A zingiberene-selenium nanoparticle formulation modulates oxidative, inflammatory, and osteogenic responses during femoral fracture healing in rats.

INTRODUCTION

Bone fracture healing involves coordinated inflammatory, oxidative, and remodeling processes. This study evaluated free zingiberene and a zingiberene-selenium nanoparticle (zingiberene-SeNP) formulation in a rat femoral fracture model.

METHODS

Twenty-four adult male Wistar rats were assigned to intact control, fracture control, fracture plus zingiberene (10 mg/kg/day), or fracture plus zingiberene-SeNP formulation (0.5 mg/kg/day, expressed as total administered formulation mass) groups for 35 days. Outcomes included serum calcium, phosphate, magnesium, and alkaline phosphatase (ALP); malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT); C-reactive protein (CRP), cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB); C-terminal telopeptide of type I collagen (CTX-I), calcitonin, osteocalcin, osteoprotegerin (OPG), and bone morphogenetic protein-1 (BMP-1), together with radiographic and hematoxylin and eosin (H&E) histology.

RESULTS

Fracture disrupted mineral, oxidative, inflammatory, and bone-turnover profiles. Both treatments improved multiple biochemical and inflammatory indices versus fracture control. The zingiberene-SeNP formulation showed stronger effects than free zingiberene for selected endpoints, including MDA, GSH, ALP, PGE₂, TNF-α, IL-1β, NF-κB, CTX-I, calcitonin, osteocalcin, OPG, and BMP-1. Radiographic and histological findings were consistent with improved callus organization and bone maturation.

DISCUSSION: Overall, both treatments favorably modulated fracture-repair responses, with greater effects of the nanoformulation for selected parameters.