The Beneficial Role of Filipendula ulmaria Extract in Prevention of Prodepressant Effect and Cognitive Impairment Induced by Nanoparticles of Calcium Phosphates in Rats

Abstract

Mineral components of dental composites are used in many medical and dental applications, including preventive, restorative, and regenerative dentistry. To evaluate the behavioural alterations induced by nanosized particles of novel dental composites, by means of depressive level and cognitive functions, experimental groups of rats were chronically administered with nanosized hydroxyapatite (HA), tricalcium phosphate (TCP), and amorphous calcium phosphate (ACP) with or without simultaneous application of Filipendula ulmaria L. (FU) methanolic extract. The significant prodepressant action was observed in groups solely treated with HA and ACP. Besides, prolonged treatment with ACP also resulted in a significant decline in cognitive functions estimated in the novel object recognition test. The adverse impact of calcium phosphates on estimated behavioural functions was accompanied by increased oxidative damage and apoptotic markers in the prefrontal cortex, as well as diminished specific neurotrophin (BDNF) and gabaergic expression. The results of our investigation showed that simultaneous antioxidant supplementation with FU extract prevented calcium phosphate-induced behavioural disturbances, as well as prooxidative and apoptotic actions, with the simultaneous restoration of BDNF and GABA-A receptors in the prefrontal cortex. These findings suggest that FU may be useful in the prevention of prodepressant impact and cognitive decline as early as the manifestation of calcium phosphate-induced neurotoxicity.

The Antioxidant Supplementation with Filipendula ulmaria Extract Attenuates the Systemic Adverse Effects of Nanosized Calcium Phosphates in Rats

“…The obvious beneficial role of antioxidant supplementation with FU extract on nano-CaP-induced hepatotoxicity cannot be compared to similar reports. However, although already known for its protective role by means of antioxidant and anti-inflammatory effects [ 24 ], the confirmation of benefits of using FU extract following nano-CaP administration could be found only in certain brain regions [ 11 ].…”

“…The mineral components of dental composites in nanoparticles were purchased from Sigma-Aldrich, Germany: hydroxyapatite nanopowder: <200 nm particle size (BET), ≥97%, and synthetic; tricalcium phosphate hydrate nanopowder: <200 nm particle size (BET); and calcium phosphate: amorphous nanopowder and <150 nm particle size (BET). The doses for nanosized calcium phosphates were determined to meet the following criteria, as previously described by Arsenijevic and coworkers [ 11 ]: to achieve the equimolarity, to level the lowest dose of calcium phosphates (HA) that showed toxic effects according to literature data [ 25 ] for experiments performed in vivo with nanosized particles, and to achieve the doses of calcium phosphates daily released from dental composites in vitro [ 26 ]. The route of administration ( per os ) was chosen to mimic the authentic way of application in humans.…”

“…However, the most frequent application of CaPs usually takes place in various interventions in dentistry, such as numerous endodontic treatments [ 6 ], coating in dental implants [ 7 ], failing subperiosteal metal implants [ 8 ], periodontal defects [ 9 ], and restoration of edentulous atrophic ridges [ 10 ]. From the clinical point of view, numerous investigations have been conducted with different CaP polymers, including hydroxyapatite (HA), monocalcium phosphate, dicalcium phosphate, tricalcium phosphate (TCP), tetracalcium phosphate, and amorphous calcium phosphate (ACP), as bioactive components of composites [ 11 ]. However, recent advances in biomaterials direct clinical indications for CaP application to nanoparticles in order to increase their remineralization potential [ 12 ].…”

“…Moreover, numerous tissues and organs were affected by nano-CaPs. Depending on the investigated organ system, there are confirmations for neurotoxicity [ 11 ], nephrotoxicity [ 16 ], hepatotoxicity [ 17 ], and gonadotoxicity [ 18 ]. Since the common pathophysiological mechanisms of nano-CaP toxicities involve oxidative damage, with consequent apoptotic turnover, it is not surprising that cosupplement application of antioxidants has become a routine procedure in the treatment of nano-CaP-induced toxicities.…”

An Overview of Bone Replacement Materials – Biological Mechanisms and Translational Research

“…A recent study demonstrated that the long term administration of hydroxyapatite or tricalcium phosphate nano particles had a significant prodepressant effect in rodents. Also, a prolonged treatment with amorphous calcium phosphate also resulted in a significant decline in cognitive functions, and these adverse effects were accompanied by the increased oxidative damage and apoptosis in the prefrontal cortex (52).…”