Autophagy, SMAD-1, and apoptotic pathways are correlated with L-carnitine protective effect against dexamethasone-induced osteoporosis in Wistar rats

Abstract

Osteoporosis (O.P) is a metabolic bone disease characterized by bone mass loss and bone weakness. The cofactor in fatty acid beta-oxidation, L-carnitine (L-C), has been found to regulate osteoblast activity. Therefore, this work aimed to investigate the potential defensive properties of L-C versus dexamethasone (DEXA) induced O.P, as well as the underlying mechanisms. Thirty female Wistar rats were divided randomly into three equal groups (n = 10). The control group: received saline throughout the study; the DEXA-treated group: received DEXA (7 mg/kg/week) I.M. for four successive weeks; the L-C + DEXA treated group: received L-C (100 mg/kg/day, orally) for two weeks followed by L-C+ DEXA for a further four successive weeks simultaneously in the same previous doses and routes. L-C treatment attenuated the decline in femur and body weights, calcium, osteoprotegerin (OPG), and total antioxidant capacity resulting from DEXA administration. In contrast, L-C ameliorated DEXA-induced elevation in alkaline phosphatase and oxidative stress. Furthermore, L-C reduced the expression of an apoptosis-related gene; caspase-3, however, augmented the expression of autophagy-related genes ATG-5 and Smad-1 in rat bone. Histopathological findings further supported the protective effects of LC against DEXA-induced O.P. In conclusion, the current study findings demonstrated the protective effects of L-C on DEXA-induced O.P due to the reduction of oxidative stress, apoptosis, and increasing autophagy and smad-1 protein gene expression. Consequently, L-C can be used as an additive in the treatment of O.P.