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Chronic pesticide exposure induced aberrant Notch signalling along the visual pathway in a murine model النص الكامل
2021
Sanyal, Shalini | Law, Sujata
Pesticides aid in crop-protection against pests and increase yield. However, the xenobiotic stress exerted by pesticides leads to the deterioration of human and animal health. There is a lacuna in our knowledge about their impact on the ocular surface The present work sheds light on this gap by analysing the deterioration of visual acuity as a consequence of pesticide induced xenobiotic stress and Notch pathway dysregulation.Alteration in the expression of vital components of the notch signalling was analyzed along the visual pathway with special focus on its two terminals-the cornea and the visual cortex, by mimicking the on-field scenario regarding chronic pesticide exposure in experimental murine model (Swiss albino mice; Mus musculus). Various aspects were taken into consideration through visual acuity tests, histological evaluations, culture analyses, wound healing assays, flowcytometric evaluation, fluorescence microscopic studies etc. Complete dysregulation of key players of the Notch signalling pathway was observed in both: cells of the ocular surface as well as those in the murine visual cortex post pesticide exposure, indicating activities relating to cell proliferation, differentiation and wound healing in the pesticide exposed samples. Ultra-microscopic analyses corroborated our findings by revealing the loss of fine neural processes in the visual cortex of the pesticide exposed murine samples, thereby hinting at delayed perception to visual stimuli. In vivo evaluations of the functional capacity of the neuroanatomical structures along the visual pathway also confirmed that pesticide exposure leads to severe damage along the various parts of the visual pathway, right from the ocular surface to the visual cortex.
اظهر المزيد [+] اقل [-]Oil induces chlorophyll deficient propagules in mangroves النص الكامل
2020
Veldkornet, Dimitri | Rajkaran, Anusha | Paul, Swapan | Naidoo, Gonasageran
In Australia, some trees of the mangrove, Avicennia marina, growing in a chronic oil polluted site, produce chlorophyll deficient (albino) propagules. We tested the hypothesis that albinism was due to an oil-induced mutant allele that controls photosynthesis. We determined whether there are genetic differences between normal and chlorophyll deficient propagules. Four gene regions (nuclear 18S–26S cistron; chloroplast - trnH-psbA, rsp16 and matK) were sequenced and analysed for normal and albino propagules. Mutations occurred in both nuclear (ITS) and coding chloroplast (matK) genes of albino propagules. There were 10 mutational differences between normal and albino propagules in the matK samples. Analysis of molecular variation (AMOVA) of the matK dataset indicated highly significant genetic differentiation between normal and albino propagules. Our study suggests for the first time that PAHs from a chronic oil polluted site resulted in mutations in both nuclear and chloroplast genes, resulting in the production of albino propagules.
اظهر المزيد [+] اقل [-]Generation of albino via SLC45a2 gene targeting by CRISPR/Cas9 in the marine medaka Oryzias melastigma النص الكامل
2020
Jeong, Chang-Bum | Kang, Hye-Min | Hong, Sung-Ah | Byeon, Eunjin | Lee, Jin-Sol | Lee, Young-Hwan | Choi, Ik-Young | Bae, Sangsu | Lee, Jae-seong
To produce albinism in the marine medaka Oryzias melastigma, we disrupted the solute carrier family 45 (SLC45a2) gene by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 with a single guide RNA (sgRNA). Selected sgRNAs were able to target a SLC45a2 gene as confirmed by genotyping and heteroduplex mobility assay (HMA). Of the survived embryos after injection, 54.2% and 60.0% embryos exhibited albinism phenotype by sgRNA1 and sgRNA2, respectively. Deep sequencing at the on-target sites showed different insertion and deletion (indel) mutation profiles near the DNA cleavage sites, indicating high efficacy of producing SLC45a2 knock-out mutants by this method. Moreover, HMA at the potential off-target sites revealed that off-target activity would be induced at a low rate, or not induced at all. This albino marine medaka will be a good model for marine molecular ecotoxicology in establishment of diverse in vivo endpoints, and the application of this efficient gene targeting method in the marine medaka would be useful tool for mechanistic approaches.
اظهر المزيد [+] اقل [-]Wound healing properties of green (using Lawsonia inermis leaf extract) and chemically synthesized ZnO nanoparticles in albino rats النص الكامل
2022
Metwally, Asmaa A. | Abdel-Hady, Abdel-Nasser A. A. | Haridy, Mohie A. M. | Ebnalwaled, Khaled | Saied, AbdulRahman A. | Soliman, Ahmed S.
