Role of the autonomic nervous system in cyclophosphamide-induced heart mitochondrial dysfunction in rats.
This study was designed to clarify mechanisms responsible for cyclophosphamide-induced cardiotoxicity. Rats were divided into 2 groups: the cyclophosphamide group, which received cyclophosphamide (100 mg/kg) intraperitoneally once a day for 4 consecutive days; and the control group, which remained untreated. In each group, myocardial mitochondrial respiratory function, enzymic activities in the respiratory chain, and ventricular acetylcholine and norepinephrine concentrations were measured. In the cyclophosphamide group, decreases in mitochondrial respiratory function and in enzymic activities in the respiratory chain were observed compared with those of the control group. Administration with cyclophosphamide caused increases in acetylcholine and norepinephrine in the myocardium. As an increase in tissue acetylcholine level is reported to be linked with the genesis of myocardial damage, we conclude that cyclophosphamide-induced cardiotoxicity is closely related to mitochondrial dysfunction and that alterations in the autonomic nervous system might be related to this dysfunction.
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Y
Y
Hanaki
S
S
Sugiyama
N
N
Akiyama
T
T
Ozawa
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D003520:Cyclophosphamide / Q000633:toxicity*; D004579:Electron Transport; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D003520:Cyclophosphamide; D000109:Acetylcholine; D009638:Norepinephrine