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Reproductive Toxicology (Elmsford, N.Y.) Apr 2022Environmental contamination with hexavalent chromium, Cr(VI), has been increasing in the United States as well as in developing countries. Exposure to Cr(VI) predisposes...
Environmental contamination with hexavalent chromium, Cr(VI), has been increasing in the United States as well as in developing countries. Exposure to Cr(VI) predisposes the human population to various diseases, including cancer, infertility, and developmental problems in children. Previous findings from our laboratory reported that prenatal exposure to Cr(VI) caused premature ovarian failure through p53-mediated mechanisms. Sirtuin 1 (SIRT1) is an NAD+ -dependent histone deacetylase class III. SIRT1 deacetylates several histones and non-histone proteins such as p53 and NFkB. The current study determines a role for the SIRT1-p53 network in apoptosis induced by Cr(VI) in the ovary and establishes physical interaction between SIRT1 and p53. Adult pregnant dams were given regular drinking water or Cr(VI) (10 ppm potassium dichromate in drinking water, ad libitum), and treated with SIRT1 inhibitor, EX-527 (50 mg/kg body weight, i.p.,), during 9.5 - 14.5 days post-coitum. On postnatal day-1, ovaries from F1 offspring were collected for various analyses. Results indicated that Cr(VI) increased germ cell and somatic cell apoptosis, upregulated acetyl-p53, activated the apoptotic pathway, and inhibited cell survival pathways. Cr(VI) decreased acetyl-p53-SIRT1 co-localization in the ovary. In an immortalized rat granulosa cell line SIGC, Cr(VI) inhibited the physical interaction between SIRT1 and acetyl-p53 by altering the p53:SIRT1 ratio. EX-527 exacerbated Cr(VI)-induced mechanisms. The current study shows a novel mechanism for Cr(VI)-induced apoptosis in the ovary, mediated through the p53-SIRT1 network, suggesting that targeting the p53 pathway may be an ideal approach to rescue ovaries from Cr(VI)-induced apoptosis.
Topics: Animals; Apoptosis; Chromium; Female; Ovary; Pregnancy; Rats; Sirtuin 1; Tumor Suppressor Protein p53
PubMed: 35307491
DOI: 10.1016/j.reprotox.2022.03.007 -
Actas Dermo-sifiliograficas Jun 2022Contact dermatitis is a common reason for consultation in dermatology. Sensitization levels and frequency, however, vary from one population to the next. The aim of this...
BACKGROUND AND OBJECTIVES
Contact dermatitis is a common reason for consultation in dermatology. Sensitization levels and frequency, however, vary from one population to the next. The aim of this study was to review patch test results showing sensitization to allergens in the Spanish standard series in the Canary Islands, where a large proportion of the population works in tourism.
MATERIAL AND METHODS
Retrospective, descriptive study of data from the dermatology department's contact dermatitis unit at Complejo Hospitalario Universitario Insular in Las Palmas de Gran Canaria, Spain. We studied results recorded for patients patch tested with the Spanish standard series between January 2005 and June 2018.
RESULTS
Data for 1568 patients were studied; 71.6% were women, and overall rates of atopy (14.2%) and occupational dermatitis (15.8%) were low. Most patients with a positive test (65.2%) were older than 40years. The main allergens eliciting positive reactions were nickel (36.5%), methylchloroisothiazolinone/methylisothiazolinone (11.9%), methylisothiazolinone (11.8%), paraphenylenediamine (7.5%), and potassium dichromate (6.3%).
CONCLUSIONS
Contact sensitization rates were higher than those reported elsewhere in Spain for most of the allergens studied. The differences were particularly notable for nickel, methylchloroisothiazolinone/methylisothiazolinone, and paraphenylenediamine.
Topics: Allergens; Dermatitis, Allergic Contact; Female; Humans; Male; Nickel; Patch Tests; Retrospective Studies; Spain
PubMed: 35292236
DOI: 10.1016/j.ad.2022.02.027 -
Research in Pharmaceutical Sciences Apr 2022Kidney diseases impose significant global health challenges. Potassium dichromate (PD) is a heavy metal frequently associated with nephrotoxicity. PD prompts oxidative...
BACKGROUND AND PURPOSE
Kidney diseases impose significant global health challenges. Potassium dichromate (PD) is a heavy metal frequently associated with nephrotoxicity. PD prompts oxidative and inflammatory injuries in renal tissues. L-carnitine is a naturally-occurring amino acid commonly used as a supplement.
