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Perillyl alcohol-induced hematological modulations: insights into human blood cells damage, eryptosis, and systemic perturbations

Year: 2026

Type: article

Abstract: Perillyl alcohol (POH) is a natural monoterpene with established antitumor activity. Although its anticancer efficacy is well-documented, its impact on normal blood cells, particularly red blood cells (RBCs), remains underexplored. Given the importance of RBC integrity in maintaining homeostasis, this study aims to investigate the hematological effects of POH, focusing on hemolysis, eryptosis, and systemic blood parameters. Erythrocytes collected from June-August 2023 were treated with POH (0.5–2.5 mM) for 24 hr at 37°C. Hemolysis was assessed using photometric assays. Eryptosis was detected by flow cytometry using annexin V, Fluo4/AM, and H2DCFDA to quantify phosphatidylserine (PS) translocation, intracellular Ca2+, and oxidative stress, respectively. Complete blood count (CBC) parameters were also analyzed. POH induced dose-dependent hemolysis, elevated intracellular Ca2+, and significant PS externalization, indicating increased eryptosis. The hemolytic activity of POH was supported by marked increases in LDH, CK, and AST. Notably, polyethylene glycol (PEG) significantly attenuated hemolysis, suggesting a protective effect. In whole blood, POH reduced RBC count, hemoglobin, and hematocrit, while increasing RDW-CV. Reticulocyte profiling showed elevated immature reticulocyte fraction (IRF) and a medium fluorescence ratio (MFR). Moreover, POH induced leukopenia with immature granulocytes and platelet aggregation. POH disrupts RBC integrity, triggering hemolysis and eryptosis independently of oxidative stress. The observed hematological alterations underscore potential systemic toxicity and highlight the need for further preclinical evaluation to guide its therapeutic use in oncology.

Source: The Journal of Toxicological Sciences

DOI: 10.2131/jts.51.45

Authors: Ahmed M. Basudan, Jawaher Alsughayyir, Yazeed A. Al-Sheikh, Mohammad A. Alfhili

Institution: King Saud University

Language: English

Topic: Erythrocyte Function and Pathophysiology

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: King Saud University