Acetaminophen (APAP) is a widely used antipyretic and analgesic agent, and acute exposure can lead to renal injury. Sesamin (Ses) is known for its various health benefits. However, it remains unclear whether Ses exerts a protective effect against APAP-induced kidney injury. In vivo, C57BL/6 mice were pretreated with Ses and injected intraperitoneally with APAP. In vitro, human kidney proximal tubule cells 2 were pretreated with Ses, and then models of kidney injury induced by APAP were established. Kidney damage was evaluated by morphological, inflammation, oxidative stress and protein analyzes. Ses significantly improved APAP-induced nephrotoxicity in vitro and in vivo models. Transcriptomic analysis revealed that the differentially expressed genes were enriched in ferroptosis and apoptosis signaling pathways, identifying heme oxygenase 1 (HMOX1) as a core protein. In the Ses-treated group, ferroptosis and apoptosis were significantly inhibited, while HMOX1 was effectively restored. In cell experiments, both the HMOX1 agonist hemin and Ses attenuated ferroptosis and apoptosis. HMOX1 inhibitor Zinc Protoporphyrin significantly eliminated the protective effect of Ses. Ses alleviates APAP-induced renal injury by mediating the inhibition of ferroptosis and apoptosis via HMOX1. This study provides a new strategy for the prevention and treatment of drug-induced renal injury.

Acetaminophen (APAP) is a widely used antipyretic and analgesic agent, and acute exposure can lead to renal injury. Sesamin (Ses) is known for its various health benefits. However, it remains unclear whether Ses exerts a protective effect against APAP-induced kidney injury. In vivo, C57BL/6 mice were pretreated with Ses and injected intraperitoneally with APAP. In vitro, human kidney proximal tubule cells 2 were pretreated with Ses, and then models of kidney injury induced by APAP were established. Kidney damage was evaluated by morphological, inflammation, oxidative stress and protein analyzes. Ses significantly improved APAP-induced nephrotoxicity in vitro and in vivo models. Transcriptomic analysis revealed that the differentially expressed genes were enriched in ferroptosis and apoptosis signaling pathways, identifying heme oxygenase 1 (HMOX1) as a core protein. In the Ses-treated group, ferroptosis and apoptosis were significantly inhibited, while HMOX1 was effectively restored. In cell experiments, both the HMOX1 agonist hemin and Ses attenuated ferroptosis and apoptosis. HMOX1 inhibitor Zinc Protoporphyrin significantly eliminated the protective effect of Ses. Ses alleviates APAP-induced renal injury by mediating the inhibition of ferroptosis and apoptosis via HMOX1. This study provides a new strategy for the prevention and treatment of drug-induced renal injury.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Inorganic Crystal Structure Database, the world’s repository for inorganic crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the joint CCDC and FIZ Karlsruhe Access Structures service and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.