# Docosahexaenoic Acid Increases the Pro-Resolving Brain Lipid Mediators of Inflammation in Rat Pups Prenatally Exposed to Alcohol

## TL;DR

This study shows that DHA can boost brain anti-inflammatory molecules in rat pups exposed to alcohol during pregnancy, potentially reducing FASD risks.

## Contribution

The study demonstrates DHA's ability to increase pro-resolving lipid mediators in alcohol-exposed fetal brains.

## Key findings

- High-dose alcohol significantly reduced both pro-inflammatory and pro-resolving lipid mediators in rat pups.
- DHA supplementation with high-dose alcohol increased pro-resolving lipid mediators like LXA5, MaR1n-3 DPA, and 17-HDoHE.
- 4-HDoHE levels tripled in the DHA-supplemented alcohol-exposed group.

## Abstract

Fetal alcohol spectrum disorder (FASD/FAS) is a chronic inflammatory process of the fetal brain induced by alcohol and mediated by pro-inflammatory (PILM) and pro-resolving (PRLM) lipid mediators of inflammation. DHA (docosahexaenoic acid) is an essential precursor of PRLM. A study examining the response of lipid mediators of inflammation to alcohol insult and DHA supplementation can provide vital information on the pathogenesis of FASD/FAS and the potential ameliorative role of DHA. Four groups of timed pregnant rats were studied: control, low-dose (1.6 g/kg/day) and high-dose (2.4 g/kg/day) alcohol, and high-dose alcohol (2.4 g/kg/day) + DHA (1250 mg/kg/day). The pups were delivered on day 20, and their whole brain was examined for lipid mediators by liquid chromatography mass spectroscopy. The following biomarkers of brain lipid mediators were studied, namely, PILM (LTB4, PGE2, PGF2α, TXB2) and PRLM (LXA5, 4-HDoHE, 17-HDoHE, and MaR1n-3, DPA). The brain PILM and PRLM concentrations decreased significantly (p < 0.001) with high-dose alcohol. However, high-dose alcohol + DHA resulted in a significant (p < 0.001) increase in PRLM levels, viz., LXA5, MaR1n-3 DPA, 17-HDoHE, and a threefold increase in 4-HDoHE. We conclude that DHA supplementation in alcohol-exposed pregnant rats significantly increased levels of brain pro-resolving lipid mediators in the offspring, suggesting a potential role in modulating the inflammatory response.