Folate derivatives, 5‑methyltetrahydrofolate and 10‑formyltetrahydrofolate, protect BEAS‑2B cells from high glucose–induced oxidative stress and inflammation.

Ajana, Pathikkal and Bijesh, Puthusseri and Divya, P. and Sudha, R. and Chauhan, V. S. (2022) Folate derivatives, 5‑methyltetrahydrofolate and 10‑formyltetrahydrofolate, protect BEAS‑2B cells from high glucose–induced oxidative stress and inflammation. In Vitro Cellular & Developmental Biology - Animal, 58. pp. 419-428.

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Abstract

Folate (vitamin B9) and its biologically active derivatives are well-known antioxidant molecules protecting cells from oxida�tive degradation. The presence of high glucose, often found in diabetic patients, causes oxidative stress resulting in cellular stress and infammatory injury. Cells in organs such as the lung are highly prone to infammation, and various protective mechanisms exist to prevent the progressive disorders arising from infammation. In the present study, the synthetic form of folate, i.e. folic acid, and active forms of folate, i.e. 5-methyltetrahydrofolate and 10-formyltetrahydrofolate, were evaluated for their antioxidant and antiinfammatory potential against high glucose (50 mM)–mediated oxidative stress and infamma�tion in BEAS-2B cells, an immortalised bronchial epithelial cell line. High glucose treatment showed a 67% reduction in the viability of BEAS-2B cells, which was restored to the viability levels seen in control cultures by the addition of active folate derivatives to the culture media. The DCFH-DA fuorometric assay was performed for oxidative stress detection. The high glucose–treated cells showed a signifcantly higher fuorescence intensity (1.81- and 3.8-fold for microplate assay and microscopic observation, respectively), which was normalised to control levels on supplementation with active folate deriva�tives. The proinfammatory NF-κB p50 protein expression in the active folate derivative–supplemented high glucose–treated cells was signifcantly lower compared to the folic acid treatment. In support of these fndings, in silico microarray GEN�VESTIGATOR database analysis showed that in bronchiolar small airway epithelial cells exposed to infammatory condi�tion, folate utilization pathway genes are largely downregulated. However, the folate-binding protein gene, which encodes to the folate receptor 1 (FOLR1), is signifcantly upregulated, suggesting a high demand for folate by these cells in infam�matory situations. Supplementation of the active folate derivatives 5-methyltetrahydrofolate and 10-formyltetrahydrofolate resulted in signifcantly higher protection over the folic acid from high glucose–induced oxidative stress and infammation. Therefore, the biologically active folate derivatives could be a suitable alternative over the folic acid for alleviating infam�matory injury-causing oxidative stress.

Item Type:	Article
Uncontrolled Keywords:	Antioxidant · Diabetes · Folate receptor · Lung · Inflammation
Subjects:	600 Technology > 08 Food technology > 16 Nutritive value > 04 Vitamins 600 Technology > 08 Food technology > 32 Antioxidants
Divisions:	Plant Cell Biotechnology
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	25 Jan 2023 04:40
Last Modified:	25 Jan 2023 04:40
URI:	http://ir.cftri.res.in/id/eprint/15868

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