The hepatoprotective effect of putrescine against cadmium-induced acute liver injury.
The hepatoprotective effect of putrescine against cadmium liver injury was investigated. Male Wistar rats were injected with a dose of cadmium (6.5 mg CdCl(2)/kg bodyweight, intraperitoneally). Normal saline (group I) or putrescine (300 micro mol/kg bodyweight; group II) were injected 2, 5 and 8 h later. A number of animals of both groups were killed 0, 12, 16, 24, 48 or 60 h after cadmium intoxication. Liver tissue was histologically assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Apoptosis was also quantified by the TUNEL assay for hepatocytes and nonparenchymal liver cells. The discrimination between hepatic cell subpopulations was achieved histochemically. The mitotic index in hematoxylin-eosin-stained sections and by the immunochemical detection of Ki67 nuclear antigen, (3)H-thymidine incorporation into hepatic DNA, and hepatic thymidine kinase activity were all used as indices of liver regeneration. Both hepatocyte apoptosis and liver necrosis evolved in a biphasic temporal pattern. Nonparenchymal cell apoptosis and peliosis hepatis evolved in a monophasic pattern and were correlated closely. Putrescine administration totally reversed liver necrosis and hepatocyte apoptosis. The time profile of nonparenchymal apoptosis was altered and peliosis hepatis was also totally attenuated. In conclusion, putrescine protected hepatocytes and modulated the mechanism of cadmium-induced acute hepatotoxicity.
Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., 11527 Athens, Greece.
Konstantinos N
KN
Tzirogiannis
Georgios I
GI
Panoutsopoulos
Maria D
MD
Demonakou
George K
GK
Papadimas
Vasiliki G
VG
Kondyli
Kalliopi T
KT
Kourentzi
Rosa I
RI
Hereti
Michael G
MG
Mykoniatis
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002104:Cadmium / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D010382:Peliosis Hepatis / Q000139:chemically induced / Q000473:pathology; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011700:Putrescine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute
D020011:Protective Agents; D002104:Cadmium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011700:Putrescine