Radioprotection of the Intestinal Mucosa of Rats by Probucol

Abstract

Probucol is a lipid-regulating drug that also has antioxidant properties. This study was designed to test the possibility that probucol could provide radioprotection of the intestine when administered either intralumenally or systemically. Tissue damage was evaluated histologically by quantifying the number of crypts per circumference and the mucosal height. Animals were sacrificed 5 days after 11 Gy of X irradiation. In one series of experiments, a loop of mid small bowel was exteriorized operatively and compartmentalized into segments, each filled with probucol or saline. Intralumenal administration of probucol prior to irradiation led to a significantly greater number of crypts per circumference and mucosal height compared to saline-filled irradiated controls. In another series of experiments, five groups of rats were irradiated: (1) probucol in the small bowel lumen, (2) intravenous probucol, (3) probucol by gavage, (4) probucol added to standard rat chow and (5) saline control. In the rats given probucol intravenously prior to X irradiation, crypt numbers and mucosal height were significantly enhanced. Probucol given by gavage also resulted in protection. Rats fed a diet containing probucol showed no significant protection. Topical administration was more effective than systemic. Probucol protects the intestinal mucosa from acute radiation damage when given topically, intravenously or by gavage, but does not do so when given as a dietary supplement.

Modulation of radiation-induced alteration in the antioxidant status of mice by naringin

“…This may contribute to a rapid scavenging of free radicals. Melatonin, probucol and ascorbic acid have been reported to reduce the concentration of lipid peroxidation and increase the activities of SOD and GPx in rats exposed to total body radiotherapy (Koc et al, 2003;Bonnefont-Rousselot et al, 1999;Bonsack et al, 1999;Jagetia et al, 2003a). Probucol, a lipid soluble antioxidant has been reported to protect against gamma radiation induced oxidative damage in vitro and in vivo (Bonnefont-Rousselot et al, 1999;Bonsack et al, 1999).…”

Models for Evaluating Agents Intended for the Prophylaxis, Mitigation and Treatment of Radiation Injuries Report of an NCI Workshop, December 3–4, 2003

“…Although in most cases the cytokines were given before irradiation, in one study FGF given after irradiation protected oral mucosa of mice (51). Other agents that have been reported to provide protection from GI effects of radiation in animals include amifostine (53)(54)(55)(56), antioxidants (57)(58)(59), elemental diets (60), and MnSOD administered in an HSV viral carrier (61). Inhibitors of TP53 or the absence of TP53 has been shown to protect mice against hematopoietic injury (62) but does not protect the GI system from higher radiation doses (63).…”

Probucol

“…Their ultimate applicability to clinical situations is yet to be determined, but these studies expand the potential of probucol as a general tissue-protecting agent. Probucol appears to protect the gastrointestinal tract from the effects of radiation [18]. Recent studies show the ability of probucol to protect the gastrointestinal tract from the effects of chemical injury.…”

“…Recent studies of a design different than that of the PQRST Trial are beginning to show evidence that probucol does, in fact, inhibit progression of human atherosclerosis [18]. Baldassarre et al [29••] measured carotid artery wall thickness sonographically in three groups of patients with severe hypercholesterolemia.…”