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Protective Effects of Cordycepin against Oxaliplatin-Associated Drug-Induced Fatty Liver Disease and Preliminary Mechanistic Insights

ABSTRACT:

Oxaliplatin (OXA) is a chemotherapeutic agent used to treat multiple malignancies. Although it predominantly causes hepatic sinusoidal obstruction syndrome, it also induces drug-induced fatty liver disease (DIFLD) via lipid metabolic dysregulation and oxidative stress, which persists post-cessation, impairing long-term prognosis. Therefore, precise histopathological classification and targeted hepatoprotective interventions are crucial. Currently, no well-established preventive or therapeutic strategies for OXA-associated DIFLD exist. Cordycepin, a natural compound with established antihyperlipidemic and antioxidant properties, has not been studied for its protective effects against OXA-induced DIFLD. This study aimed to establish an acute OXA-induced DIFLD mouse model and evaluate the protective effects and underlying mechanisms of cordycepin intervention against OXA-induced DIFLD. An acute OXA-induced DIFLD model was established by administering 8 mg/kg OXA intraperitoneally daily for 3 days. Hepatic histopathology was assessed using hematoxylin and eosin and oil red O staining. Serum alanine aminotransferase, aspartate aminotransferase, hepatic and serum lipids (triglycerides, total cholesterol, and low-density lipoprotein, and oxidative stress markers (superoxide dismutase, malondialdehyde, and glutathione peroxidase were also measured. Non-targeted metabolomics and data-independent acquisition-based proteomics identified differential metabolites and proteins, followed by bioinformatic analysis. OXA significantly induced hepatic injury, steatosis, and oxidative stress, all of which were markedly attenuated by cordycepin treatment. Integrative metabolomic and proteomic analyses revealed that cordycepin modulated arginine biosynthesis and bile secretion pathways, downregulated oxoglutaric acid, and alleviated hepatotoxicity by regulating lipid metabolism and mitigating oxidative stress. This study demonstrated the efficacy of cordycepin against OXA-induced DIFLD and elucidated its underlying mechanisms, offering a novel therapeutic strategy and scientific basis for the precise management of OXA-associated hepatic injury.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12938 | MetaboLights | 2025-09-04

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12938_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12938_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12938_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS12938_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Protective Effects of Cordycepin against Oxaliplatin-Associated Drug-Induced Fatty Liver Disease and Preliminary Mechanistic Insights

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