Wound healing is one of the utmost medical issues in human and veterinary medicine, which explains the urgent need for developing new agents that possess wound healing activities. The present study aimed to assess the effectiveness of green and chemical zinc oxide nanoparticles (ZnO-NPs) for wound healing. ZnO-NPs (green using Lawsonia inermis leaf extract and chemical) were synthesized and characterized by X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and high-resolution transmission electron microscopy (HRTEM). The gels containing the nanomaterials were prepared and inspected. Forty-five albino rats were divided into three groups, the control group was treated with normal saline 0.9%, and the other two groups were treated with gels containing green or chemical ZnO-NPs, respectively. On the 3ʳᵈ, 7ᵗʰ, 14ᵗʰ, and 21ˢᵗ days post-treatment (PT), the wounds were clinicopathologically examined. Both nanomaterials have good crystallinity and high purity, but green ZnO-NPs have a longer nanowire length and diameter than chemical ZnO-NPs. The formed gels were highly viscous with a pH of 6.5 to 7. The treated groups with ZnO-NP gels showed clinical improvement, as decreased wound surface area (WSA) percent (WSA%), increased wound contraction percent (WC%), and reduced healing time (p < 0.05) when compared with the control group. The histological scoring showed that the epithelialization score was significantly higher at the 21ˢᵗ day post-treatment in the treated groups than in the control group (p < 0.05), but the vasculature, necrosis, connective tissue formation, and collagen synthesis scores were mostly similar. The green and chemical ZnO-NP gels showed promising wound healing properties; however, the L. inermis–mediated ZnO-NPs were more effective.
اظهر المزيد [+] اقل [-]Effect of gervital in attenuating hepatotoxicity caused by methotrexate or azathioprine in adult albino rats النص الكامل
2022
Abdul-Hamid, Manal | Abdel-Reheim, Eman Salah | Hegazy, Walaa | Allam, Ahmed | Othman, Sarah I. | Alwaele, Maha Abdulla | Abdel-Kawi, Samraa Hussein
Methotrexate (MTX) and azathioprine (AZA) are chemotherapeutic, antimetabolic, and immunosuppressive agents with substantial risks such as oxidative lesions to the liver. This study examined the effect of grape seed extract (GSE; gervital) in attenuating hepatotoxicity caused by MTX or AZA treatment. Rats were divided into six groups (six rats per group): Group I, normal control group; Group II, GSE (150 mg/kg/day); Group III, MTX (8 mg/kg/week); Group IV, AZA (15 mg/kg/day); Group V, GSE (150 mg/kg/day) + MTX (8 mg/kg/week); and Group VI, GSE (150 mg/kg/day) + AZA (15 mg/kg/day). After 35-day experimental period, all rats were sacrificed and blood was collected for biochemical study and hemoglobin (Hb) assessment. The liver was weighed and triaged for histological, ultrastructural, and biochemical studies. MTX and AZA treatment decreased Hb levels, increased relative liver weight, increased the activity of glutamate pyruvate transaminase (ALT) and glutamate oxaloacetate transaminase (AST) aminotransferase (ALT) and aspartate aminotransferase (AST) values, and displayed histopathological and ultrastructural alterations. These changes included the disorganization of hepatocytes, pyknosis, karyolysis of some nuclei, and mononuclear leukocytic infiltration. The liver with significant oxidative stress (OS) showed decreased reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and increased malondialdehyde (MDA) levels. In contrast, GSE administration ameliorated ALT, AST, and all histopathological and ultrastructural changes. GSE treatment also reduced MDA levels but increased the antioxidant parameters. In conclusion, it was concluded that GSE supplementation could be considered as a promising antioxidant in reducing OS, histopathological and ultrastructural alterations induced by MTX and AZA.
اظهر المزيد [+] اقل [-]Toxicological assessment of low-dose bisphenol A, lead and endosulfan combination: chronic toxicity study in male rats النص الكامل
2022
Dökmeci, Ayşe Handan | Karaboğa, İhsan | Güzel, Savaş | Erboğa, Zeynep Fidanol | Yılmaz, Ahsen
In the present study, toxic effects, both alone and combined, of bisphenol A (BPA), lead (Pb) and endosulfan (ES) in the low doses were investigated in rat liver and kidney functions. In the study, bisphenol A (BPA), lead (Pb) and endosulfan (ES) were chosen because although they are the chemicals people are most frequently exposed to, no combined toxic effect studies were conducted with these chemicals. Sixty-four male Wistar albino rats were used in the study, and they were randomly divided into eight groups (n = 8 per group); control, BPA (5 mg/kg), Pb (100 ppm), ES (0.61 mg/kg), BPA+Pb, BPA+ES, Pb+ES and BPA+P+ES. The rats were sacrificed after 65 days of treatment. Severe histopathological changes in the liver and kidney tissues were observed in the rats exposed to BPA+Pb+ES combination. Elevated malondialdehyde (MDA) in the liver and decreased superoxide dismutase activity (SOD) in the kidney tissue were detected in the BPA+Pb+ES group compared to those of the control group. It was found that serum alanine aminotransferase (ALT) and blood urea nitrogen (BUN) and creatinine (CREA) levels were higher in the BPA+Pb+ES combination group than the control group. Also, combined exposure of BPA, Pb and ES caused apoptotic cell numbers and inducible nitric oxide (iNOS) to increase in the liver and kidney tissues. The results of the present study suggested that the BPA, Pb and ES caused more dramatic changes to both histological architecture and cell apoptosis in the liver and kidney tissues when there was a combined exposure.
