Long Chain Omega-3 Polyunsaturated Fatty Acid Supplementation Protects Against Adriamycin and Cyclophosphamide Chemotherapy-Induced Bone Marrow Damage in Female Rats

Int J Mol Sci. 2018 Feb 6;19(2):484. doi: 10.3390/ijms19020484.

Abstract

Although bone marrow and bone toxicities have been reported in breast cancer survivors, preventative strategies are yet to be developed. Clinical studies suggest consumption of long chain omega-3 polyunsaturated fatty acids (LCn3PUFA) can attenuate age-related bone loss, and recent animal studies also revealed benefits of LCn3PUFA in alleviating bone marrow and bone toxicities associated with methotrexate chemotherapy. Using a female rat model for one of the most commonly used anthracycline-containing breast cancer chemotherapy regimens (adriamycin + cyclophosphamide) (AC) chemotherapy, this study investigated potential effects of daily LCn3PUFA consumption in preserving bone marrow and bone microenvironment during chemotherapy. AC treatment for four cycles significantly reduced bone marrow cellularity and increased marrow adipocyte contents. It increased trabecular bone separation but no obvious changes in bone volume or bone cell densities. LCn3PUFA supplementation (375 mg/100 g/day) attenuated AC-induced bone marrow cell depletion and marrow adiposity. It also partially attenuated AC-induced increases in trabecular bone separation and the cell sizes and nuclear numbers of osteoclasts formed ex vivo from bone marrow cells isolated from AC-treated rats. This study suggests that LCn3PUFA supplementation may have beneficial effects in preventing bone marrow damage and partially protecting the bone during AC cancer chemotherapy.

Keywords: anthracycline chemotherapy; bone damage; bone marrow damage; bone marrow toxicity; breast cancer chemotherapy; long chain omega-3 polyunsaturated fatty acids; marrow adiposity; marrow cellularity.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Bone Marrow / drug effects*
  • Bone Marrow / pathology*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cellular Microenvironment / drug effects
  • Cyclophosphamide / adverse effects*
  • Dietary Supplements*
  • Doxorubicin / adverse effects*
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Osteoclasts / metabolism
  • Protective Agents / pharmacology
  • Rats
  • Sex Factors
  • X-Ray Microtomography

Substances

  • Antineoplastic Agents
  • Fatty Acids, Omega-3
  • Protective Agents
  • Doxorubicin
  • Cyclophosphamide