EXPERIMENTAL APPROACH
Forty rats were randomly allocated into 5 groups. Group 1 (normal) received only saline. Nephrotoxicity was induced in the remaining groups by PD (15 mg/kg; i.p). Group 2 served as a nephrotoxic group. Groups 3-5 received L-carnitine (25, 50, and 100 mg/kg; p.o.), respectively for 4 weeks.
FINDINGS/RESULTS
PD administration resulted in elevated serum creatinine and blood urea nitrogen accompanied by diminished reduced glutathione and elevated malondialdehyde, tumor necrosis factor-alpha, and transforming growth factor-beta renal tissue contents relative to normal rats. PD also produced apoptotic histopathological injuries and down-regulated PI3K/Akt signaling pathway; signifying ongoing apoptosis. In the current work, L-carnitine use in the selected dose levels resulted in improvement of all the aforementioned serum, renal tissue, and histological parameters relative to nephrotoxic rats. L-carnitine up-regulated PI3K/Akt signaling pathway that was down-regulated post PD use.
CONCLUSION AND IMPLICATIONS
Collectively, the study highlighted that the possible mechanisms beyond the beneficial effects of L-carnitine are mainly through its antioxidant as well as anti-inflammatory actions. L- carnitine significantly abrogated apoptosis up-regulation of PI3K/Akt signaling pathway and signified restoration of normal renal cell proliferation and functionality.
PubMed: 35280839
DOI: 10.4103/1735-5362.335174 -
Animals : An Open Access Journal From... Jan 2022This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr)-induced toxicity. Potassium dichromate (KCrO)...
This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr)-induced toxicity. Potassium dichromate (KCrO) and selenium-enriched yeast (SeY) were used to construct the single Cr and combined Se/Cr exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr group, and Cr group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr; however, these changes were mitigated by Se/Cr exposure. Importantly, Cr exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Crgroup. Furthermore, Cr significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Crgroup than in the Cr group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr groups, while they were downregulated in Se/Cr group compared to that in Cr group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr exposure, but the SeY supplement relived the expression levels mediated by Cr exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr, and we speculate that the NF-κB signaling pathway is one of its mechanisms.
PubMed: 35049769
DOI: 10.3390/ani12020146 -
Data in Brief Feb 2022The data were obtained by a label-free quantification approach from a shotgun proteomics experiment, using STrap sample processing technique for protein digestion and...
The data were obtained by a label-free quantification approach from a shotgun proteomics experiment, using STrap sample processing technique for protein digestion and high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) for peptide analysis. MaxQuant data processing was used to obtain proteomics data. The dataset reflects changes in the liver protein profile of Japanese medaka exposed to 0, 5, 40 and 80 mg/L nominal concentrations of Sigma-Aldrich humic acid for 96 h. Actual concentrations of humic acid were measured using the potassium dichromate photometric method and reported in mg organic carbon/L. These proteomics data are relevant for further insights into fish stress responses to humic substances-related challenge.
PubMed: 35036493
DOI: 10.1016/j.dib.2022.107796 -
Toxicology Reports 2022The study compares the toxicity of 53 selected medicinal plants commonly used in the Philippines to treat various diseases. It uses as a benchmark L., which was...
The study compares the toxicity of 53 selected medicinal plants commonly used in the Philippines to treat various diseases. It uses as a benchmark L., which was approved by the Philippine Food and Drug Administration as an herbal drug for cough and asthma after passing clinical trials for safety and efficacy. The methods were chosen for their simplicity and accessibility even for resource-limited laboratories. Extracts (95 % ethanol) of the medicinal parts of the plants were (1) chemically profiled using qualitative phytochemical tests that detect the presence of key classes of bioactive compounds; and (2) evaluated for toxicity using the brine shrimp ( sp.) lethality assay (BSLA). General phytochemical screening revealed the presence of tannins in 50 plant extracts, alkaloids in 43, glycosides in 33, flavonoids in 31, steroids in 21, triterpenoids in 20, anthraquinones in 10, and saponins in 8. Extracts from eight plants had LC values lower than the potassium dichromate control (approximately 12 μg/mL) and were considered highly toxic; extracts from 21 plants had LC values between 12 μg/mL and 100 μg/mL and were considered moderately toxic; extracts from 19 plant extracts, including Vitex negundo and some common vegetables, had LC values between 100 μg/mL and 500 μg/mL, and were considered mildly toxic and likely to have reasonable safety margins; five plant extracts, including common vegetables, had LC values above 500 μg/mL and were considered essentially nontoxic. No apparent correlation could be found between toxicity and chemical diversity or a specific class of phytochemicals present. Our findings may serve as a guide for herbal drug and nutraceutical development, especially in prioritizing plants for more detailed safety studies.
