Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide-induced liver injury in rats |
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Authors: | TAMOTSU MATSUHASHI MICHIRO OTAKA MASARU ODASHIMA MARIO JIN KOGA KOMATSU NORIAKI KONISHI ISAO WADA TOSHIHIRO SATO YOUHEI HORIKAWA REINA OHBA JINKO OYAKE NATSUMI HATAKEYAMA SUMIO WATANABE |
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Affiliation: | Department of Gastroenterology, Akita University School of Medicine, Akita City, Akita, Japan |
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Abstract: | Background and Aims: Rolipram is a specific type IV phosphodiesterase inhibitor that suppresses the activity of immune cells and the production of pro-inflammatory cytokines. In this study, we assessed the effect of rolipram on acute liver injury using thioacetamide (TAA)-induced liver injury in rats as a model. Methods: Rats were treated with rolipram (0.5–5 mg/kg, intraperitoneally) or vehicle and injected 30 min later with TAA (100 mg/kg, subcutaneously). Serum transaminase concentrations and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) levels were measured and livers were examined for microscopic changes. Dose-dependent protection against TAA liver injury was based on transaminase levels and inflammatory cytokine production, and was measured 9 h after TAA when the peak release of cytokines occurred. Result: Rolipram suppressed liver injury based on serum aspartate transaminase (AST), alanine transaminase (ALT) and histology and reduced TNF-α, IL-1β and GRO/CINC-1 levels. Rolipram, at doses of 0.5–5 mg/kg, suppressed serum transaminase and TNF-α production in a dose-dependent manner, and these effects were significant at doses of 2.5 and 5 mg/kg. Conclusion: In our rodent model of acute liver injury, rolipram clearly reduced liver damage and inhibited pro-inflammatory cytokine production. These results suggest that specific type IV phosphodiesterase inhibitors, such as rolipram, have potent hepatoprotective effects that are associated with suppressing inflammatory cytokine production. |
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Keywords: | liver phosphodiesterase rolipram thioacetamide tumor necrosis factor-α |
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