Arsenic inhibits human salivary aldehyde dehydrogenase: Mechanism and a population-based study

• Published in: Chemosphere (Oxford) Vol. 243; p. 125358
• Main Authors: Younus, Hina, Arsalan, Abdullah, Alam, Md Fazle
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2020
• Subjects: Adult; aldehyde dehydrogenase; Aldehyde Dehydrogenase - metabolism; Arsenic; Arsenic - analysis; Arsenic - toxicity; Arsenic Poisoning; binding sites; Drinking Water; Female; Hazardous Substances - toxicity; Human salivary aldehyde dehydrogenase; Humans; India; Inhibition; inhibitory concentration 50; mass spectrometry; Mechanism; neoplasms; oral health; Population study; Research Design; risk; saliva; Saliva - chemistry; Saliva - metabolism; toxicity; villages; volunteers; India; Human salivary aldehyde dehydrogenase; Inhibition; Arsenic; Population study; Mechanism
• ISSN: 0045-6535; 1879-1298; 1879-1298
• DOI: 10.1016/j.chemosphere.2019.125358

Human salivary aldehyde dehydrogenase (hsALDH) is an important detoxifying enzyme and maintains oral health. Subjects with low hsALDH activity are at a risk of developing oral cancers. Arsenic (As) toxicity causes many health problems in humans. The objective of this population-based study was to correlate As contamination and hence low hsALDH activity with high incidence of cancer cases in Bareilly district of India. Here, it was observed that As inhibited hsALDH (IC50 value: 33.5 ± 2.5 μM), and the mechanism of inhibition was mixed type (in between competitive and non-competitive). Binding of As to hsALDH changed the conformation of the enzyme. A static quenching mechanism was observed between the enzyme and As with a binding constant (Kb) of 9.77 × 104 M−1. There is one binding site for As on hsALDH molecule. Further, the activity of hsALDH in volunteers living in regions of higher As levels in drinking water (Bahroli and Mirganj village of Bareilly district, India), and those living in region having safe levels of As (Aligarh city, India) was determined. The As level in the saliva samples of the volunteers was determined by inductively coupled plasma mass spectroscopy (ICP-MS). Low hsALDH activity was found in volunteers living in the region of higher As levels. The activity of hsALDH and As concentration in the saliva was found to be negatively correlated (r = - 0.427, p < 0.0001). Therefore, we speculate that the high incidence of cancer cases reported in Bareilly district may be due to higher As contamination. •Arsenic (As) toxicity causes many health problems in humans.•Low hsALDH activity is a risk factor for oral cancer development.•This study correlates As contamination, low hsALDH activity and high cancer cases.•Low hsALDH activity was found in volunteers living in regions of high As levels.•Elevated cancer cases in Bareilly (India) may be due to high As contamination.