PubMed: 34976744
DOI: 10.1016/j.toxrep.2021.12.002 -
Indian Journal of Pharmacology 2021Stress exacerbates the pathophysiology of major neurodegenerative disorders. In this study, the zebrafish (Danio rerio), the frequently used model for experimental...
OBJECTIVE
Stress exacerbates the pathophysiology of major neurodegenerative disorders. In this study, the zebrafish (Danio rerio), the frequently used model for experimental studies of stress and other central nervous system disorders, was used to evaluate the anxiolytic potential of flavonoids, namely silibinin and naringenin on alleviating acute stress-induced anxiety.
MATERIALS AND METHODS
A molecular docking study with Molegro Virtual Docker software was done to assess the binding potential of flavonoids on serotonin and dopamine receptors. To determine the bioactivity and investigate the toxicity of the flavonoids, silibinin, and naringenin, brine shrimp lethality assay, and an acute toxicity study was conducted according to Organization for Economic Co-operation and Development (OECD) Test Guideline 203. The effect of silibinin and naringenin was assessed using behavioral tasks such as the novel tank assay and the light-dark test on the zebrafish model of acute stress.
RESULTS
Molecular docking studies showed a higher affinity of silibinin and naringenin for the serotonin and dopamine receptors. In comparison to the LC value, 13.15 μg/ml of the reference standard potassium dichromate, silibinin, and naringenin yielded higher LC values, 34.10 μg/ml and 91.33 μg/ml, respectively. The LC value of silibinin and naringenin was observed to be >100 mg/l from the acute toxicity study on adult zebrafish. After transferring to a novel tank, silibinin and naringenin-treated zebrafish groups were found to explore the upper level of the tank, similar to standard drugs, and spent a long time in the upper level of the tank compared to the control group (p < 0.01). Both silibinin and naringenin treatment group spent increased amounts of time in the tank's illuminated part in contrast to that of the dark side as evidenced by the number of zebrafish entering or remaining in the illuminated part of the tank through the light-dark test. Silibinin and naringenin treated groups were found to spend increased time in the light side significantly on the day 15 of evaluation as compared to the control group (p < 0.05 and p < 0.001, respectively).
CONCLUSION
The flavonoids, silibinin, and naringenin were found to mitigate acute stress-induced anxiety, owing to their anxiolytic properties in the zebrafish model and may be explored as the potential therapeutic agents for treating anxiety.
Topics: Animals; Anti-Anxiety Agents; Anxiety Disorders; Artemia; Behavior, Animal; Citrus; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Flavanones; Inhibitory Concentration 50; Male; Silybum marianum; Molecular Docking Simulation; Phytotherapy; Random Allocation; Silybin; Zebrafish
PubMed: 34975133
DOI: 10.4103/ijp.IJP_18_20 -
Annals of Parasitology 2021Gastrointestinal (GI) infection is predominant globally, especially in people with low socio-economic status with existing illiteracy, ignorance, poor housing and...
Gastrointestinal (GI) infection is predominant globally, especially in people with low socio-economic status with existing illiteracy, ignorance, poor housing and lifestyle, and the surrounding environment. It has been implicated as a significant public health concern in the rural parts of many developing countries like Nepal. This study aimed to determine the diversity and prevalence of GI parasites in the highly marginalized indigenous Chepang communities in central Nepal. One hundred fresh stool samples of Chepangs were collected and preserved in 2.5% potassium dichromate solution. The samples were analyzed by direct wet mount, sedimentation, flotation, and acid-fast techniques and examined under the microscope at the total magnifications of 100Å~, 400Å~, and 1000Å~. We detected 97% prevalence rates with eight protozoan and six helminth parasites. Considering the infection’s concurrency, mixed pattern of infection was found to be higher than single pattern. Mixed infections from two to seven parasitic species were differently recorded in different samples. We also found that people’s eating habits were associated with GI parasitism (p=0.0034). “One Health” Approach/Principle accompanied by the detailed molecular and epidemiologic studies of parasitic transmission is required to identify the causal evidence critical in controlling and preventing parasitic infections.
