Activity of paraoxonase 1 in premalignant lesion of the cervix

Paraoksonaza 1 (PON1) je enzim koji sudjeluje u uklanjanju karcinogenih radikala lipidne peroksidacije. Cilj istraživanja je odrediti paraoksonaznu i arilesteraznu aktivnost PON1, razdiobu fenotipova PON1, učestalost polimorfizama gena pon1 koji utječu na enzimsku aktivnost i koncentraciju te parametre lipidnog statusa i oksidacijskoga stresa u ispitanica s premalignim promjenama vrata maternice. Bazalna i NaCl-stimulirana paraoksonazna aktivnost PON1, kao i ove aktivnosti standardizirane na koncentraciju HDL-a i apoAI, ne razlikuju se znatno između kontrolne skupine ispitanica i skupine ispitanica s cervikalnom intraepitelnom neoplazijom (CIN). Arilesterazna aktivnost PON1 te aktivnost standardizirana na koncentraciju HDL-a i apoAI znatno su niže u ispitanica s CIN-om i u ispitanica podijeljenih u podskupine s CIN-om niskog rizika i s CIN-om visokog rizika. Razdioba fenotipova PON1 ne razlikuje se značajno između ispitivanih skupina kao ni razdioba genotipova i alela polimorfizama Q192R, L55M i -108C>T gena pon1. Koncentracija se tiolnih skupina ne razlikuje, dok je koncentracija malondialdehida mnogo niža, a koncentracija glutationa značajno viša u skupini ispitanica s CIN-om. Dobiveni rezultati upućuju na oksidacijsko-antioksidacijsku neravnotežu u žena s CIN-om. Uočeno sniženje arilesterazne aktivnosti PON1 ukazuje na sniženu koncentraciju ovog enzima u serumu žena s CIN-om što može biti posljedica smanjene genske ekspresije uslijed poremećaja redoks homeostaze.Paraoxonase 1 (PON1) is the enzyme that removes carcinogenic radicals of lipid peroxidation. The aim of this study was to determine the paraoxonase and arylesterase activity of PON1, phenotype distribution and polymorphisms of pon1 gene, and parameters of lipid status as well as oxidation stress in patients with premalignant lesion of the cervix. Basal and NaCl-stimulated paraoxonase activity of PON1 as well as those activities standardized on the concentration of HDL and apoAI did not differ significantly between control group and group of patients with cervical intraepithelial neoplasia (CIN). On the other hand, arylesterase activity of PON1 as well as activity standardized on the concentration of HDL and apoAI was significantly reduced in CIN group, and in the subgroups with low grade and high grade changes. Distribution of PON1 phenotypes was similar in the study groups. In addition distribution of genotypes and alleles of Q192R, L55M and -108C>T polymorphisms of pon1 gene did not differ between the study groups. Concentration of thiol groups was similar, of malondialdehide was lower and of glutathione was significantly higher in the CIN groups. Observed results indicated an oxidation-antioxidation disbalance in women with CIN. Decreased arilesterase PON1 activity might reflect reduced enzyme concentration which could be the consequence of down-regulated gene expression due to redox homeostasis disturbances