Neonatal methyl parathion exposure affects the growth and functions of the male reproductive system in the adult rat

Methyl parathion (MP) is a well-known organophosphorus pesticide, to which humans are exposed in fruit and vegetables as residues of 0-2 mg/kg, children being at higher risk of exposure. The present study was planned to investigate the effects on the adult male reproductive functions of MP following neonatal exposure. New born male Wistar rat pups were treated orally with either 0 or 0.5 mg/kg MP from postnatal day (PND) 3 to PND 28 and sacrificed on PND 98 for the purpose of examination of the reproductive system. Methyl parathion lowered the body weights from days 10 to 24 (p < 0.01), the weights of the reproductive organs (p < 0.05-0.01), the epididymal sperm count (p < 0.01) and the homogenisation-resistant testicular spermatid head count (p < 0.01) and also decreased acid phosphatase (ACP), cholesterol, uric acid, protein, ascorbic acid, and lactate dehydrogenase (p < 0.01) levels in the testis but only ACP and cholesterol in the epididymis. The levels of abnormal sperm and testosterone in the testis were increased (p < 0.01), whereas the leutinising hormone level and total number of seminiferous tubules decreased in the testes of treated rats (p < 0.01). A few tubules showed exfoliation of epithelium and vacuoles. The incidence of stage XIV tubules and ratios of meiotic figures and elongating spermatids to Sertoli cell nucleoli decreased (p < 0.01; Mann-Whitney U test). The present results indicate that MP acts as an endocrine disruptor and consequently affects the postnatal development and growth of the male reproductive organs in the rat. These findings are important to the general public, as there is a chance of children being exposed to this pesticide

Molecular docking of fisetin as a multi-target drug in the treatment of Parkinson’s disease

Fisetin is found in various fruits and vegetables. It is reported to have neurotropic, anti-inflammatory, anti-carcinogenic and also other health benefits. Fisetin has been proved to have neuroprotective effect against Parkinson’s disease (PD).&nbsp; Elucidation of the molecular interaction of fisetin with various anti-parkinsonian drug targets leads to better understanding mode of action of the drug. The present study is aimed to study the molecular interaction of fisetin with molecular targets having potential role in PD. The molecular properties and drug likeness model score were first analysed for flavonoid fisetin, which was found to be 0.76. The structures of the molecular drug targets, such as MAO A (2BXR), MAO B (2BYB), COMT (2AVD) and tyrosine hydroxylase (2XSN), was extracted from RCSB-Protein Data Bank. Molecular docking was performed using AUTO DOCK-4.2. The docking scores were evaluated by analyzing the minimum binding energy for the first five runs for all the target proteins. The minimum binding energy for MAO A (2BXR), MAO B (2BYB), COMT (2AVD), tyrosine hydroxylase (2XSN) were -10.22 kcal/mol, -9.68 kcal/mol, -7.45 kcal/mol and -6.67 kcal/mol respectively. Out of the 4 potential PD drug targets, MAO A and MAO, genes responsible for oxidative deamination of dopamine, are predicted to have the least minimum binding energy and best interaction with fisetin. Keywords: Fisetin, docking, multidrug targets, autodock, MAO A, MAO B, COMT, Tyrosine hydroxylas

The reproductive toxicity of the organophosphate pesticide 0, 0-dimethyl 0-4-nitrophenyl phosphorothioate (methyl parathion) in the male rat

