Rat Liver Injury Induced by Hypoxic Ischemia and Reperfusion: Protective Action by Somatostatins is Independent from Changes in Glucose Metabolism

Abstract

Changes in glucose metabolism mediated by natural somatostatin and two derivatives (octreotide, 008) were studied in hypoxic ischemic cell injury of the isolated perfused rat liver. The tested somatostatin and its analogues were previously shown to exert protective actions in liver damage induced by hypoxic ischemia and reperfusion. In isolated perfused livers of rats starved for 24 hours and unstarved rats flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. Glucose and lactate concentration, as well as LDH and GLDH activity, were determined in the effluent. In starved and unstarved rat livers hypoxic ischemia resulted in a substantial enzyme release. In livers harvested from unstarved rats hepatic glucose release was noticed which ceased towards prolonged low flow ischemia. In livers harvested from starved rats containing low hepatic glycogen concentration only minimal hepatic glucose release was present. In starved and unstarved rats pretreatment with somatostatin, octreotide, and 008 significantly reduced LDH and GLDH release (p < 0.001). In unstarved rats natural somatostatin and octreotide pretreatment resulted in a substantial output of glucose during the hypoxic ischemic perfusion period (p < 0.001), whereas livers with 008 pretreatment did not show any difference in glucose release compared to controls. In livers harvested from starved rats neither somatostatin nor octreotide nor 008 pretreatment led to a difference in glucose output observed in controls. Natural somatostatin and octreotide cause a strong hepatic glucose release even under hypoxic ischemic conditions in rat livers with filled glycogen stores. The protective action of natural somatostatin, octreotide, and 008 is not mediated by changes in glucose metabolism, and is not related to endocrine activity.

Upconversion Nanoprobes for the Ratiometric Luminescent Sensing of Nitric Oxide

“…Next, we used these NO-sensing probes to investigate the anti-HIRI behavior of octreotide (Oct), which is a synthetic somatostatin octapeptide that primarily inhibits the secretion of growth hormone . Recent studies have demonstrated that Oct can reduce HIRI significantly, possibly via elevation of NO concentrations, although a detailed mechanism remains unclear. Hepatic ischemia reperfusion surgery was performed on rat models with/without octreotide (Oct) pretreatment, and NO levels in the serum and liver tissue samples were monitored.…”

Nanoconjugates of Ag/Au/Carbon Nanotube for Alkyne-Meditated Ratiometric SERS Imaging of Hypoxia in Hepatic Ischemia

“…HI is a temporary inflow and/or outflow blockage via vascular clamping to decrease intraoperative blood loss, which can cause apoptosis of liver cells and lead to injury of the liver . Oct is a synthetic somatostatin octapeptide whose primary role is to inhibit the secretion of growth hormone, but has been found to significantly reduce hepatic ischemia-reperfusion injury (HIRI) − through a mechanism that remains unclear. Accordingly, herein, through the measurement of liver hypoxia by using the prepared ratiometric SERS nanosensor, we examine whether hepatic ischemia can generate a hypoxic environment.…”

Peer Review #1 of "Treatment with sodium (S)-2-hydroxyglutarate prevents liver injury in an ischemia-reperfusion model in female Wistar rats (v0.1)"

“…We also observed a decrease in the serum concentrations of glucose in both, the IR and HGIR groups compared to SH. It has been demonstrated that liver ischemia impairs glucose metabolism, affecting the gluconeogenesis pathway and decreasing the serum glucose concentration during the late ischemia and reperfusion (Bailey & Reinke 2000;Bloechle et al 1994). There was no significant increase, but a trend, in the serum activity of ALP and the serum concentration of total bilirubin after the induction of IR injury, indicating that IR injury induction affected to a lesser extent the bile ducts than the liver parenchyma.…”