Hormetic Dose-Dependent Haematological Effects of n-Hexane Extract of Macadamia integrifolia Nuts in Male Wistar Rats

Abstract

Aims: This study investigated the hormetic dose-response effects of n-hexane extract of Macadamia. integrifolia nuts haematological parameters in male Wistar rats. Study Design: Experimental, controlled, dose–response animal study. Place and Duration of Study: Animal house of the Department of Human Physiology, Rivers State University, Nigeria over a period of 28 days. Methods: Twenty-four (n=24) Male Wistar rats were randomly assigned into four groups (n=6): control (vehicle only), low dose (250 mg/kg), moderate dose (500 mg/kg), and high dose (1000 mg/kg). The extract was administered orally for 28 days. The study was conducted in accordance with institutional ethical guidelines. At the end of the treatment period, blood samples were collected for evaluation of packed cell volume (PCV), haemoglobin (Hb), RBC count, mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), neutrophils, lymphocytes, eosinophils, and monocytes. Results: Low-dose administration produced significant reductions in erythrocyte parameters compared with control, including decreases in PCV (≈11% reduction), Hb (≈13% reduction), and RBC count (≈13% reduction). In contrast, higher doses produced progressive improvements in erythropoietic indices. At 1000 mg/kg, PCV increased by ≈11%, Hb by ≈12%, and RBC count by ≈11% relative to control, alongside increases in MCH and MCV. In addition, the low dose increased total WBC counts by approximately 32% compared with control, accompanied by elevations in neutrophils, lymphocytes, eosinophils, and monocytes. Conversely, the high dose reduced WBC counts by approximately 23% relative to control and normalized leukocyte differentials. Conclusions: n-Hexane extract of Macadamia integrifolia nuts exhibits a clear hormetic dose-response in haematological parameters. Low-dose exposure was associated with suppression of erythrocyte indices and increased leukocyte counts, whereas higher doses enhanced erythropoietic parameters and normalised immune cell profiles. These effects may be linked to phytochemical-mediated modulation of oxidative stress and stimulation of erythropoietic pathways, highlighting the importance of dose optimisation in nutraceutical and pharmacological applications.