Pharmacokinetics and therapeutic efficacies of fenbendazole in comparison with levamisole in helminth-infected Caspian turtles (Mauremys caspica).

The pharmacokinetics and bioavailability of fenbendazole and levamisole were determined in Caspian turtles after a single intravenous (i.v.) and subcutaneous (s.c.) administration. Thirty turtles diagnosed as naturally infected with Serpinema microcephalus and Falcaustra armenica nematodes received fenbendazole (50 mg/kg) or levamisole (10 mg/kg) by i.v. and s.c. administrations. Blood samples were collected at time 0, 0.125, 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h after drug administration. Plasma drug concentrations were determined by a validated high-performance liquid chromatography method. Data were analyzed by noncompartmental methods. The mean elimination half-life of levamisole was 5.16 h and 12.03 h for i.v. and s.c. routes, respectively, and for fenbendazole, the mean elimination half-life was 25.38 h (i.v.) and 29.77 h (s.c.). The total clearance and volume of distribution at steady-state for levamisole and fenbendazole following i.v. administration were 0.22, 0.44 ml/g/h, and 1.06 and 7.35 ml/g, respectively. For the s.c. route, the peak plasma concentration of levamisole and fenbendazole was 10.53 and 5.24 µg/mL, respectively. The s.c. bioavailability of levamisole and fenbendazole was complete. Considering high anthelmintic efficacy and bioavailability after s.c. administration of levamisole and fenbendazole, and the absence of adverse effects, this route of administration is an easy and efficacious way of treating nematodes in Caspian turtles.

In vitro toxicity of cinnamaldehyde and nanoemulsion of cinnamaldehyde on protoscoleces of hydatid cyst.

Cystic echinococcosis is a major parasitic and zoonotic disease and surgery is the most common treatment of this disease which carries the risk of intraoperative leakage and recurrence. Using scolicidal agent to inactivate cyst contents reduces the risk of recurrence. Considering side effects of available scolicidals and growing interests on natural pharmaceuticals, the present study aimed to evaluate toxicity of cinnamaldehyde (CA), the main component of cinnamon essential oil, and a developed nanoemulsion of cinnamaldehyde (nano-CA) on protoscoleces of hydatid cyst. Nanoemulsion was prepared by the low energy system and characterized by dynamic light scattering to confirm dimensions. For evaluation of scolicidal effects, serial dilutions of CA and nano-CA were mixed with protoscolices suspension and mortality were recorded at 10, 30, and 60 minutes by eosin exclusion test. Albendazole was used as the positive control. The mean diameter of nano-CA was characterized as equal to 88.5 nm, and poly dispersity index was 0.09. After 30 min of treatment, nano-CA, at 50 µg/ml, killed 99.33% of protoscoleces. At the same time point and concentration, CA only caused mortality rate of 26.18%. 30 min-LC50 value of 369.39 µg/ml was obtained for CA, while after 30 min of exposure, nano-CA showed promising rapid activity with LC50 value of 3.22 µg/ml. Nano formulation significantly increased scolicidal activity of CA probably by increasing penetration and tegumental disorganization of protoscoleces. Further in vivo safety studies are needed to introduce nano-CA as a clinically applicable scolicidal agent.

Development and characterization of monoterpene loaded microemulsions as novel scolicidal agents.

Cystic echinococcosis (CE) is one of the most important zoonotic diseases. The primary treatment is surgery and chemical sterilization of the parasitic layers by injection of a scolicidal agent. Available scolicidals possess side effects, and may cause postoperative complications. Several studies reported the scolicidal properties of monoterpene phenols and alcohols such as carvacrol, thymol, and geraniol. The present study aimed to develop, characterize, and assess monoterpene loaded microemulsions as novel green scolicidals products. For this purpose, microemulsions composing 0.37%, 0.75%, and 1.5% of monoterpenoid(s), thymol, carvacrol, and geraniol, alone or in binary or ternary mixtures were formulated. Samples were analyzed by visual inspection, polarizing optical microscope, and dynamic light scattering (DLS). The stability of the samples was evaluated up to a 3-month storage. For the scolicidal bioassay, samples at different concentrations of 200, 100, 50, 25, and 10 µg/ml were added to wells containing 104 viable protoscoleces and mortality rates were recorded at 2, 5, 10, and 20 min after exposure. Results of the present study showed that microemulsions formulated with 0.75% of pure carvacrol or the binary mixture of thymol and carvacrol at 0.375% are promising scolicidal agents.

In vitro and in vivo evaluations of Pelargonium roseum essential oil activity against Trichomonas gallinae.

OBJECTIVE: Pelargonium roseum Willd. (Geraniaceae) is widely grown as an ornamental plant due to its strong pleasant rose-like odor. The present study evaluates the antitrichomonal effect of P. roseum essential oil (EO) against Trichomonas gallinae both in vitro and in vivo and compares it to that of metronidazole (MTZ) as a standard antitrichomonal drug. MATERIALS AND METHODS: In vitro assays were accomplished in multi-well plates containing MTZ and EO at final concentrations of 2.5, 5, 10, 20, 50, and 100 µg/mL. In vivo assay was carried out on 40 experimentally infected pigeons receiving MTZ and EO at doses of 25 and 50 mg/kg. RESULTS: The 24-hr MIC of MTZ was 10 µg/mL, while for EO it was 20 µg/mL. Treatment with MTZ 50 mg/kg after 4 days led to full recovery of infected pigeons however EO 50 mg/kg resulted in the same outcome after 5 days. No mortality or clinical side effects were seen in treated birds. CONCLUSION: The present study introduced P. roseum EO as a potent natural antitrichomonal agent effective against T. gallinae. Bioactive components of P. roseum can be used as potential therapeutic compounds in development of novel antitrichomonal drugs.

Anxiolytic and antidepressant activities of Pelargonium roseum essential oil on Swiss albino mice: Possible involvement of serotonergic transmission.

The anxiolytic and antidepressant activities of the Reunion Geranium (Pelargonium roseum Willd) essential oil (EO) were evaluated in male Swiss albino mice by intraperitoneal administration of 10, 20, and 50 mg/kg bw using elevated plus maze (EPM), open-field test (OFT), and forced swimming test (FST). Moreover, we evaluated whether the 5-HT1A and GABAA -benzodiazepine receptor systems are involved in the anxiolytic effects through the coadministration of WAY-100635 (a selective 5-HT1A receptor antagonist) and flumazenil (an antagonist of benzodiazepine). GC-MS revealed the monoterpene alcohols citronellol (35.9%) and geraniol (18.5%) as the main components of the P. roseum EO. EO was effective in increasing the total number of entries and time spent in the open arms of EPM whereas number of rearing in OFT was significantly decreased in comparison with the control. In the FST, immobility time decreased in EO treated mice. Pretreatment with WAY-100635, but not Flumazenil, was able to reverse the effects of the EO in the EPM and FST, indicating that the EO activity occurs via the serotonergic but not GABAergic transmission. Overall, results of this work showed significant anxiolytic and antidepressant activity of P. roseum EO and confirmed the traditional uses of Pelargonium species as calming agents.