Radiation is pro-inflammatory in nature in view of its ability to induce the generation of reactive oxygen species (ROS), cytokines, chemokines, and growth factors with associated inflammatory cells. Cells are efficient in repairing radiation-induced DNA damage; however, exactly how this happens is not clear. In the present study, GLA reduced DNA damage (as evidenced by micronuclei formation) and enhanced metabolic viability, which led to an increase in the number of surviving RAW 264.7 cells in vitro by reducing ROS generation, and restoring the activities of desaturases, COX-1, COX-2, and 5-LOX enzymes, TNF-α/TGF-β, NF-kB/IkB, and Bcl-2/Bax ratios, and iNOS, AIM-2, and caspases 1 and 3, to near normal. These in vitro beneficial actions were confirmed by in vivo studies, which revealed that the survival of female C57BL/6J mice exposed to lethal radiation (survival~20%) is significantly enhanced (to ~80%) by GLA treatment by restoring altered levels of duodenal HMGB1, IL-6, TNF-α, and IL-10 concentrations, as well as the expression of NF-kB, IkB, Bcl-2, Bax, delta-6-desaturase, COX-2, and 5-LOX genes, and pro- and anti-oxidant enzymes (SOD, catalase, glutathione), to near normal. These in vitro and in vivo studies suggest that GLA protects cells/tissues from lethal doses of radiation by producing appropriate changes in inflammation and its resolution in a timely fashion.

Our previous studies revealed that certain endogenous low molecular weight lipids have potent anti-diabetic actions. Of all, arachidonic acid (AA) and its anti-inflammatory and inflammation resolving metabolite lipoxin A4 (LXA4) are the most potent anti-diabetic molecules. Similar anti-diabetic action is also shown by resolvins. In our efforts to identify other similar lipid based anti-diabetic molecules, we investigated potential anti-diabetic action of protectin DX that also has anti-inflammatory and inducer of inflammation resolution action(s) like LXA4. Protectin DX {10(S),17(S)-dihydroxy-4Z,7Z,11E,13Z,15E,19Z-docosahexaenoic acid, also called as 10(S),17(S)-DiHDoHE)} prevented the development of streptozotocin-induced type 1 and type 2 diabetes mellitus in Swiss male albino mice. Protectin DX showed potent anti-inflammatory, antioxidant and anti-apoptotic actions that could explain its anti-diabetic action. In view of these beneficial actions, efforts need to be developed to exploit PDX and other similar compounds as potential anti-diabetic molecule in humans.

Metabolism of EFAs EFAs are polyunsaturated fatty acids (PUFAs) since they contain two or more double bonds.