Arsenic toxicity and immunosuppression

Exposure to arsenic (As) is a global public health problem because of its association with various cancers and numerous other pathological effects, and millions of people worldwide are exposed to as on a regular basis.

Arsenic toxicity and immunosuppressionAs enter into the human body via oral route as the residues of As are present in the food items and water. Increasing lines of evidence indicate that As may adversely affect the immune system, but its specific effects on immune function are poorly understood.

Metabolism in the body:

Inorganic As exists in the environment as arsenite (AsIII) or arsenate (AsV) and is metabolized in humans via conversion of AsV to AsIII with subsequent methylation to mono- and di-methylated arsenicals (MMA and DMA, respectively).

MMAIII is considered the most toxic arsenical and individuals who excrete a higher proportion of ingested As as urinary MMA have increased risks of As-associated cancers, suggesting a key role for MMA in As toxicity.

Mechanism of toxicity:

Proposed mechanisms of toxicity include oxidative stress, inhibition of DNA repair, chromosomal aberrations, micronuclei formation, induction of apoptosis, modification of cellular signaling via altered activation,

Expression and DNA binding activity of transcription factors, epigenetic modifications resulting in aberrant gene expression, and altered phenotype of stem cell populations.

Mechanism of immunosuppression:

As significantly impacts both innate and adaptive immune defenses. The as cause the immunosuppression by following ways.

i) Reduces the expression of MHC class II molecules, CD69, IL-1β and TNF-α

ii) Alters the expression of airway adhesion- and migration-related genes/proteins

iii) Decreases stimulated lymphocyte proliferation and IL-2 secretion

iv) Impairs the macrophage adhesion, phagocytosis and stimulated ROS production involving altered Rho A-ROCK signaling

v) Induces apoptosis of PBMC (Peripheral Blood Mononuclear cells)

vi) Decreases the stimulated ROS production by PBMC

These effects result in immunosuppression, as evidenced by reduced microbial clearance in animals and increased prevalence of opportunistic infections in humans, particularly RTI.

Discussion:

Aresenic an immunomodulator that could render the host immunocompromised. Such immune alterations could help explain increased risk of infections and several cancers observed in chronically-exposed human populations.

Moreover, inconsistencies in epidemiological findings, possibly due to differences in dose, sampling, genetic background, and environmental nutritional factors, indicate need for larger participant numbers and diverse ethnic populations.

Due to differential effects of exposures, populations having low, intermediate and high exposure should be evaluated to better understand dose-dependent relationships.

Furthermore, strong evidence for an association between developmental As exposure and elevated risk of human disease necessitates more investigations of early-life exposure outcomes.

Conclusion:

Finally, comprehensive genomic, proteomic and metabolomic profiling will be critical for identifying and validating potential molecular targets of As to monitor progression of As-associated diseases and elucidate mechanisms of As immunotoxicity.

Authors: Ashiq Ali*1, Aisha Khatoon1, Zain- Ul- Abidin2, Muhammad Tariq Javed.

1 Department of Pathology, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan. 2 Veterinary Research Institute, Lahore, Pakistan.

* Corresponding Author Email: drashiq3485@gmail.com

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