Abstract: Objective: This study investigated the alleviating effect of chlorophyll on Cd-induced liver and kidney damage in mice and explored its potential mechanisms. Methods: Male C57BL/6J mice were exposed to 100 mg/L CdCl2 via drinking water for 8 consecutive weeks to establish a cadmium exposure model. High-dose (0.09 mg/g) and low-dose (0.045 mg/g) chlorophyll were added to the diet. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities, as well as urea, uric acid (UA), and creatinine (CREA) levels were measured. In addition, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in liver and kidney tissues were determined. Lastly, the alleviating effect of chlorophyll on cadmium-induced liver and kidney injury in mice was elucidated through hematoxylin and eosin (HE) staining, transcriptomics, and non-targeted metabolomic analysis. Results: Compared with the Cd group (100 mg/L CdCl2 solution), chlorophyll intervention improved hepatic antioxidant defense, as evidenced by increased SOD and GSH-Px activities and decreased MDA levels. Meanwhile, the serum levels of AST, urea, and CREA were significantly reduced (P < 0.05), and histopathological lesions such as hepatocellular hydropic degeneration and glomerular atrophy were alleviated. Metabolomics identified 52 differential metabolites in the liver and 49 in the kidney. These metabolites were primarily involved in glycerophospholipid, linoleic acid, and phenylalanine metabolic pathways. Transcriptomics identified 799 differential genes in the liver and 1 778 in the kidney. These genes were enriched in oxidative phosphorylation, phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), and lipid metabolism pathways. Collectively, chlorophyll significantly alleviates cadmium-induced oxidative damage in the liver and kidney by mitigating mitochondrial DNA damage, regulating energy metabolism, and restoring lipid and amino acid metabolic homeostasis. Conclusion: Chlorophyll from purple laver exhibits potent antioxidant and detoxifying effects, positioning it as a potential dietary functional factor for controlling cadmium toxicity. This provides a scientific rationale for nutritional intervention in populations exposed to high cadmium levels.

Key words: cadmium; chlorophylls; untargeted metabolomics; transcriptomics; oxidative damage