Hyperthermia ameliorates 2,4,6-trinitrobenzene sulphonic acid-induced colitis in rats: the role of heat shock proteins.

Abstract

PURPOSE:

Hyperthermia is known to protect against cellular injury through the expression of heat shock proteins. In this study, the therapeutic effects of hyperthermia on experimental colitis in the rat were evaluated.

MATERIALS AND METHODS:

Male Wistar rats were given a single intracolonic injection of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Hyperthermia was induced in anesthetized rats by placing them in a temperature-controlled water bath. We started the hyperthermic treatment on the day after the enema. The severity of colitis was evaluated pathologically, and the activities of tissue myeloperoxidase were measured 6 days after the induction of colitis. Furthermore, cytokines, and hyperthermia-induced heat shock proteins in colonic mucosa were detected by enzyme-linked immunosorbent assay and Western blotting. We also investigated the effects of geranylgeranylacetone and zinc protoporphyrin IX on the therapeutic effect of hyperthermia.

RESULTS:

Hyperthermia significantly improved the macroscopic scores of colitis. The TNBS-induced increases in the activities of myeloperoxidase in the colonic tissue were blunted significantly in hyperthermia-treated animals. Furthermore, hyperthermia attenuated increases in cytokine-induced neutrophil chemoattractants-1 and tumor necrosis factor-alpha in the colon. Furthermore, hyperthermia induced the production of heat shock proteins in rat colonic mucosa, and the combination of geranylgeranylacetone with hyperthermia further induced the heat shock protein HSP70, which resulted in further improvement of TNBS-induced colitis. On the other hand, the combination of zinc protoporphyrin IX with hyperthermia attenuated the therapeutic effect of hyperthermia.

CONCLUSIONS:

Hyperthermia ameliorates TNBS-induced colitis in rats through the expression of HSP70 and HO-1. It is postulated that hyperthermia may be useful for the treatment of inflammatory bowel diseases.

• Authors: S Kokura, N Yoshida, T Okuda, N Nakabe, N Sakamoto, Y Isozaki, T Hattori, O Handa, T Takagi, Y Naito, T Yoshikawa
• Journal: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group (Int J Hyperthermia) Vol. 23 Issue 1 Pg. 17-28 (Feb 2007) ISSN: 0265-6736 [Print] England
• PMID: 17575720 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Diterpenes
• Enzyme Inhibitors
• Heat-Shock Proteins
• Protoporphyrins
• Tumor Necrosis Factor-alpha
• zinc protoporphyrin
• Trinitrobenzenesulfonic Acid
• Peroxidase
• geranylgeranylacetone

Topics

• Animals
• Anti-Ulcer Agents (metabolism)
• Body Temperature
• Colitis (chemically induced, metabolism, pathology, therapy)
• Colon (cytology, enzymology, metabolism, pathology)
• Diterpenes (metabolism)
• Enzyme Inhibitors (metabolism)
• Fever
• Heat-Shock Proteins (metabolism)
• Male
• Peroxidase (metabolism)
• Protoporphyrins (metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Trinitrobenzenesulfonic Acid (toxicity)
• Tumor Necrosis Factor-alpha (metabolism)