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Chronic pesticide exposure induced aberrant Notch signalling along the visual pathway in a murine model
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.
Show more [+] Less [-]Oil induces chlorophyll deficient propagules in mangroves
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.
Show more [+] Less [-]Generation of albino via SLC45a2 gene targeting by CRISPR/Cas9 in the marine medaka Oryzias melastigma
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.
Show more [+] Less [-]Role of Platelet-activating factor and HO-1 in mediating the protective effect of rupatadine against 5-fluorouracil-induced hepatotoxicity in rats
2022
Khalaf, Hanaa Mohamed | Hafez, Sara Mohamed Naguib Abdel | Abdalla, Ahlam Mohamed | Welson, Nermeen N. | Abdelzaher, Walaa Yehia | Abdelbaky, Fatma Alzhraa Fouad
5-fluorouracil (5-FU) is a widely used chemotherapeutic drug, but its hepatotoxicity challenges its clinical use. Thus, searching for a hepatoprotective agent is highly required to prevent the accompanied hepatic hazards. The current study aimed to investigate the potential benefit and mechanisms of action of rupatadine (RU), a Platelet-activating factor (PAF) antagonist, in the prevention of 5-FU-related hepatotoxicity in rats. Hepatotoxicity was developed in male albino rats by a single 5-FU (150 mg/kg) intra-peritoneal injection on the 7th day of the experiment. RU (3 mg/kg/day) was orally administrated to the rodents for 10 days. Hepatic toxicity was assessed by measuring both liver and body weights, serum alanine aminotransferase and aspartate aminotransferase (ALT and AST), hepatic oxidative stress parameters (malondialdehyde (MDA), nitric oxide levels (NOx), reduced glutathione (GSH), superoxide dismutase (SOD)), and heme oxygenase-1 (HO-1). Inflammatory markers expressions (inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukins; IL-1B, IL-6), the apoptotic marker (caspase-3), and PAF were measured in the hepatic tissue. 5-FU-induced hepatotoxicity was proved by the biochemical along with histopathological assessments. RU ameliorated 5-FU-induced liver damage as proved by the improved serum ALT, AST, and hepatic oxidative stress parameters, the attenuated expression of hepatic pro-inflammatory cytokines and PAF, and the up-regulation of HO-1. Therefore, it can be concluded that RU pretreatment exerted a hepatoprotective effect against 5-FU-induced liver damage through both its powerful anti-inflammatory, antioxidant, and anti-apoptotic effect.
Show more [+] Less [-]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]
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.
Show more [+] Less [-]Aloe vera protects against fluoride-induced teratogenic effects during pre- and postnatal development in mice
2022
Pregnancy and feto-gestational toxicities on exposure to fluoride and its possible amelioration on co-administration with aloe vera were studied in pregnant Swiss albino mice. Once the confirmed pregnancy was tested, animals were equally divided into four groups as follows: group I was given no treatment and served as control, and groups II and III were administered with 100 and 300 ppm sodium fluoride, respectively, while group IV was co- administered aloe vera (300 mg/kg bw) along with sodium fluoride (300 ppm) daily for 14 days prior to gestation and continued till the 18th day of gestation. Animals were sacrificed on the 19th day of gestation for prenatal observations. Maternal body weight, the gravid uterine weight, number of corpora lutea in both the ovaries, number of implantations and resorptions, number of live (mature and immature) fetuses, and number of dead fetuses were examined in each dam. The treatment continued in another set of animals till the completion of the weaning period to observe postnatal changes due to test substances on the mother and pups. Sodium fluoride–treated animals showed morphometric and skeletal changes which were more pronounced in the high-dose group showing significantly decreased body weight gain in pregnant mothers and dead/immature fetuses. Morphometric changes included open eyelids, limb defects, wrinkles on the whole body, anophthalmia, pulmonary edema, enlarged esophagus, and decreased body weight of fetuses and pups. Alizarin-prepared skeletal structures of fetuses of such female mice showed delayed ossification or bending in the number of bones of skull, thoracic, and limb regions. However, concomitant exposure to sodium fluoride and aloe vera in treated animals led to a marked improvement in all the prenatal and postnatal variables. The study suggests that sodium fluoride at high concentrations may be teratogenic while co-administration of aloe vera during fluoride exposure might be beneficial in reducing these toxic effects. The use of aloe vera as a preventive agent or as a complimentary agent is thus recommended following fluoride exposure through the oral route.
Show more [+] Less [-]Histopathological, Immunohistochemical, And Molecular Alterations In Brain Tissue And Submandibular Salivary Gland Of Atrazine-Induced Toxicity In Male Rats
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.
Show more [+] Less [-]Nanoplastics-induced oxidative stress, antioxidant defense, and physiological response in exposed Wistar albino rats
2022
Babaei, Ali Akbar | Rafiee, Mohammad | Khodagholi, Fariba | Ahmadpour, Elham | Amereh, Fatemeh
Nowadays, plastic pollution and in particular nano(micro)plastics is considered as an issue of global concern in environmental samples. The present work was conducted to clarify the oxidative stress of polystyrene nanoplastics (PS-NPs) exposure and physiological response of male Wistar rats. Animals were treated orally with PS-NPs at four doses (1, 3, 6, and10 mg/kg-day) for 5 weeks. Results demonstrated the accumulation of PS-NPs through whole body scanning and also a dose-dependent increase in the production of reactive oxygen species (ROS). Alterations in antioxidant responses including serum levels of catalase (CAT) and total glutathione content were noticed, but not superoxide dismutase (SOD), pointing towards the perturbation of redox state induced by exposure conditions. Biochemical parameters viz. glucose, cortisol, lipase, lactate, lactate dehydrogenase (LDH), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), triglycerides, and urea showed a significant increase, while total protein, albumin, and globulin levels showed an appreciable decline. The pattern of associations noticed with AChE activity and biochemical responses in our study suggests the possibility that a neurobehavioral effect or dysfunctions in energy metabolism may be the potential modes of action, possibly through stress response as well as liver function. Perturbations of creatinine and uric acid levels are indeed plausible biological explanations for the association with kidney dysfunction. Although we provided a new scientific clue for exploring the biological consequences of NPs which might induce effects such as oxidative stress relating to the induction of antioxidant enzymes, the results warrant additional research with a larger sample size.
Show more [+] Less [-]Wound healing properties of green (using Lawsonia inermis leaf extract) and chemically synthesized ZnO nanoparticles in albino rats
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.
Show more [+] Less [-]Oxidative stress, apoptosis and histopathological alterations in brain stem and diencephalon induced by subacute exposure to fipronil in albino rats
2022
Awad, Mohamed A. | Ahmed, Zainab Sabry Othman | AbuBakr, Huda O. | Elbargeesy, Gehad Abd El-Fattah Hassan | Moussa, Moukhtar H. G.
Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress–induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.
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