Effect of escitalopram and carbidopa on bone markers in Wistar rats: a preliminary experimental study.

In view of the opposite effects of gut and brain serotonin in bone, the key role of Wnt ß/catenin pathway in osteoblastic proliferation and the controversial bony effects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the effects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on markers of bone turnover and Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0 mg/kg, p.o.) and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days following which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline phosphatase) bone formation and bone resorption markers (receptor activator of nuclear factor κB ligand, tartrate-resistant acid phosphatase 5b) were determined. Our results indicated that escitalopram adversely affected bone as indicated by reduced bone formation and enhanced bone resorption. Further, the effects of escitalopram on bone formation were possibly mediated through gut serotonin while the mechanisms responsible for effects on resorption seem unrelated to gut serotonin. The promising effects of carbidopa on bone formation, as observed in our study, open up exciting possibilities for this drug requiring further investigations.

Differential effects of serotonin reuptake inhibitors fluoxetine and escitalopram on bone markers and microarchitecture in Wistar rats.

Evidence from several studies indicates that the long-term treatment of selective serotonin reuptake inhibitors (SSRIs) is associated with a decrease in bone mass and increase the risk of fractures. The present work evaluated and compared the effect of treatment with two SSRIs viz. fluoxetine and escitalopram on bone biomarkers (P1NP and ßCTX) in male Wistar rats. In addition, the effect of these drugs on bone microarchitecture of lumbar and tibia bones was carried out. Fluoxetine (8.2 mg/kg) treatment for 40 days significantly reduced (P < 0.01) the levels of the P1NP while escitalopram (2.0 mg/kg) was without such effects. Both drugs were devoid of any effects on bone resorption marker ßCTX. The pCREB levels were reduced by both the antidepressants but the reduction was significantly (P < 0.001) marked in case of fluoxetine. The micro-CT data revealed that fluoxetine, but not escitalopram, treatment resulted in reduced bone volume fraction, trabecular thickness and number while increased trabecular separation, trabecular pattern factor and connectivity density in the proximal tibial metaphysis. No significant changes were, however, discernible in lumbar bones. The study shows that fluoxetine reduces bone formation possibly through reduced pCREB mediated by the action of gut serotonin in osteoblasts and that escitalopram can be a better treatment option as far as adverse effects on bone are concerned.

2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid exhibits antidiabetic potential and raises insulin sensitivity via amelioration of oxidative enzymes and inflammatory cytokines in streptozotocin-induced diabetic rats.

Thiazole derivatives are potential candidates for drug development. They can be efficiently synthesized and are extremely active against several diseases, including diabetes. In our present study, we investigated the anti-diabetic, anti-oxidant and anti-inflammatory properties of 2-[(4-Chlorobenzyl) amino]-4-methyl-1,3-thiazole-5-carboxylic acid (BAC) a new thiazole derivative, in a streptozotocin (STZ) induced neonatal model of non-insulin dependent diabetes mellitus (NIDDM) rats. Diabetes was induced by injecting STZ (100mg/kg) intraperitoneally to two days old pups. BAC administration for 3 weeks significantly decreased blood glucose and raised insulin level and improves insulin sensitivity (KITT) level. Additionally, BAC also suppressed several inflammatory cytokines generation as evidenced by decreased levels of serum tumor necrosis factor-α and interleukin-6. In addition, BAC also protects against hyperlipidemia and liver injury. Furthermore, BAC significantly restored pancreatic lipid peroxidation, catalase, superoxide dismutase, and reduced glutathione content. Histological studies of pancreatic tissues showed normal architecture after BAC administration to diabetic rats. Altogether, our results suggest that BAC successfully reduces the blood glucose level and possesses anti-oxidant as well as anti-inflammatory activity. This leads to decreased histological damage in diabetic pancreatic tissues suggesting the possibility of future diabetes treatments.

Serotonin reuptake inhibitors and bone health: A review of clinical studies and plausible mechanisms.

Selective serotonin reuptake inhibitors (SSRIs) are currently the treatment of choice in depression and constitute major portion of prescription in depressive patients. The role of serotonin receptors in bone is emerging, raising certain questions regarding the effect of blockade of serotonin reuptake in the bone metabolism. Clinical studies have reported an association of SSRI antidepressants which with increase in fracture and decrease in bone mineral density. This review focus on recent evidence that evaluate the association of SSRIs with the risk of fracture and bone mineral density and also the probable mechanisms that might be involved in such effects.