Methyl parathion (MP) is a pesticide widely used to protect crops but also illegally used in many countries for spraying homes and businesses to contain insects. The present study was planned to investigate the effects of MP on the male reproductive organs in the rat. Male Wistar rats (13-14 weeks old) were treated with MP and sacrificed as follows. Experiment 1:0 (water vehicle), 1.75, 3.5 or 7 mg/kg (i.p.) for 5 days and sacrificed on day 14; experiment 2:0, 0.5 or 1 mg/kg (i.p.) for 12 days and sacrificed on day 130; experiment 3: 0, 0.5 or 1 mg/kg (i.p.) for 12 days and sacrificed on day 77; experiment 4: 0, 0.75 or 1.5 mg/kg (i.p.) for 25 days and sacrificed on day 17; experiment 5: 0 or 3.5 mg/kg (p.o.) for 25 days and sacrificed on day 17 after the last exposure. The reproductive organs were removed, weighed and processed for histopathological analysis. Structural changes, for example the morphology of the epithelium and the lumina of the organs, were observed in all animals. Biochemical estimates of acid phosphatase (ACP), cholesterol, total protein, uric acid, and vitamin C were conducted in the epididymes. The weight of the epididymes increased in experiment 2 in a dose-dependent pattern (p < 0.01) and decreased in experiments 4 and 5 (p < 0.01). The weight of the ductus deferens decreased in experiment 3 at 1 mg/kg dose level (p < 0.001) and increased in experiment 5 (p < 0.05). The weight of the seminal vesicle decreased in experiment 3 at both 0.5 mg/kg and 1 mg/kg dose levels (p < 0.001), and increased in experiment 5 (p < 0.01). The weight of the prostate decreased in experiments 4 (in a dose-dependent pattern) and 5 (p < 0.001). ACP levels decreased in experiment 4 (p < 0.001) with a greater effect at 0.5 mg/kg than at 1 mg/kg. In experiment 5 (p < 0.01) cholesterol levels decreased to less than 50% of the control level for this experiment (p < 0.01) and protein levels also decreased (p < 0.01). Vitamin C levels decreased in a dose-dependent pattern in experiments 4 (p < 0.001) and 5 (p < 0.01). There were no effects on uric acid level. Sperm density was decreased in the epididymes of the rats treated and the epithelium of the epididymis and ductus deferens showed cellular necrosis, brush-border disruption and nuclear pyknosis. Nuclei were haloed, except in experiment 2 and the 0.5 mg/kg group of experiment 3. Methyl parathion did not induce significant changes in the structure of the seminal vesicle and prostate, except that epithelial folding was shorter than in the control. In conclusion, MP is a reproductive toxicant in the male rat and causes deterioration in the structural integrity of the reproductive organs and also the biochemical parameters in the epididymis

Dielectric properties characterization of La- and Dy-doped BiFeO3 thin films

The dielectric response of La- and Dy- doped BiFeO3 thin films at microwave frequencies (up to 12 GHz) has been monitored as a function of frequency, direct current (dc) electric field, and magnetic field in a temperature range from 25 to 300 °C. Both the real and imaginary parts of the response have been found to be non-monotonic (oscillating) functions of measuring frequency. These oscillations are not particularly sensitive to a dc electric field; however, they are substantially dampened by a magnetic field. The same effect has been observed when the volume of the characterized sample is increased. This phenomenon is attributed to the presence of a limited number of structural features with a resonance type response. The exact origin of these features is unknown at present. Leakage current investigations were performed on the whole set of films. The films were highly resistive with low leakage current, thereby giving us confidence in the microwave measurements. These typically revealed ‘N'-type I-V characteristic

Spectroscopic Characterization and Biological Activity of Mixed Ligand Complexes of Ni(II) with 1,10-Phenanthroline and Heterocyclic Schiff Bases

Mixed ligand complexes of Ni(II) with 1,10-phenanthroline (1,10-Phen) and Schiff bases L1(MIIMP); L2(CMIIMP); L3(EMIIMP); L4(MIIMNP); L5(MEMIIMP); L6(BMIIMP); L7(MMIIMP); L8(MIIBD) have been synthesized. These metal chelates have been characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, Mass, UV-Vis, magnetic moments, and thermogravimetric (TG&DTA) analysis. Spectral data showed that the 1,10-phenanthroline act as neutral bidentate ligand coordinating to the metal ion through two nitrogen donor atoms and Schiff bases acts as monobasic bidentate coordinating through NO donor atoms. All Ni(II) complexes appear to have an octahedral geometry. The antimicrobial activity of mixed ligand complexes has been studied by screening against various microorganisms, it is observed that the activity enhances upon coordination. The DNA binding studies have been investigated by UV-Vis spectroscopy, and the experimental results indicate that these complexes bind to CT DNA with the intrinsic binding constant Kb=2.5±0.2×105 M−1. MTT is used to test the anticancer effect of the complexes with HL60 tumor cell. The inhibition ratio was accelerated by increasing the dosage, and it had significant positive correlation with the medication dosage

