Sodium nitroprusside alleviates nanoplastics-induced developmental toxicity by suppressing apoptosis, ferroptosis and inflammation.

ABSTRACT

The health damage caused by nanoplastics (NPs) pollution has become one of the global scientific problems to be solved urgently. However, the toxicological mechanism of NPs is complex, and the research progress of anti-toxicity is limited. Thus, it has potential application value to explore or develop drugs that can effectively alleviate or remove NPs with biological toxicity. In this research, 8 µM sodium nitroprusside (SNP) solution was used to treat zebrafish larvae with 20 mg/L NPs for up to 12 days, and the results showed that SNP treatments were effective in alleviating NPs-caused developmental toxicity in zebrafish larvae. Further examination of its signaling pathway revealed that NPs-induced oxidative stress was mitigated by activating the NO-sGC-cGMP signaling pathway and reduced most of the reactive oxygen species (ROS). Subsequently, we detected the key substances and the key enzymes involved in apoptosis and ferroptosis, and found that oxidative stress-induced mitochondria-dependent apoptosis and lipid peroxidation-caused ferroptosis were alleviated. Finally, observed the accumulation of NPs and ROS in the liver of zebrafish larvae, which is the target organ of immunotoxicity, and we found that SNP could alleviate NPs-caused inflammation by analyzing the fluorescence intensity of neutrophils and macrophages in transgenic zebrafish and detecting the expression of key immune genes. In conclusion, this research has shown for the first time that SNP treatment can significantly inhibit NPs-induced developmental toxicity, resulting from oxidative stress-induced apoptosis, ferroptosis and inflammation in zebrafish larvae.