Research On Toxicity Of Sterol Oxidation Products In C. Elegans

Sterols, including cholesterol and phytosterols, are unsaturated lipids and prone to oxidation, giving rise to their corresponding cholesterol oxidation products (COPs) and phytosterol oxidation products (POPs). Th formation of sterol oxides is one of the important food safety issues in sterol-rich foods.Previous studies indicated that COPs displayed cytotoxic, atherosclerosis, apoptotic, and pro-inflammatory effects, etc. The different COPs showed different biological effects. However, in the case of phytosterol oxides, research is limit and their biological roles are unclear. Most POPs research reports are focus on the qualitative and quantitative analysis. Therefore, more studies are needed to elucidate the biological effects and their mechanisms, especially at in vivo systems.C. elegans is a multicellular animal that is widely used as biomedical and genetic model organism. Its genome, biosynthetic and metabolic pathways are highly conserved with vertebrates. As an in vivo model, C. elegans provides several characteristics that complement in vitro or cellular modes for exploring sterol functions and compounds’toxicology, such as heavy metals, organic toxins, and drugs, etc. Transparency of the animals allows the evaluation of potential toxins on cellular morphology. Cells can be observed using fluorescent microscopy or differential interference contrast (DIC) optics.While the biological effects of sterols have been well studied on C.elegans, the amount of biological research on sterol oxides is scarce. Therefore, using the nematode C. elegans as model organism, the in vivo toxicity of sterol oxides,7-ketocholesterol,7-ketocampesterol and 7-ketositosterol, are investigated. The experimental results are as follows:1. At the concentration 5 μg/mL, sterol oxides could substitute for cholesterol in the growth of C. elegans.7-Ketocholesterol shows weak effects on worms’ reproductive ability, while 7-ketositosterol and 7-ketocampesterol did not display this potency. Three sterol oxides produced significant difference in worms’ body size, however, showed no significant effect in lifespan and pharyngeal pumping rates on C. elegans compared to the controls.2. When C. elegans were exposured to 7-ketocholesterol at concentrations ranging from 0 to 200 μg/mL, their acute effects on lethality, long-term effects on the lifespan, short-term effects on reproduction, thermotolerance, germ line apoptosis, as well as reactive oxygen species (ROS) were studied. The results indicated 7-ketocholesterol reduced reproductive capacity, shortened the life span in a concentration-dependent manner, and impaired thermotolerance of the adult nematode.7-Ketocholesterol also induced germline apoptotic cell death and increased ROS generation in adult worms.Our findings are relevant with a view to determinging the safety of sterol oxides, and it indicated that the in vivo model organism. C. elegans, can make us better understand the safety and bioactivity of sterol oxides.