Pathophysiological effects of psychoemotional stress and cyclophosphamide

Abstract

Effects arising in mice acutely or chronically exposed to cyclophosphamide, psychoemotional stress, or both are described. These factors produce similar physiological effects which become synergistic when they act jointly. Key Words: psyehoemotional stress; cyclophosphamide; combined effectsAll living organisms on the Earth are constantly exposed to physical, chemical, and biological factors or agents whose effects are often impossible to differentiate. Hence, models for the investigation of the effects of individual agents and two or more factors acting jointly are necessary.Stress manifests itself as a general (nonspecific) response of the body to various environmental stimuli [4]. For mammals, including man, the most common is psychoemotional stress (PES). While pathophysiological consequences of acute and chronic PES have been investigated in detail, little is known about the dynamics of changes occurring in the body during chronic stress, particularly when PES is combined with chemical mutagens.Our objective was to evaluate temporal variations of the combined effects of PES and the standard chemical mutagen cyclophosphamide ( MATERIALS AND METHODSFour groups of male (CBAxC57B1/6) Fj mice were used. Mice of the first group were exposed to PES Institute of Preventive Toxicology and Disinfection, Ministry of Health of the Russian Federation, Moscow by being immobilized for 4 h daily over a period of 20 days [3] and sacrificed on days 1, 5, 10, 15, 20, and 25 after the start of the experiment (i.e., after the first immobilization session). Mice of the second group were immobilized and given an intramuscular injection of CP (10 mg/kg) 24 h before sacrifice on the indicated days. Group 3 mice were treated with CP but were not exposed to PES. The fourth group consisted of intact mice and served as the control.The severity of PES was evaluated by changes in the morphology of the gastrointestinal tract and adrenals, in the weight of thymus and adrenals, and in the differential white blood cell count. Two replicate experiments were carried out. The data for the test groups were compared with the respective data for the control group. The results were statistically analyzed by Student's t test. Figure 1 shows temporal variations in the weigh of thymus and adrenals. The weight of these organs varied more or less concurrently in each group, and its deviation from the control was the highest on days 10 and 15. Histological studies revealed cicatrizing ulcers in stressed and CP-treated mice on day 10 and secondary ulcers on day 15; the main histological findings on days 20 and 25 were atrophic changes in RESULTS