Monensin induces apoptosis in the liver tissue and primary hepatocytes of chicks

In this study, monensin (MON) was investigated for its apoptotic and genotoxic effects on chick liver tissue and cytotoxic and apoptotic effects on chick primary hepatocytes isolated from perfused liver tissue. Western blotting and real-time PCR (qPCR) were used to determine the apoptotic effect on primary hepatocytes and liver tissue, and the comet assay was used to determine the genotoxic effect on liver tissue. MON decreased cell viability in primary hepatocytes with increasing concentrations. When administered at concentrations of 1 and 10 ??M, MON increased the levels of apoptotic p53, caspase-3, and caspase-9, and downregulated the expression of the antiapoptotic survivin, Bcl-xl, and Bcl-2 genes (p < 0.05). Furthermore, 100 and 125 ppm of MON increased caspase-3, caspase-9, and p53 protein levels, and downregulated Bcl-2 expression (p < 0.05). Bcl-xl gene expression was downregulated only in the group that received 125 ppm of MON (p 0.05). Changes observed in the expression of the survivin gene were insignificant in both groups (p 0.05). Moreover, 100 and 125 ppm of MON caused comet formation, which is a marker of genotoxicity, in the liver (p < 0.05). Our results indicate that MON induced apoptosis in both primary hepatocytes and liver tissue, and also caused genotoxicity in the liver tissue

Evaluation of the hypoglycemic effect of exendin-4's new oral self-nanoemulsifying system in rats

The objective of this study is to develop a new self-nanoemulsifying system containing exendin-4 with or without enzyme inhibitor chymostatin and to evaluate the effects of oral administration of exendin-4 and exendin-4/chymostatin loaded self nanoemulsifying system on plasma exendin-4, plasma insulin, blood glucose levels and to compare with the oral and subcutaneous administration of exendin-4 in non-diabetic and streptozotocin-induced type 2 diabetic rats. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying system containing ethyl oleate as the oil phase, Cremophor EL (R)/Labrasol (R) as the surfactants and propylene glycol as the co-solvent were prepared. The mean droplet size, polydispersity index, zeta potential and viscosity of exendin-4 loaded self-nanoemulsifying system were found as 24.28 +/- 0.43 nm, 0.17 +/- 0.01, -1.28 +/- 3.61 mV, 79.60 +/- 3.30 m.Pas, respectively. The mean droplet size, polydispersity index, zeta potential and viscosity of exendin-4/chymostatin loaded self-nanoemulsifying system were found as 20.25 +/- 0.35 nm, 0.11 +/- 0.02, -1.85 +/- 2.49 mV, 100.02 +/- 7.65 m.Pas, respectively according to our previous study. In the present study, we focused on long-term physical stability studies, pharmacokinetic studies and pharmacodynamic studies of prepared self-nanoemulsifying systems. According to the long-term physical stability data, exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems were found stable both at 5 degrees C +/- 3 degrees C and at 25 degrees C +/- 60% RH for 12 months. Exendin-4 and exendin-4/chymostatin loaded self-nanoemulsifying systems increased AUC and C-max values in non-diabetic rats compared to the oral exendin-4 solution. In diabetic rats, exendin-4/chymostatin loaded self nanoemulsifying systems increased C-max values compared to the exendin-4 solution. Exendin-4/chymostatin loaded self-nanoemulsifying system decreased inter-subject variability compared to commercial Byetta (R). At 30th minute after administration of exendin-4 loaded self-nanoemulsifying system, exendin-4/chymostatin loaded self nanoemulsifying system and Byetta (R), blood glucose levels decreased to 23%, 25%, 29%, respectively. It has been shown that pharmacodynamic response is close to Byetta (R) with exendin-4/chymostatin self-nanoemulsifying system oral administration. In conclusion, a self nanoemulsifying system was found to be a suitable carrier system, and the combination with enzyme inhibitor chymostatin is thought to be promising for oral delivery of exendin-4

TOXICOKINETIC OF CYPERMETHRIN IN BROILER CHICKENS

The toxicokinetics of single-dose intravenous and intracrop administration of cypermethrin has been described in broiler chickens. Twenty male broiler chickens were distributed in two groups of ten animals each. The animals in the groups mentioned were given cypermethrin in both routes at a single dose of 7.5 mg/kg b.w. Blood samples were collected by the wing vein of chickens at 0.083, 0.25, 0.50, 0.75, 1, 2, 4, 6, 8, 12, 18, 24 and 36 hours after administration of cypermethrin. Determination of serum cypermethrin levels was performed by the gas chromatography-electron capture detection. When the serum concentration-time graph of cypermethrin was evaluated, it was found that this pesticide showed a more convenient distribution tendency in the two-compartment open model. The values of t(1/2 beta), MRT and AUC(0 ->infinity)were 7.35 +/- 0.91 hours, 8.64 +/- 1.59 hours and 8741.98 +/- 1996.66 ng.h/ml, respectively, after intravenous administration of cypermethrin. On the other hand, C-max, t(max), t(1/2a),t(1/2 beta), MRT and AUC(0 ->infinity) values calculated for intracrop applied cypermethrin were 422.75 +/- 99.59 ng/ml, 0.80 +/- 0.15 hours, 0.24 +/- 0.05 hours, 10.97 +/- 2.11 hours, 15.39 +/- 2.56 hours and 4266.51 +/- 967.65 ng.h/mL, respectively. The systemic bioavailability of cypermethrin administered intracrop was 48.80%. From the results obtained, bioavailability of cypermethrin and the MRT at the same time in the body are moderate. These results were considered to be an important indicator in the evaluation and treatment of cypermethrin poisoning in broiler chickens