Structure–function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity

Abstract

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.

Arsenic Speciation in the Blood of Arsenite-Treated F344 Rats

“…Binding of arsenicals with blood proteins can be a critical issue in arsenic speciation in blood. It may alter arsenic metabolism and distribution, and consequently lead to changes in arsenic bioavailability and the kinetics of accumulation and excretion, as well as the function of proteins . For example, transferrin in plasma can reportedly bind to inorganic arsenic instead of methylated arsenic. , A ternary dimethylarsinous-hemoglobin–haptoglobin complex was also detected in rat plasma .…”

Consumption of arsenic-contaminated drinking water and anemia among pregnant and non-pregnant women in northwestern Romania

“…It was observed that arsenic induces oxidative damage to human erythrocytes producing anemia-related changes including alterations in shape, deformability, agreeability, and osmotic fragility (Bollini et al, 2010). Studies in human populations highly exposed to arsenic in drinking water also reported structural and functional hemoglobin and erythrocyte alterations due to oxidative stress, and as a result, diminished oxygen binding affinity (Mondal et al, 2012) and premature cell death (Biswas et al, 2008), alterations likely to lead to clinical anemia.…”

Arsenic and the Cardiovascular System

“…Hb is rich in -SH groups and it is suggested that arsenic and its metabolites may have a propensity to bind to Hb and reduce its binding affinity to oxygen. Recently, Mondal et al [11] studied the binding affinity of trivalent arsenic to Hb and its consequential modification of the structure and function of Hb. Isolated Hb from arsenicosis patients had a binding affinity constant of 0.256 μM −1 with a Hill coefficient of +2.961, suggesting that arsenic molecules modify and lower the binding affinity to oxygen.…”