Carnosic acid attenuates acrylamide-induced retinal toxicity in zebrafish embryos.

Acrylamide (ACR) is a water-soluble chemical used widely in industry, which can be formed in tobacco smoke and in starchy foods cooked at high temperatures. ACR is considered to be a neurotoxin, genotoxin and carcinotoxin. Previous studies reported that ACR-exposed workers and experimental animals exhibited visual function defects, although the underlying mechanisms have not been elucidated. In this study, we found that zebrafish embryos exposed to 1 mM and 2 mM ACR showed significantly increased reactive oxygen species (ROS), decreased expression of the antioxidant genes Sod1, Sod2, Catalase, Gpx1 and Nrf2, reduced activity of superoxide dismutase (SOD) and catalase, and elevated malondialdehyde (MDA), compared with control embryos. ACR exposure caused loss of both rod and cone photoreceptor cells through Caspase-3-dependent apoptotis. When embryos were simultaneously exposed to ACR and the natural antioxidative substance carnosic acid (CA), the presence of the latter (10 µM) markedly counteracted the above ACR-induced toxic effects. Our data suggest that CA can protect photoreceptor cells against ACR-induced oxidative damage and has a potential for neuroprotection of visual function in humans exposed to ACR.

Protective effect of carnosic acid against acrylamide-induced toxicity in RPE cells.

Acrylamide is a substance that can be neurotoxic in humans and experimental animals. It is formed at different rates in starchy foods cooked at temperatures above 120 °C as a result of interaction between monosaccharides and the amino acid asparagine. Carnosic acid accounts for over 90% of the antioxidant properties of rosemary extract and is a powerful inhibitor of lipid peroxidation in microsomal and liposomal systems. Carnosic acid has been shown to protect against oxidative and inflammatory effects. In order to investigate the protective properties of carnosic acid against acrylamide-induced toxicity in human retinal pigment epithelium (RPE) cells, ARPE-19 cells were pre-treated with 10 µM carnosic acid for 24 h followed by treatment with acrylamide (0.7 or 1 mM) for 24 h. ARPE-19 cells pre-treated with 10 µM carnosic acid showed significantly increased cell viability and decreased cell death rate when compared to ARPE-19 cells treated with acrylamide alone. Activities of SOD and catalase and the level of GSH and expression of NRF2 and a number of anti-oxidant genes were significantly decreased in ARPE-19 cells, while there were significant increases in ROS and MDA; pre-treatment with carnosic acid significantly counteracted these changes. Our results suggest that carnosic acid protected RPE cells from acrylamide-induced toxicity.