Effect of cocaine on cardiac biochemical functions.
The role of cocaine in cardiac ischemia and subsequent reversible and irreversible pathologic changes is well established. Nevertheless, the mechanisms leading to cardiac injury and irreversible cellular changes remain elusive. Reactive oxygen species (ROSs) are the critical mediators of cellular damage during ischemia-reperfusion. To explore the response of cardiac oxidative stress parameters to intravenous (i.v.) And intraperitoneal (i.p.) cocaine exposure, cardiac total glutathione (GSH, GSSG), malonaldialdehyde (MDA), Mn-superoxide dismutase (Mn-SOD), catalase (CAT), GSH-peroxidase (GSH-px), and GSH s-transferase (GST) were measured, along with biochemical and histologic markers indicative of cardiac injury. Repeated i.p. cocaine exposure produced significant impairment in cardiac integrity, demonstrated by increased circulating lactate (2.4-fold; p < 0.0001), creatine kinase (2.2-fold; p < 0.0001), and creatinine levels (1.7-fold; p < 0.0001). Infiltration of neutrophils into myocardial cavities also was evident. These changes paralleled increases in cardiac MDA (25%; p < 0.04), GSSG (55%; p < 0.001), protein carbonyls (23%; p < 0.05), and Mn-SOD (23%; p < 0.05) levels, indicative of oxidative stress, decreases in GSH (35%; p < 0.01), adenosine triphosphate (ATP; 26%; p < 0.04), GSH-px (28%; p < 0.03), CAT (32%; p < 0.01), and GST (50%; p < 0.001) levels. Intravenous cocaine administration also had similar effects on cardiac oxidative stress measures. In conclusion, our data indicate that cocaine administration compromised the heart's antioxidant defense system.
Devi
B G
BG
Research Institute on Addictions, Buffalo, New York 14203, USA.
Chan
A W
AW
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D008054:Lipid Peroxides; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D003042:Cocaine