Endoplasmic Reticulum-Targeted Carbon Monoxide Photoreleaser for Drug-Induced Hepatotoxicity Remediation.
Yong LiJiangong ZhangSimiao ChengXu WangJian ZhangXilei XieXiaoyun JiaoBo TangPublished in: Analytical chemistry (2023)
The alleviation of drug-induced liver injury has been a long-term public health concern. Growing evidence suggests that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of drug-induced hepatotoxicity. Therefore, the inhibition of ER stress has gradually become one of the important pathways to alleviate drug-induced liver injury. In this work, we developed an ER-targeted photoreleaser, ERC , for controllable carbon monoxide (CO) release with a near-infrared light trigger. By employing peroxynitrite (ONOO - ) as an imaging biomarker of hepatotoxicity, the remediating effect of CO was mapped upon drug acetaminophen (APAP) challenge. The direct and visual evidence of suppressing oxidative and nitrosative stress by CO was obtained both in living cells and in mice. Additionally, the ER stress inhibiting the effect of CO was verified during drug-induced hepatotoxicity. This work demonstrated that CO may be employed as a potent potential antidote for APAP-related oxidative and nitrative stress remediation.
Keyphrases
- drug induced
- endoplasmic reticulum
- liver injury
- living cells
- public health
- fluorescent probe
- adverse drug
- signaling pathway
- cancer therapy
- high resolution
- single molecule
- metabolic syndrome
- drug delivery
- climate change
- risk assessment
- type diabetes
- stress induced
- anti inflammatory
- skeletal muscle
- electronic health record