Abstract
Astaxanthin is a natural food factor found in algae, fish, and birds. It is a powerful antioxidant and has various actions such as anti-inflammation, anti-hypertension, and anti-diabetic nephropathy. Recent advances in the disease prevention and health promotion of astaxanthin was reviewed by our publication. Chronic treatment with astaxanthin protected β-cells against glucose toxicity as well as ameliorated the progression and acceleration of diabetic nephropathy in the mouse model of type 2 diabetes. The increases in urinary 8-OHdG, an oxidative DNA damage marker, and 8-OHdG immunoreactive cells in the glomeruli of the diabetic mice aged 12 weeks were significantly inhibited by astaxanthin. DNA microarray analysis demonstrated that the affected genes were associated with complexes I, III, and IV located on the mitochondrial inner membrane, and the expression levels of these genes were decreased in mice treated with astaxanthin as compared to the levels in the control mice. In vitro study using human mesangial cells has showed that astaxanthin significantly suppressed high glucose-induced reactive oxygen species production, the activation of transcription factors, and cytokine expression/production by mesangial cells. In addition, astaxanthin accumulated in the mitochondria of cells and reduced the production of 4-hydroxy-2-nonenal modified proteins in the mitochondria. In addition, we found that astaxanthin improved oxidative muscle damage and muscle lipid metabolism in exercise via its inhibitory effect on oxidative carnitine parmitoyltransferase I (CPT I) modification. CPT I located on the mitochondria membrane plays an important role in the entry of fatty acids. These data may indicate that reactive oxygen species generated from mitochondria during several pathological conditions regulate the down-stream signal transduction, and that the beneficial effects of astaxanthin might be derived from the modulation of mitochondrial function.
