Cardiotoxicity is an imperative issue in the assessment of heavy metal consumption and inorganic arsenic (As). These have a cardiotoxic effect which is evaluated by biochemical, and ...oxidative-antioxidant tests, and by the Nrf2- HO-1 pathway. Dried ginger powder is recognized for its efficient antioxidant activities and as a protector of the cardiovascular system from toxic damage caused by heavy metals. However, the possible function of ginger against As in heart via heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2) is unclear. A total of 120 White Pekin ducks were randomly distributed into groups comprising 24 birds in each. Each group comprised 3 replicates having 8 birds in each replicate. The time period of this study was 90 days. The groups were the control Group I whereas groups II to IV were fed a basal diet including arsenic at 28 mg/L. Dried ginger powder as an ameliorative agent was mixed with the basal diet and fed at 0.1, 0.3 and 1 g/kg feed to groups III, IV and V, respectively. In the current experiment, dried ginger powder decreased As-induced reactive oxygen species (ROSs) production, oxidative injury and pathological modifications. In addition, cardiac dysfunction factors, intracellular calcium (Ca2+), As accumulation and cAMP deficiency levels were noticed in ducks; these alternations were attenuated by ginger. Furthermore, ginger significantly altered the down regulation of both HO-1 and Nrf2 gene expressions caused by As. Thus, the proven protective role of ginger against As-induced cardiotoxicity may be a consequence of the maintenance of redox homeostasis, i.e. the Nrf2-HO-1 pathway and by enabling As efflux.
A significant health issue, reproductive toxicity is mostly linked to exposure to various environmental heavy metals. A pervasive toxin that occurs naturally in the environment is arsenic (As). This ...research was done to determine the effects of various doses of inorganic As supplements on the reproductive organs of adult male white Pekin ducks. A total of 240 numbers of 14-days-old male white Pekin ducks were weighed and randomly assigned into 4 experimental groups with six replicates (10 ducklings in each replicate). The experimental groups were as follows: (T-1) basal diet along with normal drinking water (control group); (T-2 to T-4) basal diet along with As in the form of sodium-meta-arsenite at 7, 14, and 28 ppm of drinking water respectively. The results showed reduction in body weight and testicular weight, disruption of spermatogenesis, reduction in follicular-stimulating hormone (FSH), leutinizing hormone (LH), and testosterone levels and histopathological alterations as compared to control. Additionally, there was not only a significant decrease in various antioxidant parameters in testis tissue, like catalase (CAT), reduced glutathione (GSH), super oxide dismutase (SOD), and ferric-reducing antioxidant power (FRAP), but also a significant increase in oxidative parameters of testis like lipid peroxidation (LPO), myloperoxidase (MPO), nitric oxide (NO), and super oxide anion radical (O
2
−
) in As-treated groups, in comparison with T-1. A significantly higher level of As content in testis was observed in all the 3 As-treated groups, with highest level recorded in T-4 birds. Besides that, there was upregulation of nuclear factor kappa B (NF-
κ
B), heat shock proteins (Hsps) and pro-inflammatory cytokines like interlukin (IL) series, i.e., IL-2, IL-6, IL-18, IL-1β and tumor necrosis factor- α (TNF-α) levels, whereas anti-inflammatory parameters like IL-4 and IL-10 levels showed downregulation in testis of As-treated groups. Together, these findings provide deeper understandings of the roles played by oxidative stress, NF-
κ
B and Hsps in the progression of testicular injury, which may help to explain how the As induced male sterility, in ducks, due to exposure.
The toxic metalloid arsenic is known to cause liver and kidney injury in many humans and animals. The goal of this paper was to exemplify the antagonism of ginger against arsenic (As)-induced ...hepato-renal toxicity. In addition, the pathways Nrf2/Keap1 and NF/κB were studied to reveal the molecular mechanism of the stress. One hundred twenty 7-day-old White Pekin ducks were randomly allocated into five groups, having 24 birds in each. Each group contained three replicates having 8 birds in each replicate and maintained for 90 days. The groups were as follows: T-1 control-basal diet with normal water, T-2 T1 + As at 28 ppm/L of water, T-3 T2 + ginger powder at 100 mg/kg feed, T-4 T2 + ginger powder at 300 mg/kg feed, and T-5 T2 + ginger powder at 1 g/kg feed. It was observed that there was a significant increase in oxidative parameters whereas a significant decrease in antioxidant parameters in hepato-renal tissues in T-2. The exposure to As not only decreased the mRNA expression of antioxidant parameters like Nrf2, SOD-1, CAT, GPX, and HO-1and anti-inflammatory markers like IL-4 and IL-10 but also increased the m-RNA expression of NF-κB, Keap-1 and pro-inflammatory markers like IL-2, Il-6, IL-18, IL-1β, and TNF-α. There was also an accumulation of As in hepatic and renal tissue, confirmed by residual analysis of these tissues. By correlating the above parameters, As at 28 ppm showed significant toxic effects, and ginger powder at 1 g/kg feed effectively counteracted the toxic effects of As in ducks.
