Exploring the link between pyrethroids exposure and dopaminergic degeneration through morphometric, immunofluorescence, and in-silico approaches: the therapeutic role of chitosan-encapsulated curcumin nanoparticles

Introduction: The synthetic pyrethroid derivative fenpropathrin (FNE), a commonly used insecticide, has been associated with various toxic effects in mammals, particularly neurotoxicity. The study addressed the hallmarks of the pathophysiology of Parkinson's disease upon oral exposure to fenpropathrin (FNE), mainly the alteration of dopaminergic markers, oxidative stress, and molecular docking in rat models. In addition, the protective effect of curcumin-encapsulated chitosan nanoparticles (CRM-Chs-NPs) was also assessed. Methods: In a 60-day trial, 40 male Sprague Dawley rats were divided into 4 groups: Control, CRM-Chs-NPs (curcumin-encapsulated chitosan nanoparticles), FNE (15 mg/kg bw), and FNE + CRM-Chs-NPs. Results: FNE exposure induced reactive oxygen species generation, ATP production disruption, activation of inflammatory and apoptotic pathways, mitochondrial function and dynamics impairment, neurotransmitter level perturbation, and mitophagy promotion in rat brains. Molecular docking analysis revealed that FNE interacts with key binding sites of dopamine synthesis and transport proteins. On the other hand, CRM-Chs-NPs mitigated FNE's toxic effects by enhancing mitochondrial dynamics, antioxidant activity, and ATP production and promoting anti-inflammatory and antiapoptotic responses. Conclusion: In summary, FNE appears to induce dopaminergic degeneration through various mechanisms, and CRM-Chs-NPs emerged as a potential therapeutic intervention for protecting the nervous tissue microenvironment

Forensic toxicological study on adipocere formation in submerged cadavers of female albino rats intoxicated with cadmium

There is a dearth of information on the mutual interaction between metal intoxication and adipocere formation. Herein, 40 adult female albino rats were distributed into two equal groups, one used as control while the other orally administered single dose of cadmium chloride (CdCl2) 225 mg/kg·bw (LDmin). Control group was killed by cervical dislocation. Half of dead rats of both groups were subjected for determination of iodine value and estimation of cadmium (Cd) residues while the other half of both groups were submerged in opened glass container previously filled with 4 L dechlorinated tap water kept in closed room with an open air access (one cadaver/container). Gross morphological changes of submerged cadavers were recorded weekly along the experiment. At the end of the experiment, after 3 months, samples were collected again for iodine value determination and estimation of Cd residues. The obtained results revealed the depressant effect of Cd toxicity on development of adipocere. Cd residues were found in different tissues of cadavers at time of death with the highest amount in the intestines followed by the liver and kidneys, then lungs, adipose tissue, muscles, and finally the bones. After 3 months of water submersion, tissues exhibited significant decrease in the amount of Cd residues but to a limit that was still detected. This study concluded the possibility of detection of Cd residues even after adipocere formation. Additionally, it shed light on the possibility of the interference of environmental pollution with the natural rate of decomposition especially adipocere formation

Pancreatic Response to Gold Nanoparticles Includes Decrease of Oxidative Stress and Inflammation In Autistic Diabetic Model

Background: Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt. Results: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. Conclusions: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs

Palliative Effect of Resveratrol against Nanosized Iron Oxide-Induced Oxidative Stress and Steroidogenesis-Related Genes Dysregulation in Testicular Tissue of Adult Male Rats

The nano-sized iron oxide (Fe2O3-NPs) is one of the most used engineered nanomaterials worldwide. This study investigated the efficacy of natural polyphenol resveratrol (RSV) (20 mg/kg b.wt, orally once daily) to alleviate the impaired sperm quality and testicular injury resulting from Fe2O3-NPs exposure (3.5 or 7 mg/kg b.wt, intraperitoneally once a week) for eight weeks. Spermiograms, sexual hormonal levels, oxidative stress indicators, and lipid peroxidation biomarker were assessed. Moreover, the steroidogenesis-related genes mRNA expressions were evaluated. The results showed that RSV substantially rescued Fe2O3-NPs-mediated sperm defects. Additionally, the Fe2O3-NPs-induced depressing effects on sperm motility and viability were markedly counteracted by RSV. Moreover, RSV significantly restored Fe2O3-NPs-induced depletion of testosterone, follicle-stimulated hormone, luteinizing hormone, and testicular antioxidant enzymes but reduced malondialdehyde content. Furthermore, the Fe2O3-NPs-induced downregulation of steroidogenesis-related genes (3 β-HSD, 17 β-HSD, and Nr5A1) was significantly counteracted in the testicular tissue of RSV-treated rats. These findings concluded that RSV could limit the Fe2O3-NPs-induced reduced sperm quality and testicular injury most likely via their antioxidant activity and steroidogenesis-related gene expression modulation

Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: An In Vitro Study

This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV) and/or the chemotherapeutic agent bleomycin (BLM) on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20 μg/mL respectively for 24 and 72 hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2). The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity

Effects of Co-Exposure of Nanoparticles and Metals on Different Organisms: A Review

