Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone

Clin Exp Pharmacol Physiol. 2005 Sep;32(9):761-70. doi: 10.1111/j.1440-1681.2005.04264.x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / urine
  • Animals
  • Antioxidants / pharmacology*
  • Bone and Bones / anatomy & histology
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Dose-Response Relationship, Drug
  • Ferric Compounds
  • Free Radicals
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Nitrilotriacetic Acid / analogs & derivatives
  • Osteocalcin / blood
  • Rats
  • Rats, Wistar
  • Tocopherols
  • Tocotrienols / pharmacology*
  • alpha-Tocopherol / analogs & derivatives*
  • alpha-Tocopherol / pharmacology

Substances

  • Amino Acids
  • Antioxidants
  • Ferric Compounds
  • Free Radicals
  • Interleukin-1
  • Interleukin-6
  • Tocotrienols
  • Osteocalcin
  • deoxypyridinoline
  • alpha-Tocopherol
  • Nitrilotriacetic Acid
  • Tocopherols
  • ferric nitrilotriacetate