Human oral squamous cell carcinoma is the sixth most frequent malignant cancer, with an unacceptably high death rate that affects people's health. Albeit, there are several clinical approaches for ...diagnosing and treating oral cancer they are still far from ideal. We previously synthesised and characterised the docetaxel nanoformulation (PLGA-Dtx) and discovered that docetaxel nanoencapsulation may suppress oral cancer cells. The goal of this study was to figure out the mechanism involved in the suppression of oral cancer cell proliferation. We discovered that PLGA-Dtx inhibited SCC-9 cell growth considerably as compared to free docetaxel (Dtx), and that the viability of SCC-9 cells treated with PLGA-Dtx was decreased dose-dependently. MTT assay showed that PLGA-Dtx selectively inhibited the growth of PBMCs from oral cancer patients while sparing PBMCs from normal healthy controls. Further, flow cytometry analysis showed that PLGA-Dtx induced apoptosis and necroptosis in SCC-9 cells. G2/M cell cycle arrest has been confirmed on exposure of PLGA-Dtx for 24 h in SCC-9 cells. Interestingly, western blot investigation found that PLGA-Dtx increased the amounts of necroptic proteins and apoptosis-related proteins more efficiently than Dtx. Furthermore, PLGA-Dtx was more effective in terms of ROS generation, and mitochondrial membrane potential depletion. Pretreatment with necroptosis inhibitor Nec-1 efficiently reversed the ROS production and further recover MMP caused by PLGA-Dtx. Overall, this study revealed a mechanistic model of therapeutic response for PLGA-Dtx in SCC-9 cells and proposed its potency by inducing cell death via activation of concurrent apoptosis and necroptosis in SCC-9 cells via TNF-α/RIP1/RIP3 and caspase-dependent pathway.
Kardiotoksičnost je vrlo važna u procjeni problema koji nastaju konzumacijom teških metala. Anorganski arsen
(As) ima kardiotoksičan učinak koji se procjenjuje na temelju biokemijskih, ...oksidacijsko-antioksidacijskih nalaza te na
temelju puta Nrf2-HO-1. Sušeni đumbirov prah poznat je po svojoj učinkovitoj antioksidacijskoj aktivnosti i zaštitnom
djelovanju u slučaju intoksikacije kardiovaskularnog sustava teškim metalima. Nejasna je međutim uloga đumbira u
odnosu na arsen u srčanom mišiću putem hem-oksigenaze 1 (HO-1) i faktora 2 povezanog s nuklearnim eritroidnim
faktorom. Ukupno je 120 bijelih pataka pasmine pekinška patka nasumično podijeljeno u skupine koje su sadržavale
po 24 jedinke. U svakoj skupini provedena su 3 ponovljena postupka (replikacije) na po 8 jedinki. Ukupno je vrijeme
istraživanja bilo 90 dana. Skupina I bila je kontrolna skupina koja nije primila ni arsen ni đumbir. Pokusnim skupinama
od II do V je, uz osnovnu prehranu, u različitim kombinacijama dodavan arsen u dozi od 28mg/L i sušeni đumbirov prah u dozama od 0,1g/kg 0,3g/kg i 1 g/kg. Rezultati su pokazali da je sušeni đumbirov prah smanjio prisutnost reaktivnih vrsta kisika (ROS) uzrokovanu arsenom, oksidacijsko oštećenje i patološke promjene. Osim toga uočene promjene, kao što su su faktori srčane disfunkcije, unutarstanični kalcij (Ca2+), nakupljanje arsena i deficijencija razine cAMP-a, ublažene su đumbirovim prahom. Đumbir je, nadalje, znakovito utjecao na smanjenje genske ekspresije i HO-1 i Nrf2 uzrokovane arsenom. Zaključeno je da bi zaštitna uloga đumbira u slučaju kardiotoksičnosti uzrokovane arsenom mogla biti posljedica održavanja redoks homeostaze, odnosno puta Nrf2-HO-1 i omogućavanja eliminacije arsena.
