Differential patterns of cocaine-induced organ toxicity in murine heart versus liver.
To determine cocaine's toxicity in different organs, BALB/c mice were intraperitoneally injected daily for 15 days with either saline or cocaine: 10 mg/kg, 30 mg/kg, or 60 mg/kg. Cardiac function, hepatic pathophysiology, heart and liver apoptosis, and tumor necrosis factor (TNF-alpha) levels were analyzed. After administration of cocaine, cardiac function decreased. Inflammatory cell infiltration and eosinophilic contraction bands were visible in the hearts of mice treated with 60mg/kg cocaine. Moreover, histopathology demonstrated that cocaine caused hepatic necrosis. TdT-mediated dUTP nick end-labeling (TUNEL) staining and DNA ladder analysis indicated that cocaine caused apoptosis in both the heart and liver. Moreover, immunoassay showed that TNF-alpha levels significantly increased in the heart and liver with cocaine administration. However, our RT-PCR study showed that there was no significant difference in either the heart or liver in the levels of mRNA for TNF-alpha between cocaine-treated and saline control mice. The present study demonstrated that cocaine is toxic to multiple organs, and at low dose can induce hepatic damage without gross pathological injury to the heart. The results suggest that the liver is more sensitive than the heart to cocaine toxicity, and induction of apoptosis or TNF-alpha elevation may be a common mechanism responsible for cocaines toxicity.
Wang
J F
JF
The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Ren
X
X
DeAngelis
J
J
Min
J
J
Zhang
Y
Y
Hampton
T G
TG
Amende
I
I
Morgan
J P
JP
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D003042:Cocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D003042:Cocaine