The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model.
Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II-VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia. nurulizzah88@gmail.com.
Nurul 'Izzah
N'
Ibrahim
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia. azlina@ppukm.ukm.edu.my.
Norazlina
N
Mohamed
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia. imasoel@ppukm.ukm.edu.my.
Ima Nirwana
IN
Soelaiman
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia. anazrun@yahoo.com.
Ahmad Nazrun
AN
Shuid
D000818:Animals; D001846:Bone Development / Q000235:genetics; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D017102:Fracture Healing / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010024:Osteoporosis / Q000188:drug therapy / Q000235:genetics*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D024508:Tocotrienols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D024508:Tocotrienols; D008148:Lovastatin
fracture healing genes; lovastatin; osteoporotic fracture healing; targeted delivery; tocotrienol