Topics: Animals; Cross-Sectional Studies; Feces; Humans; Intestinal Diseases, Parasitic; Nepal; Parasites; Prevalence; Risk Factors
PubMed: 34953115
DOI: 10.17420/ap6703.353 -
European Review For Medical and... Dec 2021Quercetin (Qct) is a flavonoid that belongs to the group of the most bioactive polyphenolic compounds. It is abundantly found in our diet, and it has many beneficial... (Review)
Review
Quercetin (Qct) is a flavonoid that belongs to the group of the most bioactive polyphenolic compounds. It is abundantly found in our diet, and it has many beneficial effects on human health because of its potent antioxidant properties. Qct has shown cardioprotective effects against doxorubicin, cyclophosphamide, daunorubicin, and lindane and nephroprotective effects against methotrexate, doxorubicin, gentamicin, valproic acid, cadmium, potassium dichromate, fluoride, mercury chloride, 2,3,7,8-tetrachlorodibenzo-p-dioxin, titanium dioxide nanoparticles, and gold nanoparticles. In the current review, we discussed the molecular and biochemical mechanisms involved in the cardio- and nephroprotective effects of Qct. The main purpose of this review was to identify the cardio- and the nephroprotective mechanisms of Qct against several drugs and chemicals to encourage further studies to investigate the potential protective effect of Qct.
Topics: Animals; Antioxidants; Cardiotonic Agents; Cardiotoxicity; Humans; Kidney Diseases; Metal Nanoparticles; Protective Agents; Quercetin
PubMed: 34919245
DOI: 10.26355/eurrev_202112_27440 -
Microbiology Spectrum Dec 2021Soil-transmitted helminths (STH) are important and widespread intestinal pathogens of humans and animals. It is presently unknown which inactivating procedures may be...
Soil-transmitted helminths (STH) are important and widespread intestinal pathogens of humans and animals. It is presently unknown which inactivating procedures may be universally effective for safe transport, preservation, and disinfection of STH-contaminated specimens, and this lack of knowledge may expose laboratory staff to higher risk of laboratory-acquired infections (LAI's). There are limited data on the efficacy of commonly used disinfectants and fecal fixatives for inactivating the eggs of STH. This work tested five disinfectants for surface cleanup, four storage temperature conditions, and six transport/storage fixatives, to inactivate eggs of three species of STH of animal origin ( "roundworm," "whipworm" and Ancylostoma caninum "hookworm") as surrogates for human STH. Among disinfectants, exposure to 10% povidone-iodine for ≥5 min inactivated 100% of the three species tested, while 5 min exposure to 95% ethanol inactivated and A. caninum eggs. All of the fixatives tested had inactivation effects on A. caninum hookworm eggs within 24 h of exposure, except potassium dichromate, which required 48 h. 95% ethanol for ≥48 h inactivated eggs from all three STH species. Freezing at ≤-20°C for ≥24 h inactivated eggs of and A. caninum, but only freezing at -80°C for ≥24 h inactivated >99% eggs, including . This work provides an evidence base for health and safety guidelines and mitigation strategies for the handling, storage, and disposal of stool samples containing STH eggs in laboratory, health care, childcare, or veterinary settings. This study systematically evaluates common laboratory disinfectants and storage conditions for their effectiveness in inactivating the infective stages of soil-transmitted helminths (STH). Animal-infecting proxy species were chosen to represent three major groups of STH that infect humans: roundworms, whipworms, and hookworms. Previously published work in this area typically focuses on a particular inactivation method, either for a single STH species, or on a subset of closely related species. Because prediagnostic fecal specimens must be regarded as potentially infectious with a mix of species, such information may be of limited utility in a working laboratory. We provide a straightforward summary of storage and disinfection methods that can achieve complete inactivation across a range of STH species, which represents a significant advance for clinical, veterinary and research laboratory biosafety.
Topics: Ancylostoma; Ancylostomatoidea; Animals; Anti-Infective Agents, Local; Ascaris suum; Containment of Biohazards; Disinfectants; Disinfection; Ethanol; Feces; Helminths; Hookworm Infections; Humans; Ovum; Povidone-Iodine; Soil; Specimen Handling; Trichuris
PubMed: 34908464
DOI: 10.1128/Spectrum.01828-21