ABSTRACT
Experiments were carried out on rats with lathyrism, which was induced by adding semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a 30% reduction in the body weight and an increase in.organ weight coefficients. Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue degradation, cartilage growth, 46% decrease of the calcium level in the femur. It has been detected essential structural changes in extracellular matrix based on the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme for the collagen development, showed 5-fold decrease in the aorta tissues. The level of formaldehyde, a nonenzymic cross-links developer, has been measured in the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione) administration and then fluorimetric determination of formaldimedone. Under semicarbazide load, the formaldehyde level in the liver tissue was reduced by 47%. Therefore, semicarbazide influences not only the enzymic development of aldehyde groups in collagen, but the level of other aldehydes, which can cause cross-links. This experimental model of lathyrism is appropriate for investigation of the lysyl oxidase inhibitors effect on extracellular matrix.
Subject(s)
Collagen/metabolism , Disease Models, Animal , Lathyrism/metabolism , Protein-Lysine 6-Oxidase/metabolism , Animals , Aorta, Thoracic/enzymology , Aorta, Thoracic/metabolism , Body Weight , Bone and Bones/enzymology , Bone and Bones/metabolism , Formaldehyde/metabolism , Joints/enzymology , Joints/metabolism , Lathyrism/chemically induced , Lathyrism/enzymology , Male , Organ Size , Rats , Rats, Wistar , Semicarbazides/pharmacology , Skin/enzymology , Skin/metabolismABSTRACT
Under intratracheal asbestos fibers installation it has been investigated NO synthesis in the lung and liver tissues of Wistar rats by EPR method. Asbestos A6-45, sifted through the sieve with size 0.1 mm, has been administrated in a dose of 5 mg/kg. To evaluate the NO synthesis EPR and NO-trap methods have been used. The amplitude of EPR signal "trap-NO" in the lung samples was 12, 16 and 14 times greater than in controls on the 3th, 6th and 10th days after asbestos installation and was corresponding to NO rate of about 2 mkmol/(g x h). In the liver samples of asbestos-stimulated animals the NO level contained in the non-heme iron nitrosyl complexes was about 2 mkmol/g. Thus, the asbestos fibers stimulate NO synthesis not only in the lung tissue, but also in other organs. The obtained data shows that under NO hyperproduction certain changes in iron metabolism take place, such as: the decrease of transferrin iron and the accumulation of ferric iron not bound with transferrin. The accumulation of ferric iron not shielded by proteins is one of the oxidative stress triggers.
Subject(s)
Asbestos/toxicity , Iron/metabolism , Liver/drug effects , Lung/drug effects , Nitric Oxide/biosynthesis , Animals , Intubation, Intratracheal , Iron/blood , Liver/metabolism , Liver/pathology , Lung/metabolism , Lung/pathology , Male , Mineral Fibers , Nonheme Iron Proteins/metabolism , Rats , Rats, Wistar , Transferrin/metabolismABSTRACT
A method for endogenous formaldehyde (FA) level evaluation has been worked out. The method involves the administration of dimedone, which forms the stable complex with FA, and the determination of formaldimedone concentration in biological samples by the fluorescence approach. The method was tested on rat's models of FA metabolism modulation. Animals received FA (10 mg/kg); or methylamine - substrate of FA-generating enzyme SSAO, (250 mg/kg); or semicarbazide - SSAO inhibitor, (200 mg/kg). Concentration of FA bound with dimedone in the liver tissue were, correspondingly: 7.5 +/- 1.5 mkg/kg; 5.4 +/- 0.9 mkg/kg; 2.4 +/- 0.7 mkg/kg; control - 4.2 +/- 1.4 mkg/kg. Obtained data indicate, that the elaborated method gives reliable information about FA level.
Subject(s)
Cyclohexanones/chemistry , Formaldehyde/analysis , Liver/chemistry , Animals , Cyclohexanones/metabolism , Formaldehyde/metabolism , Liver/metabolism , Models, Animal , Rats , Spectrometry, FluorescenceABSTRACT
Subchronic administration of semicarbazide in the experiment with the rats was used to reduce the formaldehyde level in the organism in order to reveal the interaction between formaldehyde metabolism and biochemical parameters, which define the oxidant-antioxidant system condition and NO metabolism. It has been found that under semicarbazide impact the generation of free radicals, ROS, nitrite and nitrate were enhanced while aldehydes level was reduced that resulted from not only semicarbazide effect like the aldehydes acceptor, but the formaldehyde synthesis slowdown and acceleration of its transformation into format as well. We suppose that formaldehyde plays certain role in the development of connective tissue pathology.
Subject(s)
Acid-Base Equilibrium/drug effects , Formaldehyde/metabolism , Nitric Oxide/metabolism , Semicarbazides/toxicity , Animals , Connective Tissue Diseases/metabolism , Formates/blood , Formates/urine , Liver/drug effects , Liver/enzymology , Liver/metabolism , Lung/drug effects , Lung/enzymology , Lung/metabolism , Myocardium/enzymology , Myocardium/metabolism , Nitrites/blood , Nitrites/urine , Rats , Rats, WistarABSTRACT
The microsomal fraction of the rabbit skeletal muscles contains structures which absorb Ca2+ and where ATPase-aminohydrolase activities are pronounced. Electrophoresis of this fraction in the saccharose density gradient results in separation of a considerable amount of soluble proteins including creatine kinase, as a high ATPase activity and absorbing Ca2+ to an inconsiderable extent. The activity of creatine kinase in the microsomal fraction of the rabbit and rat skeletal muscles is not so high to provide for ATP regeneration from creatine phosphate in the amount sufficient for any considerable transport of Ca2+. In the microsomal fraction of the myocardium, as distinct from the skeletal muscles creatine kinase is strongly bound with its structural components and is not separated by electrophoresis.
