Cold atmospheric plasma-derived ROS detoxifies deoxynivalenol-induced nephrotoxicity

Deoxynivalenol (DON) widely contaminates cereals, causing severe kidney damage in human and animal. However, its underlying mechanisms and efficient detoxification strategy is still limited. Cold atmospheric plasma (CAP) containing rich reactive oxygen species is regarded as an emerging approach for mycotoxin decontamination in cereals. Here we focus on the potential mitigating role CAP in DON-induced nephrotoxicity by exploring DON degradation pathways, toxicity mitigation, and cellular recovery. The results show that CAP-derived ¹O₂, ∙OH, ∙O₂^-, and H₂O₂ degraded over 98 % of DON after 120-s treatment and destroyed the toxic epoxy, double bond and hydroxyl group of DON to generate 5 degradation products. The toxicity test was conducted using human renal proximal tubular epithelial cells (HKC-8) in-vitro and murine acute kidney injury model in-vivo. The mechanistic insights into oxidative stress and apoptosis pathways, including Nrf2/HO-1/NQO-1 signaling and JNK-mediated Nrf2 degradation were explored. DON caused serious nephrotoxicity in-vitro and mice by inducing mitochondrial oxidative damage and cell apoptosis via activating Nrf2 phosphorylation and sequentially inhibiting Nrf2/HO-1/NQO-1 signaling pathway, resulting in 45 % loss of HKC-8 cell viability, 85 % of elevation in serum creatinine, and 89 % of increase in blood urea nitrogen (BUN) levels compared with control. While, CAP-treated DON (Pla-DON) can reverse the mitochondrial damage and maintain intracellular redox homeostasis via blocking JNK-mediated Nrf2 degradation, rescuing 50 % of HKC-8 cell activity and reducing creatinine and BUN by 89 % and 83 % compared with DON group. Overall, this study demonstrates the considerable potential of CAP to mitigate DON-induced nephrotoxicity.