The role of the cholinergic system in the memory-protecting effects of metformin in a model of scopolamine-induced memory impairment in aged rats.

PURPOSE: As the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions. METHODS: Metformin was administered orally to male Wistar rats (20-22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis. RESULTS: Impaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity. CONCLUSION: Our results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect.

The effect of intravenous lipid emulsion (ILE) on the pharmacokinetic/toxicokinetic dispositions of ivermectin and carprofen in rabbits.

Intravenous lipid emulsion (ILE) has been widely used as an effective antidote in both veterinary and human medicine for the treatment of acute intoxications caused by drugs and pesticides with high lipid solubility. This study was conducted to investigate the effect of ILE co-administration on the kinetic dispositions of ivermectin (IVM) and carprofen (CRP) following intravenous bolus administration at subtoxic doses in rabbits.Twenty-four male New Zealand rabbits weighing 2.78 ± 0.2 kg were used in this study. Rabbits were divided into four groups (Group 1: IVM and Group 2: IVM + ILE or Group 3: CRP and Group 4: CRP + ILE), each group consisting of 6 animals. In the IVM study, Group 1 received IVM (0.6 mg/kg) alone while Group 2 received IVM (0.6 mg/kg) and ILE (2.5 ml/kg). In the CRP study, Group 3 received CRP (12 mg/kg) alone while Group 4 received CRP (12 mg/kg) and ILE (2.5 ml/kg). In both drug groups, ILE was administered 3 times as an i.v. bolus at the 10th min and repeated 4th and 8th h after the drug administration. Blood samples were collected from the auricular vein at various times after drug administration. The drug concentrations in plasma samples were determined by high-pressure liquid chromatography. Kinetic parameters were calculated using a non-compartmental model for both CRP and IVM.The C0 and area under the concentration-time curve from zero up to ∞ (AUC0-∞) values were significantly greater with ILE co-administration (2136 ng/ml and 360.84 ng.d/ml) compared to the IVM alone (1340.63 ng/ml and 206 ng.d/ml), respectively. Moreover, the volume of distribution (Vdss) and clearance (Cl) of IVM were reduced by approximately 42% and 46% with ILE co-administration compared to IVM alone resulting in a reduction of the distribution and slower elimination, respectively. Similar differences in C0, and Vdss values were also observed in CRP with ILE co-administration compared to CRP alone. ILE co-administration changed significantly the kinetic profile of both IVM and CRP in rabbits, supporting the lipid sink theory in which highly lipid-soluble compounds are absorbed into the lipid phase of plasma from peripheral organs such as the heart and brain affected by the acute toxicity of the compounds.

Plasma disposition and faecal excretion of eprinomectin following subcutaneous administration in Saanen and Alpine goats.

Eprinomectin is extensively used in veterinary medicine, particularly in the treatment of internal and external parasites in livestock, including goats. The pharmacokinetic behavior of eprinomectin in plasma and faeces was studied after a single subcutaneous administration in two different goat breeds at a dose of 0.2 mg/kg body weight. The study was conducted on one-year-old female Saanen (n = 8) and Alpine (n = 8) goats in a parallel design. There were no significant differences between Saanen and Alpine goats on the peak plasma concentration (Cmax, 28.59 ± 7.46 ng/mL vs. 37.69 ± 14.89 ng/mL), area under the curve (AUC0-∞, 93.08 ± 11.66 ng.d/mL vs. 116.98 ± 48.36 ng.d/mL), area under the first moment curve (AUMC0-∞, 311.05 ± 67.23 ng.d2/mL vs. 348.25 ± 202.64 ng.d2/mL) and mean residence time (MRT, 3.24 ± 0.77 d vs. 2.74 ± 0.64 d) values. The plasma terminal half-life and the time to reach peak plasma concentration were significantly higher in Saanen goats (T1/2λz, 2.18 ± 0.43 d; Tmax, 1.21 ± 0.25 d) than in Alpine goats (T1/2λz, 1.66 ± 0.41 d; Tmax, 0.79 ± 0.25 d). The results revealed that the plasma concentration of eprinomectin did not differ depending on the breed in Saanen and Alpine goats. However, it was determined that the eprinomectin clearance from the body may vary depending on the breed in goats. The faecal eprinomectin concentration of Saanen and Alpine goats was 90 and 80 times higher than the plasma eprinomectin concentration, respectively. Although high faecal excretion of eprinomectin confers a high efficacy advantage against parasites in the gastrointestinal tract, it may pose an ecotoxicological risk to manure fauna and aquatic organisms with high susceptibility to this compound.