Effect of activated glycyrrhizic acid on epithelial cell lipidome in HPV-associated cervical lesions: A prospective cohort study

Abstract

Aim. To determine the change of lipid levels in the cervical epithelial cells during the treatment of chronic cervicitis and low-grade squamous intraepithelial lesions (LSIL) with 0.1% activated glycyrrhizic acid. Materials and methods. The prospective cohort study included 40 patients with chronic cervicitis and 40 patients with LSIL. Cytological evaluation of cervical smears was performed according to the Bethesda system (2014). All patients received Epigen Intim Spray for 18 months. Amplification of type-specific DNA fragments of human papillomavirus (HPV) and human DNA (sampling control SC) was done using a kit of reagents to detect, type, and quantitatively determine 21 HPV types by Quantum-21 HPV PCR. Lipid extract of a cervical epithelial scraping taken before and after therapy was analyzed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Lipids were identified using the Lipid Match R-script and by characteristic MS/MS. Correlation analysis of the lipidome of cervicovaginal fluid and SC was performed using the Spearman test, and the Mann-Whitney test was used to compare lipid levels at the two time points. Results. During the treatment of chronic cervicitis, the levels of CL lipids 16:0_16:1_18:1_18:1, HexCer-NDS d20:0/26:0, PC 16: 0_18: 1 and 16: 0_20:4 were decreasing; during the treatment of LSIL, the levels of ceramides and glucosylceramides were decreasing. Chronic cervicitis is characterized by a positive correlation of SC smear with cardiolipins, glucosylceramides, and epithelial lipids with an ether bond; LSIL showed a negative correlation with phosphatidylcholines and phosphatidylethanolamines with an ether bond. Conclusion. As a result of treatment with activated glycyrrhizic acid, the lipid spectrum of epithelial cells significantly changed, depending on the type of lesion. It is also necessary to consider SC scrapings in further studies of epithelial cell lipidome and the type of HPV-associated lesions that affects the adjustments.