Antioxidant enzyme plays a pivotal role in preventing oxidative stress. Chemical toxicants often exert adverse effects in the biological system by breaking the antioxidant response system leading to severe oxidative stress. N-Ethyl-N-Nitrosourea (ENU) is a DNA alkylating agent and is carcinogenic and neurotoxic in animals. ENU in the nervous system cause persistent alkylation of DNA within the neurons altering the normal functional activities of the brain. Prenatal exposure to ENU in rodents that generate malignant gliomas in the brain induces functional changes and apoptotic death in neuronal progenitors in the brain's subventricular zone (SVZ). However, as chemical toxicants, their role in the induction of oxidative stress in brain tissue and subsequent change in the brain were less studied. In this study, we have investigated the response antioxidant system and induction of oxidative stress in the Balb/c mice brain at various time points after ENU exposure. Exposures to ENU were found to raise the oxidative stress and lipid peroxidation in the brain of mice with subsequent reduction in antioxidant enzyme activity. A significant increase in lactate dehydrogenase activity in the serum and brain homogenate was recorded at 16th weeks after ENU injection, which indicates metabolic alteration due to damage in the brain and has been validated by histological damage in the cerebral cortex and abnormal neurologic behavior in animals administered with ENU.
IntroductionCurrent anti-leukemic chemotherapies with multiple targets suffer from side effects. Synthetic drugs with huge off-target effects are detrimental to leukemic patients. Therefore, natural plant-based products are being increasingly tested for new anti-leukemic therapy with fewer or no side effects. Herein, we report the effect of ethanolic olive leaves extract (EOLE) on the K562 cell line and on the bone marrow (BM) of N-ethyl-N-nitrosourea (ENU)-induced leukemic mice.MethodsUsing standard methodologies, we assessed viability, chromatin condensation, and induction of apoptosis in EOLE-treated K562 cells in-vitro. The anti-leukemic activity of EOLE was assayed by measuring ROS, levels of various cytokines, expression of iNOS and COX-2 gene, and changes in the level of important apoptosis regulatory and cell signaling proteins in-vivo. ResultK562 cells underwent apoptotic induction after exposure to EOLE. In the BM of leukemic mice, EOLE therapy decreased the number of blast cells, ROS generation, and expression of NF-κB and ERK1/2. IL-6, IL-1β, TNF-α, iNOS, and COX-2 were among the inflammatory molecules that were down-regulated by EOLE therapy. Additionally, it decreased the expression of anti-apoptotic proteins BCL2A1, BCL-xL, and MCL-1 in the BM of leukemic mice.DiscussionChronic inflammation and anomalous apoptotic mechanism both critically contribute to the malignant transformation of cells. Inflammation in the tumor microenvironment promotes the growth, survival, and migration of cancer cells, accelerating the disease. The current investigation showed that EOLE treatment reduces inflammation and alters the expression of apoptosis regulatory protein in the BM of leukemic mice, which may halt the progression of the disease.
[Cu2(μ‐2‐chlorobenzoato‐O,O’)4Cl2].2(4‐DMAPH) (1) and [Zn2(μ‐2‐chlorobenzoato‐O,O’)4(4‐DMAP)2] (2) (4‐DMAP=4‐Dimethylaminopyridine) were synthesized from CuCl2/Zn(NO)3)2 . 6H2O, 2‐chlorobenzoic acid and 4‐dimethylaminopyridine in methanol under reflux. Compounds were comprehensively characterized by elemental analyses, conductance measurement, spectroscopic and X‐ray diffraction studies. Complexes crystallized in the monoclinic space group P21/n having dinuclear paddle‐wheel structure. DFT studies along with NCI plot, QTAIM analysis indicate presence of N−H⋯Cl, C−H⋯O, C−H⋯π interactions in 1 and CH3⋯π, π⋯π and C−H⋯Cl in 2. The charge distribution in the complexes was shown via MEP analysis. Complexes interact with CT‐DNA in moderately strong non‐intercalative mode of binding. Antimicrobial study against Shigella flexneri (B), Streptococcus pneumoniae (K), Klebsiella pneumoniae (P) and Shigella boydii (Q) shows appreciable activity of 1 whereas compound 2 is comparatively less active. In vitro cytotoxicity study against cell lines (L‐132) exhibits moderate activity by the complexes, but compound 2 shows significant cell inhibition activity against cell lines K‐562. The complexes are emissive in nature.
Availability of safe drinking water at the railway stations is a basic passenger amenity. To maintain the quality of drinking water, the Ministry of Railways, Government of India, follow the Uniform Drinking Water Quality Monitoring Protocol, 2013, with a benchmarking standard of Bureau of Indian Standards, 2012. The quality of drinking water varies from state to state, including station to station, due to the diversified regional structure of the country. The regional structure of Tripura, Northeastern state of India, is unique for its Tilla-Lunga topography, where 27 railway stations provide passenger services, including safe drinking water of heterogeneous quality. The present study aims to assess and develop a model of drinking water quality at the railway stations of Tripura, India, with a possible strategic solution. Multivariate statistical tools like multiple regression analysis, principal component analysis, and cluster analysis have been used. Weighted Arithmetic Water Quality Index (WAWQI) and Entropy Weighted Water Quality Index (EWWQI) have been applied to assess the drinking water quality of the railway stations of Tripura. It has been observed that several physical ( r = 0.42, p -value = 0.064), chemical ( r = 0.31, p -value = 0.047), and biological ( r = 0.47, p -value = 0.077) parameters of drinking water are positively correlated with each other, whereas chloride ( λ = 2.98), E. coli ( λ = 2.13), turbidity ( λ = 1.72), fluoride ( λ = 1.49), and iron ( λ = 1.08) are most significant water quality parameters in the railway stations of Tripura. The WAWQI and EWWQI classified the drinking water of 55.55% and 85.19% of railway stations as good for drinking, respectively. Drinking water quality can improve 55.55% to 81.48% by removing iron content from the water. Physiography and land use patterns of surrounding areas of railway stations influence drinking water quality. Elevation and urbanisation have significant negative correlation (− 0.438 and − 0.441 at 5% level) with drinking water quality. Policy-practice interference has been analysed, and passenger satisfaction with drinking water has been measured for the bottom-up planning approach. Through content analysis, a few technical suggestions have been made to improve the physio-chemical and biological properties of drinking water at the railway stations of Tripura.
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