Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Methylbenzoxime as a therapeutic agent for glucocorticoid-induced osteoporosis in rats

Mingcong Ding¹, Pandeng Wei², Xuchang Hu¹, Tongqun Yang¹, Mingxuan Yang¹, Qian Zhang¹, Lin Wan¹

¹Department of Orthopaedics, Gansu Provincial Key Laboratory of Bone and Joint Disease; ²Urgent Care Centre, The Second Hospital Affiliated to Lanzhou University, Lanzhou 720030, China.

For correspondence:- Lin Wan Email: VOraleelawon@yahoo.com Tel:+869318942262

Accepted: 24 February 2019 Published: 31 March 2019

Citation: Ding M, Wei P, Hu X, Yang T, Yang M, Zhang Q, et al. Methylbenzoxime as a therapeutic agent for glucocorticoid-induced osteoporosis in rats. Trop J Pharm Res 2019; 18(3):563-570 doi: 10.4314/tjpr.v18i3.17

© 2019 The authors.
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Abstract

Purpose: To investigate the effect of methylbenzoxime on dexamethasone-induced rat model of osteoporosis.

Methods: Osteoporosis rat model was prepared by administration of dexamethasone to rats for sixty days. The rats were then divided into five groups of five animals each: normal control, untreated, and 2, 5 and 10 mg/kg treatment groups. All rats were administered dexamethasone for 60 days. Thereafter, rats in the three treatment groups received daily doses of 2, 5 or 10 mg/kg methylbenzoxime for 15 days, while rats in normal control and untreated groups were given equivalent volumes of normal saline in place of methylbenzoxime. After treatment, the rats were sacrificed, and the femur removed for histological assessment of pathological changes using H&E staining. expressions of Wntn signalling pathway proteins in osteoblasts were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot assays.

Results: Methylbenzoxime inhibited osteoblast proliferation, as revealed from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It increased the expression of osteoprotegerin and downregulated receptor activator for nuclear factor-kappa B ligand. Dexamethasone decreased the expression of Wnt signalling pathway proteins in osteoblasts. However, treatment of the dexamethasone-exposed osteoblasts with methylbenzoxime reversed the inhibition of expressions of Wnt signalling pathway proteins. In vivo studies showed that methylbenzoxime treatment mitigated dexamethasone-induced pathological features in femur. In osteoporotic rats, methylbenzoxime significantly up-regulated the expression of osteocalcin but down-regulated the level of collagen-type I fragments, relative to the untreated group. The effect was significant in the 5 and 10 mg/kg treatment groups, when compared with 2 mg/kg group.

Conclusion: Methylbenzoxime prevents dexamethasone-induced osteoporosis in vitro and in rats. Therefore, it is a potential therapeutic agent for the management of osteoporosis.

Keywords: Glucocorticoids, Osteoporosis, Osteoprotegerin, Osteocalcin, Osteoblasts, Dexamethasone, Methylbenzoxime