Evaluation of resveratrol's protective effect on hydrocortisone-induced growth inhibition in the peripubertal rat epiphyseal plate

Objective

Chronic use of glucocorticoids during childhood can lead to a decrease in hormone release, including ACTH, GH, TSH, and LH, as well as reduced IGF-1 activity. This can result in osteoporotic changes and hinder growth in height. Resveratrol, an antioxidant with phytoestrogen properties, may improve bone health by increasing bone mineral density in postmenopausal women. It has been shown that resveratrol promotes osteoblastic bone formation and reduces osteoclastic resorption. We aimed to investigate the protective effects of resveratrol on the growth inhibition of the epiphyseal plate induced by hydrocortisone in peripubertal Wistar Albino rats.

Methods

Rats were randomized into 6 groups and treated with hydrocortisone (10 mg/kg/day) and resveratrol (10–50–100 mg/kg/day) for 10 days after a standard AP tibia radiograph was taken. Blood and tibia bones were collected and evaluated for bone biomarkers (osteopontin, sclerostin), histopathological measures, and apoptosis markers.

Results

Subcutaneous administration of hydrocortisone for 10 days significantly reduced tibia linear growth, as evaluated by radiography (23.4 % vs. 15.1 %, p<0.001). In the group that received 50 mg/kg/day of resveratrol and 10 mg/kg/day of hydrocortisone together, the tibia growth inhibition disappeared both radiographically and histologically. High-dose resveratrol (100 mg/kg/day) significantly reduced plasma sclerostin (p<0.001) and increased osteopontin blood levels (p<0.05) compared to the control group.

Conclusion

The inhibitory effect of 10 mg/kg/day hydrocortisone on tibia bone was reversed with 50 mg/kg/day oral resveratrol. Resveratrol's phytoestrogen property is thought to accelerate chondrocyte cellular senescence, counteracting hydrocortisone's inhibitory effect on gonadotropin secretion and senescence.