ABSTRACT
Ultrastructural changes in rat cardiomyocytes were studied after single administration of cyclophosphamide in the therapeutic dose. The major signs of cyclophosphamide-induced damage to cardiomyocytes included moderate lysis of myofibrils, dilation of vesicles in the granular and agranular sarcoplasmic reticulum, and destruction of mitochondria with the formation of myelin-like residual bodies. Ultrastructural changes in cardiomyocyte nuclei primarily manifested in variations of the shape, deep invaginations of the nuclear membrane, and translocation into the subsarcolemmal region.
Subject(s)
Cyclophosphamide/toxicity , Myocytes, Cardiac/drug effects , Animals , Male , Myocytes, Cardiac/ultrastructure , Myofibrils/drug effects , Myofibrils/ultrastructure , Rats , Rats, WistarABSTRACT
Structural reorganization of the myocardium in response to antitumor agents (cyclophosphamide, betulonic acid and its amide) was studied. Cardiotoxic effects of these chemicals manifested in cardiomyocyte contracture and lytic injuries and by significant hemodynamic disorders. The most pronounced lytic and necrobiotic changes in cardiomyocytes were detected after injection of cyclophosphamide followed by betulonic amide; this led to a more pronounced decrease in heart weight as a result of a decrease in total cardiomyocyte count. Antitumor drugs differently changed the ratio of mono- to binuclear cardiomyocytes, which differ by their regeneratory and compensatory adaptive potential.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Cyclophosphamide/pharmacology , Myocardium/metabolism , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Oleanolic Acid/analogs & derivatives , Triterpenes/pharmacology , Animals , Male , Myocytes, Cardiac/metabolism , Oleanolic Acid/pharmacology , Rats , Rats, WistarABSTRACT
Aeration of aqueous solutions of 5,10-methenyltetrahydrofolic acid (MTHF) during exposure to ultraviolet irradiation (lambda 300-390 nm, 240 W/m2, 30 min) slowed down photolysis in comparison with deaerated solutions. The rate of photolysis in the presence of oxygen depended on buffer composition. It did not exceed 6% of the starting amount of MTHF. Photolysis of MTHF included opening of the imidazoline ring, dehydrogenation of the tetrahydropterin portion, and elimination of the p-aminobenzoylglutamate moiety. 6,7-Dimethyltetrahydropterin was used as a model compound to show that protonation of the reduced pterin heterocycle increased its tolerance to oxidation, and UV irradiation did not accelerate this process. The stabilizing effect of protonation of the pterin portion and the presence of the positively charged imidazoline moiety are assumed to hamper MTHF oxidation and photolysis. It is assumed that these factors favored the choice of MTHF molecules as photosensors in light-sensitive proteins in the course of evolution.
