ABSTRACT
Alzheimer's disease (AD) is the most common proteinopathy, which is accompanied by a steady decrease in the patient's cognitive functions with a simultaneous accumulation of amyloid plaques in brain tissues. Amyloid plaques are extracellular aggregates of amyloid ß (Aß) and are associated with neuroinflammation and neurodegeneration. Unlike humans and all other mammals, rats and mice do not reproduce AD-like pathology because there are three amino acid substitutions in their Aß. Amyloid plaques form in the brains of transgenic mice with overexpression of human Aß, and such mice are therefore possible to use in biomedicine to model the key features of AD. The transgenic mouse line APPswe/PS1dE9 is widely used as an animal model to study the molecular mechanisms of AD. A study was made to characterize the APPswe/PS1dE9/Blg subline, which was obtained by crossing APPswe/PS1dE9 mice on a CH3 genetic background with C57Bl6/Chg mice. No difference in offspring's survival and fertility was observed in the subline compared to wild-type control mice. Histological analysis of the brain in the APPswe/PS1dE9/Blg line confirmed the main neuromorphological features of AD and showed that amyloid plaques progressively increase in number and size during aging. The APPswe/PS1dE9/Blg line was assumed to provide a convenient model for developing therapeutic strategies to slow down AD progression.
Subject(s)
Alzheimer Disease , Cerebral Amyloid Angiopathy , Mice , Humans , Rats , Animals , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Mice, Transgenic , Amyloid beta-Peptides/genetics , Amyloid beta-Peptides/metabolism , Plaque, Amyloid/genetics , Cerebral Amyloid Angiopathy/genetics , Cerebral Amyloid Angiopathy/complications , Cerebral Amyloid Angiopathy/metabolism , Brain/metabolism , Disease Models, Animal , MammalsABSTRACT
The experiment was carried out on 120 female white Wistar rats, to study the endothelio- and osteoprotective action of the combination of rosuvastatin with L-norvaline in the model of experimental osteoporosis. It was found that, after ovariectomy in rats, endothelial dysfunction of the vessels of the microcirculatory bed of bone tissue develops, leading to the appearance of osteoporosis, but the combination of the studied drugs prevents the decrease in the level of microcirculation in the bone tissue, thereby preventing the thinning of bone trabeculae and preventing the occurrence of microfractures in them.
ABSTRACT
We performed correction of endothelial dysfunction with phenol derivatives KUD-259 and KUD-974 containing heteroatomic and heterocyclic structures. Pharmacological activity of KUD-259 and KUD-974 surpassed that of L-norvaline, a non-selective arginase inhibitor.
Subject(s)
Arginase/antagonists & inhibitors , Phenol/chemistry , Thrombin/chemistry , Animals , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/pharmacology , Rats , Rats, Wistar , Signal Transduction/drug effects , Valine/analogs & derivatives , Valine/pharmacologyABSTRACT
In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing.
ABSTRACT
The osteoprotective effect of resveratrol and a combination of resveratrol with enalapril has been investigated in white Wistar female rats with experimental osteoporosis. It is established that, in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of the osteal tissue is developed, resulting in the occurrence of osteoporosis. Resveratrol and the combination of resveratrol with enalapril prevented depression of the microcirculation level in the osteal tissue, thus preventing the thinning of osteal trabecules and preventing their microfractures.
Subject(s)
Enalapril/therapeutic use , Endothelium/physiopathology , Microcirculation/drug effects , Osteoporosis/drug therapy , Stilbenes/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Bone and Bones/blood supply , Bone and Bones/physiopathology , Drug Therapy, Combination , Endothelium/blood supply , Female , Ovariectomy , Rats , Rats, Wistar , Resveratrol , Vasodilator Agents/therapeutic useABSTRACT
The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed.
Subject(s)
Arginine/administration & dosage , Endothelium/drug effects , Hypertension/prevention & control , Placenta/drug effects , Pre-Eclampsia/drug therapy , Albuminuria/prevention & control , Animals , Arginine/therapeutic use , Blood Pressure/drug effects , Endothelium/physiology , Female , Humans , Injections, Intraperitoneal , Microcirculation/drug effects , Microcirculation/physiology , NG-Nitroarginine Methyl Ester/administration & dosage , NG-Nitroarginine Methyl Ester/adverse effects , Nitric Oxide Synthase Type III/metabolism , Placenta/blood supply , Pre-Eclampsia/chemically induced , Pre-Eclampsia/metabolism , Pregnancy , RatsABSTRACT
Intragastric methionine (3 g/kg daily for 7 days) elevates homocysteine concentration and increases the endothelial dysfunction coefficient. This protocol of methionine treatment is an adequate model of hyperhomocysteine-induced endothelial dysfunction and can be used for studies of the endothelio- and cardioprotective effects of drugs.
Subject(s)
Endothelium, Vascular/pathology , Hyperhomocysteinemia/physiopathology , Vascular Diseases/physiopathology , Animals , Endothelium, Vascular/drug effects , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/drug therapy , Methionine/therapeutic use , Rats , Vascular Diseases/drug therapy , Vascular Diseases/etiologyABSTRACT
In tests on a group of 250 rats, we studied (i) the level of microcirculation in the muscles of a healthy limb in the norm and (ii) the dynamics of microcirculation for 6 h after treatment with pentoxifylline in a dose of 60 mg/kg dose and L-arginine in a dose of 30 and 200 mg/kg. The chronic ischemia was modeled by excision of basic femoral artery. There was no significant difference in pentoxyfilline-treated animals in comparison to the control. In the group treated with L-arginine in a dose of 30 mg/kg, a significant increase in microcirculation was observed on the 28-th day of experiment. In the group treated with L-arginine in a dose of 200 mg/kg, there was an increase of microcirculation in all terms of the experiment in comparison to the control. The results of laser doppler flow measurements are correlated with the results of morphological investigation.
