Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats

Chlorpyrifos (CPF) has been considered as one of the most potent organophosphates and is linked to several neurological disorders. On the other hand, Quercetin is a vital plant flavanoid and has been reported to regulate a number of physiological processes in the central nervous system. The present study was conducted to investigate the protective potential of quercetin during chlorpyrifos induced neurotoxicity. Female Wistar rats weighing 150–200?g were divided into four different groups viz: Normal control, CPF treated (13.5?mg/kg.b.wt. every alternate day), Quercetin treated (50?mg/kg.b.wt./day) and combined CPF and quercetin-treated. All the treatments were carried out for a total duration of eight weeks. Chlorpyrifos treatment showed significant alterations in the cognitive behavior and motor activities of rats, which were appreciably improved upon simultaneous supplementation with quercetin. Further, CPF treatment caused a significant inhibition in the enzyme activities of acetylcholinesterase and choline acetyltransferase, but caused an increase in the levels of acetylcholine in the brain. Further, chlorpyrifos exposure significantly elevated the levels of lipid peroxidation and protein carbonyl contents as well as the activities of catalase, superoxide dismutase, which were interestingly found to be decreased following co-treatment with quercetin. In contrast, CPF treatment decreased the activities of glutathione reductase, transferase, as well as levels of reduced and total glutathione in both the cerebrum and cerebellum but co-administration of quercetin, increased these levels. Chlorpyrifos treatment altered the neuro-histoarchitecture, which showed improvement upon quercetin supplementation. Hence, this study suggests that quercetin can be used as a prophylactic intervention to prevent CPF induced neurotoxicity.     

Novel analogs of sulfasalazine as system xc− antiporter inhibitors: Insights from the molecular modeling studies

System x_c⁻ (Sx_c⁻), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sx_c⁻. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sx_c⁻ antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sx_c⁻ inhibitory activity following in vitro Sx_c⁻ inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.     

A potent enzybiotic against methicillin-resistant Staphylococcus aureus

Virus Genes - Staphylococcus aureus is one of the most dreadful infectious agents, responsible for high mortality and morbidity in both humans and animals. The increased prevalence of...     

Interaction of pretilachlor with PS-II activity of the cyanobacterium Desmonostoc muscorum PUPCCC 405.10

Interaction of pretilachlor with photosystem (PS)-II of the cyanobacterium Desmonostoc muscorum PUPCCC 405.10 has been studied in this paper. Pretilachlor negatively affected growth, chlorophyll a (Chl a), photosynthesis, and carbon dissimilation in a dose-dependent manner. Effects were also observed in PSs, especially PS-II (an 11–35% decrease), as well as the whole photosynthetic electron transport activity. The fluorescence emission spectrum of Chl a revealed a dose-dependent effect of pretilachlor on both the antenna and the core complex of PSs, with more severe effect on the former. Data of O-J-I-P fluorescence transient of Chl a revealed that pretilachlor interfered with electron flow between Q_A and Q_B sites of PS-II. It was further observed that pretilachlor decreased maximum fluorescence, variable and relative variable fluorescence, maximum quantum yield, quantum yield of electron transport, the rate of trapped exciton movement, quantum yield of electron transfer, and performance index of primary photochemistry; however, there was a progressive increase in the net rate of PS-II closure, quantum yield of energy dissipation, and effective antenna size per active reaction center. A decrease in photosynthetic activity leads to a decrease in carbon dissimilation, as evidenced by low activity of glucose-6-phosphate dehydrogenase and pyruvate kinase. Thus, pretilachlor, which is otherwise known to kill weeds by interfering with cell division, affected the growth of the cyanobacteria by interacting with PS-II.