Exposome-Induced Oxidative Stress and Protective Effects of Antioxidants in Rats

The exposome can be defined as the totality of exposures (diet, lifestyle, occupational, and environmental factors) received by an individual throughout the entire lifetime. It is unclear how these exposures are related to health. There is an increasing trend to intake food additives due to food mileage extension and maintenance of a healthy lifestyle. Therefore, we investigated the effect of aspartame (APM), an artificial sweetener, and ortho-phenyl phenol (OPP), a broad-spectrum fungicide and antibacterial agent, on oxidative stress in rats. APM (250 mg/kg/day; 1/16 NOAEL) or OPP (1 &#u181;g/kg/day; 1/105 NOAEL) were administered to rats for &#~8776;eight weeks, through their mixed diet and drinking water, respectively. Administration of both exposomes for two weeks led to a significant reduction in reactive oxygen specie (ROS)-scavenging ability for hydroxyl radicals in plasma. In epididymis and hippocampus, both exposome treatments increased the 4-hydroxy-2-nonenal (HNE) levels, an index of lipid peroxidation. APM treatment for two weeks increased ROS generation in sperms without motility changes. Moreover, APM treatment for eight weeks slightly decreased sperm motility. Furthermore, amyloid beta (Abeta) levels were significantly increased in both epididymis and hippocampus after two weeks of OPP administration, that may be related to male infertility and dementia. Pretreatment with the antioxidant Twendee X (20 mg/kg/day; TIMA Japan) inhibited the Abeta level increase in both tissues. In conclusion, our data indicate that some exposomes systemically induce oxidative stress and increase Abeta levels in both epididymis and hippocampus. These results suggested that effective antioxidants such as Twendee X can inhibit exposome-induced oxidative stress in male infertility and neurodegenerative diseases.