Exploring common genetic contributors to neuroprotection from amyloid pathology

Preclinical Alzheimer’s disease describes some individuals who harbor Alzheimer’s pathologies but are asymptomatic. For this study, we hypothesized that genetic variation may help protect some individuals from Alzheimer’s-related neurodegeneration. We therefore conducted a genome-wide association study using 5,891,064 common variants to assess whether genetic variation modifies the association between baseline beta-amyloid, as measured by both cerebrospinal fluid and positron emission tomography, and neurodegeneration defined using MRI measures of hippocampal volume. We combined and jointly analyzed genotype, biomarker, and neuroimaging data from non-Hispanic white individuals who were enrolled in four longitudinal aging studies (n=1065). Using regression models, we examined the interaction between common genetic variants (Minor Allele Frequency > 0.01), including APOE-ε4 and APOE-ε2, and baseline cerebrospinal levels of amyloid (CSF Aβ42) on baseline hippocampal volume and the longitudinal rate of hippocampal atrophy. For targeted replication of top findings, we analyzed an independent dataset (n=808) where amyloid burden was assessed by Pittsburgh Compound B ([{11}^C]-PiB) PET. In this study, we found that APOE-ε4 modified the association between baseline CSF Aβ42 and hippocampal volume such that APOE-ε4 carriers showed more rapid atrophy, particularly in the presence of enhanced amyloidosis. We also identified a novel locus on chromosome 3 that interacted with baseline CSF Aβ42. Minor allele carriers of rs62263260, an expression quantitative trait locus for the SEMA5B gene, (p=1.46x10^{-8}; 3:122675327) had more rapid neurodegeneration when amyloid burden was high and slower neurodegeneration when amyloid was low. The rs62263260 x amyloid interaction on longitudinal change in hippocampal volume was replicated in an independent dataset (p=0.0112) where amyloid burden was assessed by PET. In addition to supporting the established interaction between APOE and amyloid on neurodegeneration, our study identifies a novel locus that modifies the association between beta-amyloid and hippocampal atrophy. Annotation results may implicate SEMA5B, a gene involved in synaptic pruning and axonal guidance, as a high-quality candidate for functional confirmation and future mechanistic analysis

Economic effect of mechanical intervention through sub-soiling on growth and yield of rainfed pigeonpea (Cajanus cajan)

A two-year field experiment was conducted to investigate the effect of sub-soiling on plant growth, root morphology and yield of rainfed pigeonpea [Cajanus cajan (L. ) Millsp.] (Var LRG 41) during 2012-13 and 2013-14. Crop exposed to moisture stress condition from flowering to harvest (120 days) during 2013-14, compared to experiment conducted during 2012-13. The results indicated that sub-soil tillage sustained higher shoot, root growth and seed yield during the year 2013-14, which coincided with end of season drought compared to conventional tillage treatment. Crop growth in terms of plant height, leaf area/plant significantly improved due to sub-soiling compared to conventionally tilled treatment. Similarly sub-soiling recorded significant increase in drought tolerant traits, viz. root length (234%), root dry weight (274%) and relative water content (37%). Consequently, sub-soil tillage recorded significant increase in number of pods/plant by 59%, 100 seed weight by 12% and pod yield by 219% compared to conventionally tilled treatment. Sub-soil tillage proved efficient method of mechanical intervention for drought mitigation under rainfed pigeonpea cultivation