title: Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone.
abstract: 1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia.
authors.forename: N S
authors.initials: NS
authors.lastname: Ahmad
authors.forename: B A K
authors.initials: BA
authors.lastname: Khalid
authors.forename: D A
authors.initials: DA
authors.lastname: Luke
authors.forename: S
authors.initials: S
authors.lastname: Ima Nirwana
mesh_terms: D000596:Amino Acids / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds; D005609:Free Radicals; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D024505:Tocopherols; D024508:Tocotrienols / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D005290:Ferric Compounds; D005609:Free Radicals; D007375:Interleukin-1; D015850:Interleukin-6; D024508:Tocotrienols; D015675:Osteocalcin; C036020:deoxypyridinoline; D024502:alpha-Tocopherol; D009571:Nitrilotriacetic Acid; D024505:Tocopherols; C020326:ferric nitrilotriacetate