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This study aims to explore the immunotoxicity and metabolic mechanisms of hexavalent chromium in rabbit spleen tissues.

June 20, 2026Open Access

Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits

Key Points

This study aims to explore the immunotoxicity and metabolic mechanisms of hexavalent chromium in rabbit spleen tissues.
New Zealand rabbits were exposed to varying doses of hexavalent chromium (0, 12.5, 25, 50 mg/L) via drinking water for four weeks.
Spleen injury was assessed using hematoxylin and eosin staining, immunohistochemistry, and ELISA for antioxidant levels.
Gene expression was analyzed via qRT-PCR and iron accumulation was detected through enhanced Prussian blue staining.
High-dose Cr(VI) decreased body weight gain and caused lymphocyte atrophy and spleen damage.
Cr(VI) exposure led to reduced T and B lymphocyte populations, increased macrophage infiltration, and elevated inflammatory cytokine expression.
Ferroptosis was triggered through lipid peroxidation and GPX4 downregulation, alongside increased iron accumulation.

Abstract

Background: Hexavalent chromium (Cr(VI)) is a widespread environmental toxic heavy metal with strong oxidative properties; however, its immunotoxicity and metabolic mechanisms in rabbit spleen remain largely unclear. Methods: In this study, New Zealand rabbits were exposed to 0, 12.5, 25, and 50 mg/L Cr(VI) (as potassium dichromate, K2Cr2O7) via drinking water for four weeks to investigate splenic damage and the underlying molecular pathways. Spleen pathological injury was evaluated by hematoxylin and eosin (H&E) staining, and the distribution of T cells, B cells, and macrophages was assessed by immunohistochemistry. Antioxidant enzyme activities and antioxidant substance levels were determined using ELISA, and the relative mRNA expression of immune factor genes, antioxidant-related genes, and ferroptosis-related genes was quantified by quantitative real-time PCR (qRT-PCR). In addition, the distribution of iron in splenic tissue was detected by enhanced Prussian blue staining. Results: Our results demonstrate that high-dose Cr(VI) significantly inhibited body weight gain, induced lymphocyte atrophy, vacuolization, and widening of intercellular spaces in the splenic white pulp. Furthermore, Cr(VI) reduced T and B lymphocyte populations, promoted macrophage infiltration and inflammatory cytokine gene expression in a concentration-dependent manner, impaired total antioxidant capacity, and led to a decrease in glutathione (GSH) levels in the spleen. Additionally, Cr(VI) exposure increased iron accumulation, activated the ACSL4–NOX lipid peroxidation cascade, and downregulated GPX4 expression, ultimately triggering ferroptosis. Conclusions: These findings reveal that Cr(VI) causes splenic immune injury by disrupting oxidative homeostasis and inducing ferroptosis, providing novel insights for evaluating immunotoxicity and identifying metabolic targets under Cr(VI) pollution.

Metabolic Mechanisms of Hexavalent Chromium-Induced Splenic Immune Injury via Oxidative Stress and Ferroptosis Pathways in New Zealand Rabbits

Key Points

Abstract

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