اظهر المزيد [+] اقل [-]Histopathological, Immunohistochemical, And Molecular Alterations In Brain Tissue And Submandibular Salivary Gland Of Atrazine-Induced Toxicity In Male Rats النص الكامل
2022
Ahmed, Yasmine H. | AbuBakr, Huda O. | Ahmad, Ismail M. | Ahmed, Zainab Sabry Othman
Atrazine (ATZ) is herbicide that has been widely used for different crops. This extensive use has resulted in severe deleterious effects in different species. In this work, we investigated the potentially harmful effect of atrazine herbicide on the brain and submandibular salivary gland. Our investigation was carried out on 20 adult male albino rats that were equally divided into two groups. The first group received distilled water as control, while the second group received ATZ at 200 mg/kg body weight/ day via stomach gavage for 30 successive days of the experiment; the oral LD50 for ATZ is 3090 mg/kg. Our findings revealed the ability of ATZ to cause damage to the cerebrum, hippocampus, and submandibular salivary gland. This damage resulted from the induced oxidative stress, which was indicated by a significant elevation in malondialdehyde (MDA) concentration, DNA fragmentation, tumor necrotic factor-alpha (TNF-α) expression, with a significant decrease in reduced glutathione (GSH) level and reduction of B cell lymphoma 2 (BCL2), dopamine receptor D1 (Drd1), cAMP-responsive element-binding protein 1 (Creb1) genes expression after ATZ exposure. Moreover, degeneration of cells, cytoplasmic vacuolation, congestion of blood vessels, a strong immune reaction to caspase 3, and negligible immune expression of a glial fibrillary acidic protein (GFAP) were also noticed in the ATZ-treated group. We concluded that ATZ induces oxidative stress and has a toxic and apoptotic effects on the cerebrum, hippocampus, and salivary gland of adult male albino rats.
اظهر المزيد [+] اقل [-]Lead Nitrate Induces Inflammation and Apoptosis in Rat Lungs Through the Activation of NF-κB and AhR Signaling Pathways [Erratum: September 2022, v.29(43), p.64971] النص الكامل
2022
Attafi, Ibraheem M. | Bakheet, Saleh A. | Ahmad, Sheikh F. | Belali, Osamah M. | Alanazi, Fawaz E. | Aljarboa, Suliman A. | AL-Alallah, Ibrahim A. | Korashy, Hesham M.
Lead (Pb) is one of the most frequent hazardous air contaminants, where the lungs are particularly vulnerable to its toxicity. However, the Pb distribution and its impact on lung inflammation/apoptosis and particularly the involvement of nuclear factor kappa B (NF-κB) and aryl hydrocarbon receptor (AhR) signaling pathways in Pb-induced lung toxicity have not yet been fully investigated. Adult male Wistar albino rats were exposed to Pb nitrate 25, 50, and 100 mg/kg b.w. orally for 3 days. The histopathological changes of several rat organs were analyzed using hematoxylin and eosin staining. The concentrations of Pb ion in different organ tissues were quantified using inductive coupled plasma mass spectrometry, while gas chromatography-mass spectrometry was used to identify organic compounds. The changes in the mRNA and protein expression levels of inflammatory and apoptotic genes in response to Pb exposure were quantified by using RT-PCR and Western blot analyses, respectively. Treatment of rats with Pb for three consecutive days significantly increased the accumulation of Pb in lung tissues causing severe interstitial inflammation. Pb treatment also increased the percentage of lung apoptotic cells and modulated apoptotic genes (Bc2, p53, and TGF-α), inflammatory markers (IL-4, IL-10, TNF-α), and oxidative stress biomarkers (iNOS, CYP1A1, EphX) in rat lung tissues. These effects were associated with a significant increase in organic compounds, such as 3-nitrotyrosine and myeloperoxidase, and some inorganic elements, such as selenium. Importantly, the Pb-induced lung inflammation and apoptosis were associated with a proportional increase in the expression of NF-κB and AhR mRNAs and proteins. These findings clearly show that Pb induces severe inflammation and apoptosis in rat lungs and suggest that NF-κB and AhR may play a role in Pb-induced lung toxicity.
