Dose-Dependent Impact of Ascorbic Acid on Bone marrow Cellularity Against benzene-induced pre-leukemia in Rats

Abstract

Background: Benzene is known to lead to bone marrow failure, oxidative DNA damage (micronucleus formation), pancytopenia, and pre-leukemic changes that can develop into acute myeloid leukemia (AML). Although no specific protective agent is available, vitamin C (ascorbic acid) may attenuate oxidative stress and augment hematopoiesis.

Objective: To assess graded doses of vitamin C versus the benzene-induced effects on the bone marrow and pre-leukemic state in rats.

Materials and Methods: Rats were divided into 6 groups: control, benzene-only or benzene plus vitamin C (100, 200, 500, or 1000 mg/kg/day, oral) for 4 weeks. Pre-leukemia was induced by administration of benzene intravenously (0.2 mL of 1:5:5 benzene:propanol:distilled water) every 48 h; endpoints of bone marrow micronucleus indices (%PCE, %NCE, MN-PCE, MN-NCE, PCE/NCE), CBC with differential, platelet status, inflammatory ratios (e.g., NEU/LYM, SII), and the percent of peripheral blood blast. Results: Benzene induced severe genotoxicity (↓%PCE and PCE/NCE; ↑%NCE, MN-PCE, MN-NCE; p<0.0001), leukopenia (WBC ↓37%) with lymphopenia and monocytopenia, neutrophilia, basophilia, eosinophilia, platelet abnormalities and 35% circulating blasts (0% in control). Vitamin C conferred dose‐dependent protection by increasing the number of markers in the marrow, correcting WBC and differential balance, enhancing platelet count/morphology (MPV, PDW), returning SII elevation to normal, and reducing blasts to 3-4% at 1000 mg/kg.

Conclusions: Vitamin C (100-1000 mg/kg) provides potent, dose-modulated protection of anti-hematotoxic effects and genotoxic properties against benzene, with the highest dose reaching control values and inhibiting pre-leukemic development.