Lymphozytentransformation und Autohämolyse unter Einwirkung höhermolekularer Urinmetabolite als potentielle Urämietoxine

Abstract

Possible toxic effects of lyophilised not dialysable residue from urine of healthy persons obtained by 4 days dialysing against water were investigated. Therefore, the substance dissolved at a concentration of 2.22 mg/ml in Medium TC 199 respectively in physiological saline solution was added with increasing quantities (0.1 to 1.0 ml) to lymphocyte cultures (3 x 10(6) cells in 4 ml medium) and to erythrocytes (3 ml of blood after separation of granulocytes) from healthy persons. Spontaneous 3H-thymidine uptake of the lymphocytes ascertained 5 days after beginning of incubation was markedly depressed with dependence upon the doses up to 30.4% of the control value, whereas only 65.2% was reached after stimulation with 400 mug PHA. In both cases LDH activity in the supernatant culture medium measured as a parameter of cell destruction showed a dose-dependent increase with inverse trend as compared to 3H-thymidine uptake levels. This negative correlation may be due to impaired cell viability as the main cause for depressed lymphocyte transformation. The autohemolysis of the erythrocytes was diminished with dependence upon the doses until to 59.3% of the control value. Therefore, only cytotoxic effects of uremic serum on the lymphocytes may be due to higher molecular urine metabolites retained in uremia whereas increased autohemolysis will be induced by toxins of lower molecular weight.