Arachidonic Acid and Lipoxin A4 Protect Pancreatic β-Cells and Improve Hyperglycemia Induced by Bleomycin

This study was conducted to examine whether bleomycin-induced growth inhibitory action on rat insulinoma cells (RIN5F) in vitro and hyperglycemia in female Wistar rats is influenced by arachidonic acid (AA) and its anti-inflammatory metabolite: lipoxin A4 (LXA4). The in vitro study was conducted using RIN5F cells. The potential of various PUFAs (polyunsaturated fatty acids), eicosanoids and LXA4, resolvin D1 and protectin D1 to modify the growth inhibitory effects of bleomycin was measured by MTT assay. In an in vivo study, we tested the effect of AA and LXA4 on bleomycin-induced hyperglycemia in female Wistar rats. We noted that of all the PUFAs and their metabolites tested, AA (10 µg/mL) and LXA4 (1 ng/mL) are the most effective in protecting RIN5F cells against bleomycin induced growth suppression. An increase in LXA4 levels was noted when RIN5F cells were supplemented with AA. Bleomycin induced a significant increase in the fasting blood glucose levels and decreased plasma insulin levels that were reverted to normal by LXA4 (50 ng/animal). AA (50 μg/animal) and LXA4 improved the antioxidant status and upregulated anti-inflammatory and anti-apoptotic genes IκB and Bcl2. These results suggest AA and LXA4 can prevent bleomycin-induced dysfunction of pancreatic β cells.