs. GTLE application, on the other hand, resulted in improvements in the severity of this toxicity induced by paraquat, depending on the dose. Therefore, GTLE can be used as an effective nutritional supplement to reduce or prevent the toxicity caused by environmental agents such as pesticides.
Mostrar más [+] Menos [-]Cigarette heavy smoking alters DNA methylation patterns and gene transcription levels in humans spermatozoa
2022
Laqqan, Mohammed M. | Yassin, Maged M.
Tobacco smoking is considered the most common reason of death and infertility around the world. This study was designed to assess the impact of tobacco heavy smoking on sperm DNA methylation patterns and to determine whether the transcription level of ALDH3B2, PTGIR, PRICKLE2, and ALS2CR12 genes is different in heavy smokers compared to non-smokers. As a screening study, the 450 K array was used to assess the alteration in DNA methylation patterns between heavy smokers (n = 15) and non-smokers (n = 15). Then, four CpGs that have the highest difference in methylation level (cg16338278, cg08408433, cg05799088, and cg07227024) were selected for validation using deep bisulfite sequencing in an independent cohort of heavy smokers (n = 200) and non-smokers (n = 100). A significant variation was found between heavy smokers and non-smokers in the methylation level at all CpGs within the PRICKLE2 and ALS2CR12 gene amplicon (P < 0.001). Similarly, a significant variation was found in the methylation level at nine out of thirteen CpGs within the ALDH3B2 gene amplicon (P < 0.01). Additionally, eighteen CpGs out of the twenty-six within the PTGIR gene amplicon have a significant difference in the methylation level between heavy smokers and non-smokers (P < 0.01). The study showed a significant difference in sperm global DNA methylation, chromatin non-condensation, and DNA fragmentation (P < 0.001) between heavy smokers and non-smokers. A significant decline was shown in the transcription level of ALDH3B2, PTGIR, PRICKLE2, and ALS2CR12 genes (P < 0.001) in heavy smokers. In conclusion, heavy smoking influences DNA methylation at several CpGs, sperm global DNA methylation, and transcription level of the PRICKLE2, ALS2CR12, ALDH3B2, and PTGIR genes, which affects negatively the semen parameters of heavy smokers.
Mostrar más [+] Menos [-]Cadmium-induced ultrastructural changes and apoptosis in the gill of freshwater mussel Anodonta woodiana
2022
Li, Yong Quan | Chen, Chien M. | Liu, Na | Wang, Lan
This study investigated the acute toxicity of cadmium (Cd) to the freshwater mussel Anodonta woodiana. The freshwater mussels were exposed to five concentrations of Cd (0 mg/L, 8.43 mg/L, 16.86 mg/L, 33.72 mg/L, and 67.45 mg/L) for up to 96 h. The 24-h, 48-h, 72-h, and 96-h LC₅₀ values for Cd were estimated as 562.3 mg/L, 331.1 mg/L, 182.0 mg/L, and 134.9 mg/L, respectively. Caspase-3, caspase-8, caspase-9, and Ca-ATPase activities; protein and H₂O₂ levels; DNA fragmentation; and ultrastructure of the gill were also investigated. The activities of caspase-3 and caspase-9 in mussels were increased by Cd in a dose-dependent manner, where higher doses of Cd (33.72 mg/L and 67.45 mg/L) significantly increased the enzyme activities compared to the controls (P < 0.05). The caspase-8 activity was significantly depressed by a low dose of Cd (8.43 mg/L) but was clearly induced by higher doses of Cd (16.86 mg/L, 33.72 mg/L, and 67.45 mg/L) (P < 0.05). The Ca-ATPase activity and H₂O₂ levels were elevated and reached maximum values under the medium dose of Cd (16.86 mg/L). However, protein levels were decreased by Cd in an inverse dose–dependent manner. In the gills of the mussels, Cd treatment induced DNA fragmentation as demonstrated by DNA ladders observed via agarose gel electrophoresis. Moreover, ultrastructural alterations in gill cells of mussels treated with Cd (16.86 mg/L and 67.45 mg/L) for 96 h were observed by electronic microscopy. The ultrastructure abnormalities were characterized by the following features: (1) a disordered arrangement and breaking off of microvilli of epithelial cells; (2) chromatin condensed near the nuclear membrane and the appearances of extremely irregular nuclei, some with a fingerlike shape and an unclear, swollen, invaginated, or ruptured nuclear membrane and apoptotic bodies; (3) swollen and vacuolating mitochondria, some with disintegrated or missing cristae; (4) a disintegrated rough endoplasmic reticulum containing different sizes of vesicles; and (5) shrinking and deformation of Golgi bodies with decreased vesicle numbers. Our results demonstrated that Cd could activate caspase-3, caspase-8, caspase-9, and Ca-ATPase; cause ultrastructural changes; and produce DNA fragmentation in the mussels investigated. Based on the information obtained through this study, it is reasonable to conclude that Cd can induce apoptosis in the gills of the mussels, eventually leading to tissue damage.
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