Bioceramic materials based biological implants have gained enormous attention in research due to their extensive medical application. However, release of wear debris from them limits their clinical ...relevance due to many health risks in the recipient. Thus, we decided to evaluate the cytotoxicity and genotoxicity of wear debris released from Strontium oxide doped Zirconia Toughened Alumina (SrO-ZTA) hip prosthesis developed in our laboratory. An extensive cytotoxicity analysis confirms that the cellular and nuclear morphology of C2C12 mouse myoblast cells are intact even after 72 h of SrO-ZTA wear debris exposure. Furthermore, treatment of wear debris in Drosophila model did not cause any damage to the larval gut epithelium and nuclei. Despite the reactive oxygen species (ROS) increase in third instar larvae after wear debris treatment at higher concentrations (50–100 μg/mL), the flies show appreciable weight gain, suggesting no harm to larva and flies. Interestingly, the eye, wing, and bristles of the hatched flies of all the experimental groups do not show any phenotypic defects. However, the number of pupae formed and flies hatched for SrO-ZTA wear debris treatment groups are almost similar to control groups expect higher treatment concentration (100 μg/mL). Lastly, the current study establishes the non-cytotoxic and non-genotoxic nature of SrO-ZTA wear debris in-vitro and in-vivo, suggesting promising medical relevance of SrO-ZTA composite.
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•SrO-ZTA is non-cytotoxic and promotes growth of C2C12 mouse myoblast cells.•Oral intake of SrO-ZTA nanocomposite has no toxic effect on the fly behaviour.•No nuclear damage and oxidative stress level were observed in D. melanogaster.•In vitro and in vivo studies validate SrO-ZTA as a non-toxic biocomposite.
Novelty: The non-cytotoxic and non-genotoxic properties of SrO-ZTA composite based wear debris can be used in several biomedical applications. The larger size of dispersed wear debris (micrometer range) as compared to the size of previously reported wear debris (nanometer range) makes the wear debris less cytotoxic and genotoxic.
Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We ...therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India.
The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines.
From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years IQR 41–66 vs the European and US registries; p<0·0001) and more likely to be men (1249 56·9% of 2195). Previous tuberculosis (780 35·5% of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 13·7%) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03–1·32; p=0·015), P aeruginosa infection (1·29, 1·10–1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07–1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25–1·39; p<0·0001), daily sputum production (1·16, 1·03–1·30; p=0·013), and radiological severity of disease (1·03, 1·01–1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins.
Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India.
EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.
Background and Objectives: Genital tuberculosis (TB) is an important cause of infertility in women that poses many challenges in diagnosis. The study is done to understand the utility of GeneXpert ...test in peritoneal fluid in the diagnosis of genital TB in infertile women. Methods: All infertile women in postmenstrual phase who were planned for laparoscopy in study period were included. Women who were already on anti-TB therapy were excluded. Peritoneal fluid/washings were retrieved during laparoscopy to test for Mycobacterium tuberculosis by GeneXpert. A note was made of laparoscopy evidence of TB. Endometrial sample was sent for microbiological testing of mycobacterium on smear and liquid culture. Histopathological test of endometrium was also done to look for granulomas. Results: In a total of 57 women, 8 (14.03%) women were diagnosed with TB on the basis of laparoscopy or microbiological or histopathological tests. Six women had caseating tubercles in pelvis, of them two women had presence of mycobacterium on smear, one woman also had positive liquid culture. In two women endometrial smear was positive. None of the women had a positive GeneXpert test in peritoneal fluid. Conclusion: Genital TB is a clinical problem in infertile women. Even in women with confirmed genital TB the peritoneal fluid/washings were negative for mycobacterium. GeneXpert did not pick Mycobacterium in peritoneal fluid in women with genital TB. Hence, it is not a sensitive and good tool for the diagnosis of female genital TB.
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