Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

Abstract

BackgroundOsteoporosis is one of the world’s major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare.MethodsWe administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed.ResultsBiomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin, Tartrate-resistant acid phosphatase and Rankl. In femora, baicalein treatments did not alter bone parameters.ConclusionsBaicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed.Electronic supplementary materialThe online version of this article (10.1186/s12986-018-0327-2) contains supplementary material, which is available to authorized users.

Inhibition of Lipoxygenases Showed No Benefit for the Musculoskeletal System in Estrogen Deficient Rats

“…Effects of the LOX inhibitors on body weight, uterus weight or food intake were ruled out since the treatments did not lead to differences in these compared to the OVX group. We did not detect effects of these substances on the whole body composition in our previous studies either (13,16,19). Previously, we detected favorable effects on the capillarization of muscle after subcutaneous injection of Baicalein (15) and oral administration of Zileuton (unpublished data) for up to 4-5 weeks.…”

“…The scan protocol was as follows: 70 kVp, 200 µA, 30 Hz detector frame rate, 360° rotation, 3600 projections, 20x20 mm 2 field of view, 512-pixel matrix and a 40 µm resolution. A phantom block with 5 defined hydroxyapatite elements (0.2, 0.4, 0.6, 0.8 and 1.0 g/cm³) accompanied every scan to convert grey values into bone mineral density (BMD) ( 16 ). 3D OsteoAnalyze software was used to calculate density and volume ( 16 ).…”

“…A phantom block with 5 defined hydroxyapatite elements (0.2, 0.4, 0.6, 0.8 and 1.0 g/cm³) accompanied every scan to convert grey values into bone mineral density (BMD) ( 16 ). 3D OsteoAnalyze software was used to calculate density and volume ( 16 ). Femoral region-of-interest was the head, which was cut in the transition zone from the collum femoris to the trochanter major .…”

“…In addition to that, we demonstrated a beneficial effect of these treatments on the capillarization of the skeletal muscle ( 15 ). The bone healing process was also favorably affected by these LOX inhibitors ( 14 , 16 ). Zileuton therapy improved cortical, callus and total bone volume at the osteotomy site in the tibia in ovariectomized rats ( 14 ), while a Baicalein monotherapy enhanced callus density without improving callus formation rate ( 16 ).…”

Modulation of fracture healing by the transient accumulation of senescent cells

“…Indeed, bone has the exclusive ability to form scar-free tissue de novo, although this process is slower than the typical wound healing process (16). Importantly, manipulation at each stage can change the course of natural fracture healing events, which has been demonstrated by our group previously (17,18). Whether senescent cells appear in the healing skeleton as they do in skin wound healing or how these cells modulate fracture repair is not known.…”