BACKGROUND: Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock and trauma. The use of butyrate, which acts as a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, provides anti-oxidant and anti-apoptotic effects. METHODS: Male Sprague-Dawley (SD) rats model of HI/R were subjected to a partial (70%) hepatic ischemia for 45 minutes (min) after pretreatment with either saline or butyrate, followed reperfusion. 30 rats were randomly allocated to three main experimental groups (n = 10 each): (1) The sham-operated group underwent laparotomy without hepatic ischemia. (2) Butyrate was injected into the tail vein in the butyrate group 30 min before HI/R. (3) The control group underwent the same procedure as the butyrate group but with administration of physiological saline. Rats from each group were randomly euthanized to collect blood and liver samples. RESULTS: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. SD rats that received butyrate displayed reduced HI/R injury compared with controls. Use of butyrate reduced the histologic injury and significantly decreased serum Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. In addition, butyrate decreased myeloperoxidase (MPO) activity and malondialdehyde (MDA) tissue contents. Apoptotic cells in I/R rats were also significantly reduced after butyrate treatment. Furthermore, butyrate also decreased the mean number of apoptotic cells (positively stained for TUNEL) and increased the mean number of proliferating cells (positively stained for Ki-67). The expression levels of TNF-α and IL-6 were attenuated after butyrate treatment. CONCLUSIONS: Our results suggest that butyrate attenuated I/R-induced liver injury through upregulation of intracellular anti-oxidant stress and anti-apoptotic signaling pathways.
BACKGROUND:Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock and trauma. The use of butyrate, which acts as a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, provides anti-oxidant and anti-apoptotic effects. METHODS: Male Sprague-Dawley (SD) rats model of HI/R were subjected to a partial (70%) hepatic ischemia for 45 minutes (min) after pretreatment with either saline or butyrate, followed reperfusion. 30 rats were randomly allocated to three main experimental groups (n = 10 each): (1) The sham-operated group underwent laparotomy without hepatic ischemia. (2) Butyrate was injected into the tail vein in the butyrate group 30 min before HI/R. (3) The control group underwent the same procedure as the butyrate group but with administration of physiological saline. Rats from each group were randomly euthanized to collect blood and liver samples. RESULTS:Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. SD rats that received butyrate displayed reduced HI/R injury compared with controls. Use of butyrate reduced the histologic injury and significantly decreased serum Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. In addition, butyrate decreased myeloperoxidase (MPO) activity and malondialdehyde (MDA) tissue contents. Apoptotic cells in I/R rats were also significantly reduced after butyrate treatment. Furthermore, butyrate also decreased the mean number of apoptotic cells (positively stained for TUNEL) and increased the mean number of proliferating cells (positively stained for Ki-67). The expression levels of TNF-α and IL-6 were attenuated after butyrate treatment. CONCLUSIONS: Our results suggest that butyrate attenuated I/R-induced liver injury through upregulation of intracellular anti-oxidant stress and anti-apoptotic signaling pathways.