Plasma Levels of Organochlorine Pesticides and Tumor Necrosis Factor-Alpha: A Potential Risk Factor for Developing Acquired Aplastic Anemia in the North Indian Population

Charu Goel; Nidhish Kumar; Anil K Tripathi; Sunita Tiwari; Ashutosh Shrivastava; Saurabh Shukla; Alok Mishra; Anshuman Srivastava

doi:10.7759/cureus.46122

Plasma Levels of Organochlorine Pesticides and Tumor Necrosis Factor-Alpha: A Potential Risk Factor for Developing Acquired Aplastic Anemia in the North Indian Population

Cureus. 2023 Sep 28;15(9):e46122. doi: 10.7759/cureus.46122. eCollection 2023 Sep.

Authors

Charu Goel^{1

2}, Nidhish Kumar³, Anil K Tripathi⁴, Sunita Tiwari⁵, Ashutosh Shrivastava⁶, Saurabh Shukla⁴, Alok Mishra⁶, Anshuman Srivastava⁶

Affiliations

¹ Physiology, Muzaffarnagar Medical College & Hospital, Muzaffarnagar, IND.
² Physiology, King George's Medical University, Lucknow, IND.
³ Pathology, Autonomous State Medical College, Shahjahanpur, IND.
⁴ Clinical Hematology, King George's Medical University, Lucknow, IND.
⁵ Physiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, IND.
⁶ Centre for Advanced Research, King George's Medical University, Lucknow, IND.

Abstract

Background Pesticide exposure might have a contributory role in the development of acquired aplastic anemia (AA). However, the precise mechanisms of pesticide-induced AA remain unknown. In this case-control study, we conducted a comparative analysis of plasma levels of organochlorine pesticides (OCP) and tumor necrosis factor-alpha (TNF-alpha) between Indian patients diagnosed with AA and an age- and sex-matched control group. Methods This is an observational case-control study conducted at a tertiary care hospital in North India. In this study, 90 subjects were included, out of which 45 were diagnosed with AA according to the criteria of the International Agranulocytosis and Aplastic Anemia Study. Cases were compared with 45 controls. A trained interviewer gave all study subjects a questionnaire to collect data regarding demographic details, exposure to pesticides, and clinical history. Physical examination and routine laboratory investigations of each subject were performed. Both cases and controls were tested for their plasma levels of organochlorines as per established protocol by gas chromatography-mass spectrometry. TNF-alpha level was measured by enzyme-linked immunosorbent assay in each subject. Results There was a significant increase in plasma levels of delta hexachlorocyclohexane (delta HCH) (p = 0.02) and heptachlor (p = 0.00) in patients with AA as compared to controls. We observed nonsignificant trends towards higher levels of beta HCH (p = 0.643), aldrin (p = 0.399), and p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) (p = 0.453) in patients with AA when compared to the controls. There were significantly higher TNF-alpha levels (p = 0.024) in cases as compared to the controls. Conclusion Our study concludes that patients with AA exhibited higher levels of delta-HCH, heptachlor, and TNF-alpha in comparison to the control group. There is a significant positive correlation of TNF alpha with OCPs (alpha HCH, lindane, delta HCH, heptachlor, aldrin, p,p'- DDD, and methoxychlor pesticides). These organochlorines may have accumulated in the fatty tissue of bone marrow because of their lipophilic nature. This suggests that they might have served as a neoantigen to trigger an increase in TNF-alpha production, which may have led to disrupted bone marrow function through cell-mediated immunity, leading to AA.

Keywords: aplastic anemia; delta-hch; gc-ms/ms; heptachlor; mini quechers; organochlorine; pesticide; tumor necrosis factor-alpha (tnfα).

Grants and funding

The authors are grateful to the Indian Council of Medical Research (ICMR), New Delhi, India, for the financial assistance during the study through the Post MD, Ph.D. Program at King George's Medical University, Lucknow.