Effect of 5-HT2 Receptor Blockade on Cadmium-Induced Acute Toxicity

Abstract

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.

The emerging role of serotonin in liver regeneration

“…In an effort to further understand the effect of serotonergic system activation in the liver we examined the effect of 5-HT2 receptor blockade in cadmium-induced acute hepatotoxicity in rats. The administration of ketanserin or ritanserin (selective 5-HT2 receptor antagonist), prior and after the administration of a sublethal cadmium dose, resulted in a remarkable reduction of inflammatory and apoptotic indices [64]. Based on the above data, the development of serotonin receptor antagonists may be potentially used as therapeutic agents for the treatment of various liver diseases.…”