Passiflora edulis Seed Oil in an Experimental Zebrafish Model of Hyperglycemia During Embryogenesis: Evaluation of Free Glucose Modulation, Oxidative Stress, Antioxidant Gene Expression, and Developmental Safety.

Passiflora edulis seed oil (PESO) is a rich source of lipophilic bioactive compounds with potential to modulate oxidative stress and free glucose levels. This preclinical study aimed to evaluate the toxicological profile, antioxidant and glucose-modulating effects of PESO using hyperglycemic Danio rerio embryos (AB strain). PESO was chemically characterized by GC-FID/GC-MS after derivatization to fatty acid methyl esters. In animal studies, the median lethal concentration (LC50) of PESO at 96 h post-exposure (hpe) was determined using concentrations ranging from 12.5 to 400 μg/mL, and sublethal concentrations corresponding to 1/10 and 1/20 of the LC50 were selected for further investigations, including survival rate up to 144 hpe, continuous and pulsatile hyperglycemia assays (total free glucose was quantified in washed embryo or larval homogenates using an Accu-Chek Active® glucometer) (Roche Diabetes Care GmbH, Mannheim, Germany), total reactive oxygen species (ROS) production, and antioxidant gene expression at 96 hpe. Data were analyzed by nonlinear regression or analysis of variance followed by appropriate post hoc tests, with significance set at p ≤ 0.05. Chemical characterization identified linoleic acid (C18:2) as the predominant fatty acid. PESO exhibited an LC50 of 191.1 µg/mL. PESO at 9.5 and 19.1 µg/mL achieved embryonic survival above 85% and reduced total free glucose values in washed embryo or larval homogenates under pulsatile and continuous hyperglycemic conditions (p ≤ 0.05), although less effective than insulin (0.1 U/mL). PESO attenuated ROS production by 2% (w/v) glucose (p ≤ 0.05). PESO treatment was associated with distinct concentration-related expression profiles among the selected antioxidant-related genes: sod1 and cat expression increased at both concentrations, sod2, gpx1a, and gsr increased at 19.1 µg/mL, and nfe2l2a increased at 9.5 µg/mL (p ≤ 0.05). At the selected sublethal concentrations, PESO showed low embryotoxicity and was associated with reduced total free glucose values, partial attenuation of ROS accumulation, and changes in selected antioxidant-related transcripts in embryos exposed to hyperglycemic conditions.