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Journal Article 
Structure-function alteration of hemoglobin in arsenicosis patients: A probable pathway to exert toxicity 
Mondal, B; Chatterjee, D; Bhattacharyya, M 
In Press 
Journal of Applied Toxicology
ISSN: 0260-437X
EISSN: 1099-1263 
Chronic arsenicosis, a major public health concern in India and Bangladesh, is mainly caused by ingestion of arsenic (As) contaminated ground water. Although this problem has been studied extensively, the mechanism of toxicity remains unknown. This paper investigates the process of trivalent arsenicals binding to hemoglobin (Hb) in chronic arsenicosis patients and consequent modification in the structure-function activity of Hb. In this work peroxidase activity, thermal denaturation profile, oxygen releasing capacity and hydrodynamic diameter have been evaluated for the Hb collected from subjects suffering with chronic arsenicosis. Increased peroxidative activity suggests altered oxidative status of Hb in the diseased state. The thermal denaturation profile indicates the Hb molecule to be more susceptible to unfolding in the pathologic state. The enhanced oxygen releasing capacity and significant reduction in hydrodynamic diameter of Hb is also observed in the diseased condition, suggesting conformational alterations in the Hb molecule. Finally, trivalent arsenic is found to bind with freshly isolated Hb from arsenicosis patients, binding affinity constant being 0.256 μM(-1) . The binding is positively cooperative with a Hill coefficient of +2.961 and isosbestic points at specific wavelengths. Thus, our work explores the structure-function property of Hb in chronic arsenicosis subjects and reveals that the molecule is modified in such a way that comparatively weak binding with oxygen and strong binding with arsenic occur simultaneously. This association may play a crucial role in exerting the pathway for arsenic toxicity. Copyright © 2011 John Wiley & Sons, Ltd. 
chronic arsenicosis; hemoglobin; peroxidative activity; thermal denaturation; oxygen release; hydrodynamic diameter; Hill coefficient 
• Arsenic Hazard ID
     1. Initial Lit Search
          Considered New
     2. Lit Search Updates through Oct 2015
     4. Considered through Oct 2015
     5. Additions through Oct 2015
     6. Cluster Filter through Oct 2015
     7. Other Studies through Oct 2015
          Noncancer MOA Seeds
• Arsenic (Inorganic)
     1. Literature
          Toxline, TSCATS, & DART
          Web of Science
          Lit search updates through Oct 2015
     3. Hazard ID Screening
          Other potentially supporting studies
     4. Adverse Outcome Pathways/Networks Screening
     5. Susceptibility Screening
          Excluded/Not relevant
• Arsenic MOA
     4. Adverse Outcome Pathways
     1. MOA Literature Screening
          MOA Seeds
          MOA Cluster
          Susceptibility Screening
• Arsenic Susceptibility
     5. Health Effect
          Hematology, Hematopoietic System
     1. Susceptibility Literature Screening
          Keyword Search
     2. Excluded
     3. References Identified During Review