CHLORPYRIFOS IN HUMAN PLACENTA: EFFECTS IN CES AND PON ACTIVITY AND EXPRESSION

RODRIGUEZ, PIUQUE M.; VERA, BERTA; BURGOS, CAROLINA; MIGLIORANZA, KARINA S.B.; RAMIREZ, CRITINA L.; LAVALLE, ANDREA; ONDARZA, PAOLA M.; GUIÑAZU ALANIZ, NATALIA LORENA

Mar del Plata

Congreso; Reunión anual de sociedades de biociencias; 2023

Sociedad Argentina de Investigación Clínica

The organophosphates (OPs) are the most widely used pesticides worldwide. In Argentina, the OP chlorpyrifos (CP) was widely utilized until 11/2022. This study aimed to determine the CP level, and key enzymes for OP detoxification, carboxylesterase (CES) and paraoxonase (PON), in the placenta of women residing in the North Patagonia. The study included 104 healthy pregnant women from Neuquén city (CG, n=47) and rural areas (RG, n=57). CP levels were determined by GC-ECD and confirmed by GC-MS. CES activity was determined using α-naphthyl acetate (α-NA) and 4-methylumbelliferyl acetate (4-MUBA) substrates. PON activity was measured using phenylacetate (AE) and dihydrocoumarin (LA) substrates. Transcript and protein levels were assessed by western blot and qPCR. Quantitative and categorical variables underwent Multiple Factor Analysis. CP mean levels (ng/g lipid) in RG (195.9 ± 290.6) were 55% higher than UG (86.3 ± 156.7) (p=0.007, Mann-Whitney), as well as the CP detection frequency (RG: 73% vs UG: 49%). CES activity (α-NA) showed lower levels in RG vs UG (p=0.016, M.W.) while CES (4-MUBA) showed non significant changes (p=0.914, M.W.). Both CES1 and CES2 transcripts were significantly upregulated in RG vs. UG (p=0.010, M.W.), as well as CES 2 protein expression. PON AE and LA activities were higher in RG vs UG (p=0.048, p=0.030, M.W.). PON2 transcript and protein expression levels were increased in RG vs UG (p=0.008, p=0.030 M.W.). Altogether, results indicate that pregnant women are exposed to CP. Low CES activity (α-NA), and the presence of CP was significantly associated with rural areas, making it a valuable indicator for exposure assessment. A compensatory response leading to increased CES1, CES2, PON2 expression and, PON AE and LA activity was also observed in RG. However, augmented CES expressions might not sufficiently counteract the inhibition of CES activity (α-NA). PON induction might be dampening other toxicity mechanisms as oxidative stress.