Effect of 5-HT(2) receptor blockade on cadmium-induced acute toxicity.
The protective effect of 5-HT(2) receptor blockade with ketanserin or ritanserin against cadmium liver injury was investigated. Male Wistar rats were injected intraperitoneally with a sublethal dose of cadmium (3.5 mg/kg body weight). Rats were treated with normal saline (group I), ketanserin (3 mg/kg body weight; group II), or ritanserin (3 mg/kg body weight; group III) 2 hr prior and 4 hr after cadmium administration and killed at different time points. Hematoxylin/eosin-stained liver sections were assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Apoptosis was also quantified by the TUNEL assay. Nonparenchymal liver cells and activated Kupffer cells were identified histochemically. Necrosis, hepatocyte apoptosis, nonparenchymal cell apoptosis, and macroscopic and microscopic peliosis were markedly reduced or minimized in ketanserin- or ritanserin-treated rats. The observed protective effect was almost identical for both ketanserin and ritanserin administration. 5-HT(2) receptor blockade exerts a protective effect against acute cadmium-induced hepatotoxicity.
Tzirogiannis
Konstantinos N
KN
Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias Street, Athens 11527, Greece.
Demonakou
Maria D
MD
Papadimas
George K
GK
Skaltsas
Spyridon D
SD
Manta
Georgia A
GA
Kourentzi
Kalliopi T
KT
Alexandropoulou
Katerina N
KN
Hereti
Rosa I
RI
Mykoniatis
Michael G
MG
Panoutsopoulos
Georgios I
GI
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D007650:Ketanserin / Q000627:therapeutic use*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D016713:Ritanserin / Q000627:therapeutic use*; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome
D044348:Receptors, Serotonin, 5-HT2; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D002104:Cadmium; D016713:Ritanserin; D007650:Ketanserin