Co-administration of omega-3 fatty acids and metformin showed more desirable effects than the single therapy on indices of bone mineralisation but not gluco-regulatory and antioxidant markers in diabetic rats

Biomed Pharmacother. 2020 Jan:121:109631. doi: 10.1016/j.biopha.2019.109631. Epub 2019 Nov 9.

Abstract

Although metformin (Met) is the most recommended anti-diabetogenic drug in type 2 diabetic state, the drug is known to compromise bone integrity. Like metformin, omega-3 fatty acids (ω-3) have gluco-regulatory action; however, it aids bone health. Therefore, the present study investigated the effects of ω-3 and/or metformin in diabetic rats. Fifty rats of ten animals per group were divided into the following: Control; Diabetic untreated; Diabetic + ω-3; Diabetic + metformin (metfm) and Diabetic + ω-3 + metf groups. Diabetes was induced by the administration of streptozotocin (65 mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg b.w., i.p.). Five days afterwards, treatments started and they lasted for 28 days. ω-3 and metformin were administered at 200 and 180 mg/kg b.w., p.o. respectively. The results showed that the induced diabetes was characterised by significant increases in calcium to phosphorus ratio, tartrate resistant acid phosphatase (TRAP), glucose and insulin resistance; but significant decreases in parathyroid hormone(PTH), phosphorus, TAC and hepatic glycogen. Relative to the diabetic control, treatments with ω-3 or metformin caused significant elevations in hepatic glycogen, total alkaline phosphatase (TALP), osteocalcin, PTH, estradiol, and calcium; however, significant decreases in TRAP and glucose. Co-administration of ω-3 and metformin caused more desirable effects on TALP, c-terminal telopeptide of type 1 collagen, estradiol and calcium to phosphorus ratio compared to the single administration. Relative to ω-3, melatonin showed a more favourable effect on calcium to phosphorus ratio; however, the former proved to have more desirable actions on insulin and TAC. Hence, it was concluded that the combined but not the single administration of ω-3 and metformin could be preferably used in the management of bone health in diabetic state.

Keywords: Antioxidant; Bone; Diabetes; Glucose; Metformin; Omega-3 fatty acids.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Biomarkers / metabolism*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Calcification, Physiologic / drug effects*
  • Calcium / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Male
  • Metformin / pharmacology*
  • Rats
  • Rats, Wistar
  • Streptozocin / pharmacology

Substances

  • Antioxidants
  • Biomarkers
  • Fatty Acids, Omega-3
  • Hypoglycemic Agents
  • Insulin
  • Streptozocin
  • Metformin
  • Calcium