Metformin plus naringin reverses bone alterations in experimental metabolic syndrome

Abstract

There is clinical evidence reporting skeletal abnormalities in metabolic syndrome (MS) but the mechanisms underlying these alterations are still unclear. Objective: to evaluate if the combined treatment of metformin (Met) + naringin (NAR, natural antioxidant) reverses bone alterations in animals with experimental MS.

Adult male Wistar rats were used (5 groups-n=6/group): 1) C: controls; 2) SM: 10% fructose (W/V), drinking water; 3) SM+Met: 100 mg/kg b.w. Met, oral; 4) SM+NAR: 40 mg/kg b.w. NAR, subcutaneous; 5) SM+Met+NAR. Treatments started from day 21 of fructose administration and were completed in 60 days. Systemic biochemical parameters were measured. Bone analysis in tibiae: bone mineral density (BMD), histomorphometry and number of adipocytes, osteocytes and osteoclasts. Statistics: ANOVA/Bonferroni (p<0.05).

SM animals presented higher triglyceride and lower HDL-cholesterol levels than controls. Met+NAR and NAR normalized these values. BMD of SM rats was lower than in the other groups and all treatments reversed this decrease. The proximal tibia's bone volume and trabecular thickness were lower in SM rats than in the other groups. All treatments reversed these parameters. The treatments reversed the increase in trabecular separation in SM rats. Histological analysis of tibia revealed an increase in the n° of adipocytes/mm2 in SM rats that reverted to control values with NAR and Met+NAR (C: 50.21±4.33; MS: 132.63±8.78*; MS+Met: 131.02±19.26*; MS+NAR: 54.21±5.54+; MS+Met+NAR: 49.21±1.92+; *p<0.05 vs C; +p<0.05 vs MS). The number of osteocytes/mm2 was lower (22%) in MS rats and in those treated with Met. NAR and Met+NAR reversed it. The n° osteoclasts/mm2 was higher in MS compared to all groups and Met+NAR reversed it (C: 13.33±1.53; MS: 49.82±3.90*; MS+Met: 24.56±0.35*#; MS+NAR: 20.93±1.41*+#; MS+Met+NAR: 11.40±0.50+; *p<0.05 vs C; +p<0.05 vs MS; #p<0.05 vs MS+Met+NAR).

Although individual NAR treatment shows more promising effects than Met, the combination reverses all changes induced by experimental MS. Met+NAR could result in a new therapeutic alternative for the bone alterations caused by this pathology.