Search

Dipeptide carnosine effect on fibroblast proliferation was assessed by changes in intracellular pH (pHi) in human cultivated lung embryonal fibroblasts. pHi was defined by means of fluorescein diacetate (FDA) during 1-7 days of the culture growth. The investigation showed changes in pHi depending on dipeptide concentration and the presence of additives in it. In some cases rat carnosine caused acidification of cells assumed to be a reaction and the presence of additives of metals in the drug. Sometimes an increase in pHi was observed immediately or shortly after acidification of the cells. In this case dipeptide was assumed to have a stimulating influence on fibroblast pHi due to a low concentration of additives in the drug and fast adaptation of cells. Purified carnosine increased pHi immediately after its addition to the incubation medium. The maximum effect was observed after addition of 10 mkg/ml carnosine, delta of pHi was on the average of 0.22. An increase of carnosine concentration to 50-100 micrograms/ml did not lead to increased effect. So, the increase of fibroblast pHi upon introduction of carnosine may be one of the causes of activation of fibroblast proliferation. The pH-metry method may be recommended as an express-test for the evaluation of the degree of a drug purification.

In experiments on 150 guinea pigs, processes of lung wound healing were followed and the more active cellular sources of regeneration were identified. Measurements of cyclic adenosine monophosphate components in the course of lung healing indicated that histologic and electron-microscopic studies would be more informative if done at days 1, 3, 4, 7, and 14 after lung damage. Both cellular and intracellular mechanisms of regeneration were involved in the healing processes. The type II pneumonocyte be designated as a cambial cell of pulmonary parenchyma, for this cell displays the highest proliferative potency and is responsible for the epithelial lining of newly formed alveoli. The formation of these is shown to be assured through functional activity of all cellular alveolar elements (involving intracellular hyperplasia and hypertrophy of ultrastructures and especially dynamic morphological and functional alterations in osmiophilic bodies of type II pneumonocytes) and capillary neoformation.

The influence of carnosine (beta-alanine, alpha-histidine) on the process of lung wound reparation was studied in 90 guinea-pigs. Its efficacy was evaluated microscopically, histologically and by means of electronic microscope. It was established that carnosine, as compared to controls nearly twice accelerates reparative processes in the injured lung by activation of fibroblast proliferation, connective tissue generation and intracellular regeneration. In type II epithelial cells more intensive formation of osmiophilic bodies and lamellar bodies contained in them is observed. The alveolus formation in the wound lips by the 7-8th day after lung injury is going on under the carnosine influence, which is due, probably, to massive excretion of osmiophilic contents from type II epithelial cells and surfactant production. This may be connected with rapid decrease of atelectasis and rapid restoration of lung airness within the wound.