Browsing by Author "Sachin Yadav"

Now showing 1 - 2 of 2

NMR based Serum metabolomics revealed metabolic signatures associated with oxidative stress and mitochondrial damage in brain stroke
(Springer, 2024) Sachin Yadav; Abhai Kumar; Smita Singh; Shahnawaz Ahmad; Gurvinder Singh; Abdul Rahman Khan; Rameshwar Nath Chaurasia; Dinesh Kumar
Brain stroke (BS, also known as a cerebrovascular accident), represents a serious global health crisis. It has been a leading cause of permanent disability and unfortunately, frequent fatalities due to lack of timely medical intervention. While progress has been made in prevention and management, the complexities and consequences of stroke continue to pose significant challenges, especially, its impact on patient’s quality of life and independence. During stroke, there is a substantial decrease in oxygen supply to the brain leading to alteration of cellular metabolic pathways, including those involved in mitochondrial-damage, leading to mitochondrial-dysfunction. The present proof-of-the-concept metabolomics study has been performed to gain insights into the metabolic pathways altered following a brain stroke and discover new potential targets for timely interventions to mitigate the effects of cellular and mitochondrial damage in BS. The serum metabolic profiles of 108 BS-patients were measured using 800 MHz NMR spectroscopy and compared with 60 age and sex matched normal control (NC) subjects. Compared to NC, the serum levels of glutamate, TCA-cycle intermediates (such as citrate, succinate, etc.), and membrane metabolites (betaine, choline, etc.) were found to be decreased BS patients, whereas those of methionine, mannose, mannitol, phenylalanine, urea, creatine and organic acids (such as 3-hydroxybutyrate and acetone) were found to be elevated in BS patients. These metabolic changes hinted towards hypoxia mediated mitochondrial dysfunction in BS-patients. Further, the area under receiver operating characteristic curve (ROC) values for five metabolic features (methionine, mannitol, phenylalanine, mannose and urea) found to be more than 0.9 suggesting their high sensitivity and specificity for differentiating BS from NC subjects. Graphical abstract: [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Toxicity of Pentachlorophenol Exposure on Male and Female Heteropneustes fossilis Investigated Using NMR-Based Metabolomics Approach
(American Chemical Society, 2025) Sonam Singh; Sachin Yadav; Radha Chaube; Dinesh Kumar
Pentachlorophenol (PCP) is one of the most common chlorophenols utilized in numerous industrial processes, including the production of dyes, pesticides, wood preservatives, disinfectants, antiseptics, and medicines because it has fungicidal and bactericidal characteristics. Previous studies on catfish (Heteropneustes fossilis) revealed that PCP acts as a potent endocrine disruptor and also causes behavioral changes in a concentration-dependent manner. However, the toxicological effects of PCP have not been compared between male and female catfish. The present study aims to investigate the toxic effects of PCP on catfish through histopathological changes, oxidative stress, and serum metabolomics after 60 days of exposure. Chronic exposure to sublethal concentrations of PCP resulted in significant histopathological alterations in the liver and gonad, including leukocyte infiltration, hepatocyte degeneration, follicular layer dissolution, and abnormal sperm distribution. Increased levels of lipid peroxidation and hydrogen peroxide, along with decreased antioxidant enzyme activity, were observed in PCP-exposed groups. A 1H NMR-based metabolomics approach was employed to investigate the toxic effects of PCP on catfish serum, revealing alterations in various metabolites, including amino acids, organic acids, glucose, cholesterol, and neurotransmitters, in a dose-dependent manner. Multivariate partial least-squares discriminant analysis (PLS-DA) identified metabolic changes associated with oxidative stress, disruption in hormone synthesis and reproduction, disturbance in osmoregulation and membrane stabilization, energy metabolism disorder, amino acid metabolism disorder, and neurotransmitter imbalance in PCP-exposed catfish. This study demonstrates the efficacy of metabolomics in elucidating the toxicity and underlying mechanisms of wood preservatives like PCP, providing valuable insights for risk assessment in toxicology research. Overall, these findings contribute to our understanding of the toxicological effects of PCP exposure on aquatic organisms and highlight the potential of histology, oxidative stress, and metabolomics in assessing environmental contaminants’ risks. © 2025 The Authors. Published by American Chemical Society.