Review of harmful gastrointestinal effects of carrageenan in animal experiments - Research Review

Environmental Health Perspectives, Oct, 2001 by Joanne K. Tobacman

In association with carrageenan-induced intestinal ulcerations, Delahunty et al. (56) observed an increased permeability to large molecules, such as [[sup.3]H]PEG (polyethylene glycol)-900. This finding suggested that the intestinal changes induced by carrageenan may be a factor in subsequent absorption of carrageenan or other large molecules.

Other experimental data. Because it can induce acute inflammation, carrageenan has been widely used in experimental models of inflammation, to assess activity of anti-inflammatory drugs and to study mediators of inflammation (4,61,106,119,120). Injected into an experimental site, such as the plantar surface of a rat's paw, pleural cavity, or subcutaneous air bleb, carrageenan induces an inflammatory response, with edema, migration of inflammatory cells, predominantly polymorphonuclear leukocytes, and possibly granuloma formation (61,120). Undegraded carrageenans in vitro can inhibit binding of basic fibroblast growth factor (bFGF), transforming growth factor [beta]-1, and platelet-derived growth factor but not insulin-like growth factor-1 or transforming growth factor-[alpha] (121).

Macrophage injury and destruction caused by carrageenan may be a factor in the reduced cytotoxic lymphocytic response associated with carrageenan exposure in vivo (122). In addition to depression of cell-mediated immunity, impairment of complement activity and of humoral responses have been reported. Prolongation of graft survival and potentiation of tumor growth have been attributed to the cytopathic effect on macrophages (96,123). Because of its effect on T-cells, carrageenan has been studied for its impact on viral infections with herpes simplex virus types 1 and 2 (124) and HIV-1 (125,126), as well as infections with Chlamydia trachomatis (127).

In experimental systems, undegraded carrageenan has produced destruction of several different cell types in addition to macrophages, including small intestine epithelial cell monolayers (54), androgen-dependent malignant prostatic cells (128), bFGF-dependent endothelial cell line (128), rat mammary adenocarcinoma 13762 MAT cells (129), and human mammary myoepithelial cells (130). Lysosomal inclusions and vacuolation have been observed in macrophages, intestinal epithelial cells, and myoepithelial cells exposed to carrageenan (79,85,131).

Injections of carrageenan were noted to induce sarcomas, as well as mammary tumors in animal models, in an early study (132). In other experiments, mammary and testicular tumors have been observed (69,133). Carrageenan has also been noted to have anticoagulant activity, and large systemic doses have been fatal through nephrotoxicity (4).

Mechanisms for Production of Degraded Carrageenan from Undegraded Carrageenan

Gastrointestinal metabolism of carrageenan to form smaller molecular weight components has been observed by several investigators, who reported that carrageenan of high molecular weight changed during intestinal passage, compatible with hydrolysis yielding lower molecular weight components (9,10,74,75).