Wide nanotechnology applications and the commercialization of consumer products containing engineered nanomaterials (ENMs) have increased the release of nanoparticles (NPs) to the environment. Titanium dioxide, aluminum oxide, zinc oxide, and silica NPs are widely implicated NPs in industrial, medicinal, and food products. Different types of pollutants usually co-exist in the environment. Heavy metals (HMs) are widely distributed pollutants that could potentially co-occur with NPs in the environment. Similar to what occurs with NPs, HMs accumulation in the environment results from anthropogenic activities, in addition to some natural sources. These pollutants remain in the environment for long periods and have an impact on several organisms through different routes of exposure in soil, water, and air. The impact on complex systems results from the interactions between NPs and HMs and the organisms. This review describes the outcomes of simultaneous exposure to the most commonly found ENMs and HMs, particularly on soil and aquatic organisms

Quercetin Abates Aluminum Trioxide Nanoparticles and Lead Acetate Induced Altered Sperm Quality, Testicular Oxidative Damage, and Sexual Hormones Disruption in Male Rats

This study examined the effects of exposure to lead acetate (PbAc) and/or aluminum trioxide nanoparticles (Al2O3NPs) on testicular function. Additionally, the probable reproprotective effects of quercetin (QTN) against Al2O3NPs and PbAc co-exposure in male Sprague Dawely rats were assessed. Al2O3NPs (100 mg/kg b.wt.), PbAc (50 mg/kg b.wt.), and QTN (20 mg/kg b.wt.) were orally administered for 60 days. Then, spermiogram, histopathological examinations of the testis and accessory glands, and immunohistochemical detection of androgen receptors (AR) and tumor necrotic factor alpha (TNF-α) were achieved. Moreover, serum levels of male sex hormones and testicular levels of antioxidant indices were estimated. The results showed that Al2O3NPs and/or PbAc caused significant sperm abnormalities, testicular oxidative stress, and histopathological changes. Furthermore, serum testosterone, LH, and FSH levels significantly decreased, while estradiol levels significantly increased. The Al2O3NPs and/or PbAc co-exposed group had more obvious disturbances. Furthermore, QTN co-administration significantly reversed the Al2O3NPs and PbAc-induced testicular histopathological alterations, reduced antioxidant defenses, and altered AR and TNF-α immune expression in testicular tissues. Conclusively, Al2O3NPs and/or PbAc evoked testicular dysfunction by inducing oxidative injury and inflammation. However, QTN oral dosing effectively mitigated the negative effects of Al2O3NPs and PbAc by suppressing oxidative stress and inflammation and improving the antioxidant defense system

The Modulatory Role of Vitamin C in Boldenone Undecylenate Induced Testicular Oxidative Damage and Androgen Receptor Dysregulation in Adult Male Rats

Background: This study explored the effect of vitamin C (Vit-C) administration on the reproductive function of adult male Wistar rats injected with boldenone undecylenate (BOL). Methods: Rats were randomly assigned into control, vehicle control, Vit-C (120 mg/kg b.wt./day, orally), BOL (received 5 mg/kg b.wt./week, IM) and BOL+Vit-C-treated groups. After eight weeks, hormonal assay, semen evaluation, testicular enzymes, and antioxidants biomarkers were assessed. Besides, the histopathological and immunohistochemical investigations of the androgen receptor (AR) expression were performed. Results: The results revealed that serum testosterone, acid phosphatase, sorbitol dehydrogenase, sperm abnormalities, and testicular malondialdehyde were significantly incremented in the BOL-treated group. Testicular weight, sperm count, and sperm motility together with serum levels of luteinizing hormone, follicle-stimulating hormone, and estradiol, and testicular testosterone, catalase, superoxide dismutase, and reduced glutathione showed a significant decrease following BOL treatment. Besides, the AR immunoreactivity was significantly decreased in testicular tissues. Vit-C co-administration with BOL significantly relieved the BOL-induced sperm abnormalities, reduced sperm motility, testicular enzyme leakage, and oxidative damage. However, Vit-C could rescue neither BOL-induced hormonal disturbances nor AR down-regulation. Conclusions: The results provide further insight into the mechanisms of BOL-induced reproductive dysfunction and its partial recovery by Vit-C

Investigation of the In-Vivo Cytotoxicity and the In Silico-Prediction of MDM2-p53 Inhibitor Potential of Euphorbia peplus Methanolic Extract in Rats

This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both kidney and heart. The probable underlying mechanism of E. peplus compounds to potentiate p53 activity is examined using Molecular Operating Environment (MOE) docking software and validated experimentally by immunohistochemical localization of p53 protein in the kidney and heart tissues. The gas chromatography/mass spectrometry analysis of E. peplus revealed the presence of nine different compounds dominated by di-(2-ethylhexyl) phthalate (DEHP). Significant elevations of troponin, creatine phosphokinase, creatine kinase–myocardium bound, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and uric acid were evident in the EPME treated rats. The EPME treated rats showed strong renal and cardiac p53 expression and moderate cardiac TNF-α expression. Further, our in silico results predicted the higher affinity and good inhibition of DEHP, glyceryl linolenate, and lucenin 2 to the MDM2-p53 interface compared to the standard reference 15 a compound. Conclusively, EPME long-term exposure could adversely affect the cardiac and renal tissues probably due to their inflammatory and apoptotic activity. Moreover, the in silico study hypothesizes that EPME inhibits MDM2-mediated degradation of p53 suggesting possible anticancer potentials which confirmed experimental by strong p53 expression in renal and cardiac tissues