Bovine Milk Exosomes as Natural Cytoprotective Nanoplatforms Against Lead-Induced Toxicity.

PURPOSE: Exosomes derived from mammalian milk are extracellular vesicular dietary agents capable of interspecies communication. Bovine milk exosomes (BMEs) are abundant natural nanovesicular resources that are enriched in bioactive components, including proteins, lipids, and microRNAs, and as such possess tremendous potential to affect cellular functions in the consumers. Although the applications of BMEs as delivery platforms for exogenous therapeutics are well known, their endogenous therapeutic potential remains relatively undiscerned. This study aimed to examine the cytoprotective role of BMEs as stand-alone therapeutic agents on human embryonic kidney (HEK293T) cells exposed to a prevalent environmental toxicant, lead (Pb). METHODS: Isolation of BMEs was performed using standardized ultracentrifugation-based protocols. The physico-biochemical characterization of BMEs was performed using electron microscopy, Western blotting and dynamic light scattering (DLS). The ameliorative effects of BMEs were evaluated using spectrophotometric assays for cellular viability/toxicity and oxidative stress. RESULTS: Our results confirmed that Pb is a potent cytotoxic chemical, the exposure of which was associated with significant decreases in cellular viabilities in MTT reduction and lactate dehydrogenase (LDH) release assays. Additionally, Pb treatment increased the formation of reactive oxygen (ROS) and nitrogen (RNS) species. However, cotreatment with BMEs significantly mitigated Pb-induced oxidative stress and cellular damage. CONCLUSION: This study highlights the endogenous potential of BMEs as therapeutic and biotechnological agents against chemical toxicity.