The effects of mango ginger on osteoclastogenesis and bone damage induced by acute methotrexate chemotherapy in rats

Methotrexate (MTX), a folic acid antagonist, causes bone defects in the form of low mineral density (BMD) and bone fractures. Mango ginger (MG) has anti-inflammatory and antioxidant properties. The purpose of the present study was to investigate the potential protective role of MG administration and its mechanisms against MTX induced bone damage in rats. A total of 28 Sprague-Dawley male rats were randomly allocated into four groups as follows; i) control; ii) MG group, rats were treated orally with 50 mg/kg/day of MG for 15 days, iii) MTX group, rats were injected subcutaneously with 0.75 mg/kg of MTX on 8th and 12th days for 5 days, and iv) MTX+MG group, rats were treated orally with 50 mg/kg/day of MG for 15 days and injected with MTX on 8th and 12th days for 5 days. MTX significantly increased serum aminotransferase enzyme activities and urea creatinine levels, while osteocalcin levels and tibia and femur BMD decreased (P < 0.001; for all). MG pretreatment markedly attenuated aminotransferases activities and creatinine levels and increased tibia osteocalcin levels and femur BMD in the MTX + MG groups. There was no difference in serum glucose and cholesterol levels among all groups. MTX increased bone nuclear factor kappa beta ligand receptor-activator (RANKL), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels and decreased the bone osteoprotegerin (OPG) and type1 collagen levels (P < 0.001). The effect of MG treatment on RANKL, IL-6, TNF-α, OPG and type1 collagen levels induced by MTX was observed actual effects (P < 0.05). Similarly, the protective effect of MG against MTX was confirmed by histological examination. In conclusion, MG treatment reduced the negative effects of MTX on bone damage by improving BMD and modulation of RANKL, IL-6, TNF-α, OPG and type1 collagen levels in the rats.