Lycopene supplementation during pregnancy and lactation attenuates thermally oxidized cooking oil-induced hepatic and cerebral damage in rat offspring: A comprehensive histomorphometric and molecular analysis.

Background: Thermally oxidized cooking oil (TOCO) generates reactive oxygen species and lipid peroxidation products that cross the placental barrier, posing risks to offspring organ development in low-to-middle income countries where cooking oil reuse is endemic. Lycopene, a potent carotenoid antioxidant, possesses neuroprotective and hepatoprotective properties, yet its capacity to prevent maternal-to-offspring oxidative damage through maternal supplementation remains unexplored. Methods: Twenty-four female Sprague Dawley rats were randomized into six groups (n = 4 dams each): Control, CMC vehicle, TOCO1 × , TOCO3 × , TOCO1 × + Lycopene, and TOCO3 × + Lycopene. Lycopene (0.24 mg/kg) was administered via oral gavage from gestational day 1 through postnatal day 14 (total duration: 35 days encompassing pregnancy and early lactation). Dam was used as the experimental unit for all inferential statistics to avoid pseudo-replication. Statistical analysis employed Kruskal-Wallis and Mann-Whitney U tests with Benjamini-Hochberg FDR correction, effect size estimation (Cohen's d with 95% CI), and post-hoc power analysis. Results: TOCO3 × exposure significantly reduced normal hippocampal CA1 neurons (60% vs 85% controls; Cohen's d=2.2, p < 0.05), cerebellar Purkinje cells (55% vs 90%; d=2.5, p < 0.05), and increased hepatocyte damage (27% vs 8%; d=2.8, p < 0.05). Lycopene supplementation provided substantial protection: hippocampal recovery to 75% (PI 60%), cerebellar recovery to 78% (PI 66%), liver recovery to 15% damaged (PI 63%), with NNT of 4-5. Biochemical markers (MDA, GSH) showed non-significant trends (post-hoc power 15-42%). Caspase-3 expression showed dose-dependent elevation with TOCO and suppression with lycopene. Conclusions: Maternal lycopene supplementation provides significant multi-organ protection against TOCO-induced developmental toxicity. These findings are supported by convergent evidence from histopathology (d=2.2-2.8), molecular markers (caspase-3 dose-response), and exposure characterization, consistent with oxidative stress-mediated mechanisms. The translational HED (2.7 mg/day from 150 g fresh tomatoes) supports investigation of dietary lycopene as a public health intervention for pregnant women in TOCO-endemic populations.