اظهر المزيد [+] اقل [-]Comparative assessment on the probable mechanisms underlying the hepatorenal toxicity of commercial imidacloprid and hexaflumuron formulations in rats النص الكامل
2022
Hassanen, Eman I. | Hussien, Ahmed M. | Mehanna, Sally | Ibrahim, Marwa A. | Hassan, Neven H.
Pesticides are viewed as a major wellspring of ecological contamination and causing serious risky consequences for people and animals. Imidacloprid (IM) and hexaflumuron (HFM) are extensively utilized insect poisons for crop assurance on the planet. A few investigations examined IM harmfulness in rodents, but its exact mechanism hasn’t been mentioned previously as well as the toxicity of HFM doesn’t elucidate yet. For this reason, the present study was designed to explore the mechanism of each IM and HFM–evoked rat liver and kidney toxicity and to understand its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups, as follows: group (1), normal saline; group (2), IM; and group (3), HFM. Both insecticides were orally administered every day for 28 days at a dose equal to 1/10 LD50 from the active ingredient. After 28 days postdosing, rats were anesthetized to collect blood samples then euthanized to collect liver and kidney tissue specimens. The results showed marked changes in walking, body tension, alertness, and head movement with a significant reduction in rats’ body weight in both IM and HFM receiving groups. Significant increases in MDA levels and decrease of GHS levels were recorded in liver and kidney homogenates of either IM or HFM groups. Liver and kidney tissues obtained from both pesticide receiving groups showed extensive histopathological alterations with a significant increase in the serum levels of ALT, AST, urea, and creatinine and a decrease in total proteins, albumin, and globulin levels. In addition, there was upregulation of the transcript levels of casp-3, JNK, and HO-1 genes with strong immunopositivity of casp-3, TNF-ὰ, and NF-KB protein expressions in the liver and kidneys of rats receiving either IM or HFM compared with the control group. In all studied parameters, HFM caused hepatorenal toxicity more than those induced by IM. We can conclude that each IM and HFM provoked liver and kidneys damage through overproduction of ROS, activation of NF-KB signaling pathways and mitochondrial/JNK-dependent apoptosis pathway.
اظهر المزيد [+] اقل [-]The inducing of caspase and Bcl-2 pathway with royal jelly decreases the muscle tissue damage exposed with fluoride in rats النص الكامل
2022
Aslan, Abdullah | Can, Muhammed Ismail | Gok, Ozlem | Beyaz, Seda | Parlak, Gozde | Ozercan, Ibrahim Hanifi
In this study, 42 Wistar albino male rats (n = 42, 8 weeks old) were used. Rats were divided into 6 groups and 7 rats included each group. Groups: (i) Control group: Standard diet; (ii) RJ (royal jelly) group: Standard diet + royal jelly; (iii) F50 group: Standard diet + 50 mg/kg fluoride; (iv): F100 group: Standard diet + 100 mg/kg fluoride; (v) F50+RJ group: Standard diet + 50 mg/kg fluoride + royal jelly; (vi): F100+RJ group: Standard diet + 100 mg/kg fluoride + royal jelly. After 8 weeks, the rats were decapitated, and their muscle tissues were removed. Expression levels of Caspase-3, Caspase-6, Bax, tumor necrosis factor-α (TNF-α), interleukin 1 alpha (IL1-α) and Bcl-2 proteins in muscle tissue were determined by western blotting method. Histopathological analyses were also performed on the muscle tissue. Malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) analyses were determined by a spectrophotometer. According to the obtained results, Bcl-2, TNF-α and IL1-α protein expression was increased in damage groups compared to the control and royal jelly groups, while Caspase-3, Caspase-6 and Bax protein expression levels decreased in damage groups. MDA level increased in damage groups compared to the control and royal jelly groups, while CAT and GSH levels increased with royal jelly application in royal jelly-given group in comparison to the flouride-exposed group. According to histopathological analysis results, edema and inflammatory cell formations were found in the injury groups, a tendency to decrease in these injuries was observed in the treatment groups. Based on these results, we can say that royal jelly has protective effects on muscle tissue against fluoride damage.
اظهر المزيد [+] اقل [-]