Effect Of Somatostatin Analogue Octreotide Research Articles

Anti-inflammatory Effect of Somatostatin Analogue Octreotide on Rheumatoid Arthritis Synoviocytes.

Somatostatin and its analogues are known to have modulatory effects on immune response and their anti-proliferative, anti-angiogenic, and analgesic properties make them attractive candidates for a therapeutic use in immune-mediated diseases, such as rheumatoid arthritis. Here, we demonstrate the ability of the somatostatin analogue octreotide to inhibit interleukin-15 and to increase interleukin-10 production by rheumatoid arthritis fibroblast-like synovial cells maintained in a chronic inflammatory state. We also prove that the inhibitory effect of octreotide on interleukin-15 and tumor necrosis factor-α production depended on the increase in interleukin-10, since neutralizing anti-interleukin-10 antibody was able to partially reverse this inhibition. In addition, our observations suggest an octreotide control on purinergic signaling, with an inhibitory effect on purinergic P2X and P2Y receptors activation. This would have great implications, considering the roles of P2 receptors in the onset of inflammation. Data here reported extend knowledge on the biological action of octreotide and underline its multiple effects on immune response, which could make octreotide an attractive and valid support for the therapy of diseases where several inflammatory mediators are involved, such as rheumatoid arthritis, and in which the simultaneous action on different aspects can be a successful strategy.

Octreotide inhibits proliferation and invasion of MHCC97-H cells in vitro and in vivo

ObjectiveTo figure out the effect of somatostatin analogue Octreotide on proliferation and invasion of human hepatocellular carcinoma cell MHCC97-H and the underlying mechanism in vitro and in vivo. MethodsMHCC97-H cells were treated with Octreotide at the concentration of 0.2 ug/mL in vitro, proliferation related to time was evaluated. After treated with Octreotide at the concentration of 0.2 ug/mL for 48 h, MHCC97-H cells were observed by transmission electron microscope. Cell proliferation was detected by MTT assay after MHCC97-H cells were treated with Octreotide at different concentrations including 0.05, 0.1, 0.2, 0.4, 0.6 and 0.8 ug/mL for 36 h in vitro. 27 nude mice, in which MHCC97-H tumor mass was planted orthotopically, were divided into 3 groups randomly including control group (intraperitoneal injection with equal volume normal saline; n=8), low dose treated group (intraperitoneal injection with Octreotide at 50 ug/kg·d; n=9) and large dose treated group (intraperitoneal injection with Octreotide at 200 ug/kg·d; n=10). All mice were raised for 35 d and sacrificed. The information about survival time, the weight at death point and the pathology change of liver and lung was collected. The expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases-2 (MMP-2) in mouse HCC tissues were detected by immunohistochemistry finally. ResultsMTT assays showed that Octreotide inhibited the proliferation of MHCC97-H cells significantly. Apoptosis cells were found by transmission electron microscope after treatment with Octreotide at 0.2 ug/mL for 48 h in vitro. The proliferation was inhibited significantly by Octreotide in a dose-dependant manner (r=0.86, P<0.01). Compared with control group, the treated group had the heavier weight at death point and lower intrahepatic metastasis ratio (P<0.05), meanwhile, there was not significant difference in treated groups (P>0.05). The positive expression ratios of VEGF and MMP-2 in treated groups were lower than those in control group (P<0.05), while there was no apparent difference in treated groups (P>0.05). ConclusionOctreotide could inhibit the proliferation of MHCC97-H cells in vitro via inducing apoptosis and the inhibitory function acts in a dose-dependant manner. Octreotide could improve survival of mice with MHCC97-H cells and inhibit the metastasis of MHCC97-H cells in vivo. Regulation of VEGF and MMP-2 expression by Octreotide would be involved in its inhibition in vivo.

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

Background Octreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect. Methods Forty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 μg kg −1 h −1 intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mg kg −1 dose. Results Two-way ANOVA revealed significantly fewer ( P = 0.0003) mean ± SD weighted piritramide dose requirements in the octreotide group (19.5 ± 6.3 μg kg −1 h −1) than in the control group (35.7 ± 8.2 μg kg −1 h −1). Dunnett’s two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure ( P = 0.722), heart rate ( P = 0.579) and respiratory rate ( P = 0.823) between the octreotide group (80 ± 10 mm Hg, 74 ± 12, 14 ± 2) and the control group (82 ± 9 mm Hg, 76 ± 11, 15 ± 3), respectively. Conclusion We demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.

Effect of somatostatin analogue octreotide injected into the third cerebral ventricle on pentagastrin-induced gastric acid secretion in rats

To investigate the effect of long-lasting somatostatin analogue octreotide (Oct) injected into the third cerebral ventricle (TCV) on gastric acid secretion in rats. TCVs were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later acute gastric lumen perfusion was carried out and gastric acid was continuously washed with 37 degree Celsius saline by a perfusion pump. Gastric perfusion samples were collected every 10 min and titrated by 0.01 moL/L NaOH to neutral. On the basis of subcutaneous (sc) injection of pentagastrin (G-5, 160 microg/kg), Oct (0.025 microg, 0.05 microg, 0.1 microg, n=12 in each group) or vehicle (pyrogen-free physiological saline, n=10) was injected into the TCV. Before and after the TCV injection, 1 h total acid output (TAO) was determined and experimental data were expressed in change rate (%) of TAO. Oct (0.025, 0.05 and 0.1 microg) injected into the TCV resulted in change rate of 1.56% (P>0.05), 20.21% (P<0.01) and 37.82% of TAO (P<0.001), respectively. Moreover, comparison in change rate of TAO among these 3 doses showed P<0.05 between 0.025 microg and 0.05 microg, P<0.01 between 0.025 microg and 0.1 microg, and P<0.05 between 0.05 microg and 0.1 microg. However, sc injection of 0.05 microg Oct had no effect on G-5 stimulated gastric acid secretion. Octreotide injected into the third cerebral ventricle inhibits gastrin-induced gastric acid secretion in a dose-dependent manner.

The effect of somatostatin analogue on expression of connective tissue growth factor gene of rat hepatic stellate cells

To investigate the effect of somatostatin analogue-octreotide (OCT) on expression of connective tissue growth factor (CTGF) gene of murine hepatic stellate cells (HSCs) in vitro. HSCs separated from Sprague Dawley rats by in situ perfusion and Nycodenz gradient were divided into 5 groups. HSCs in 4 out of 5 groups were co-cultured with octreotide at different dosages, and the remaining group served as control. The expression of CTGF and TGF-beta mRNA were assessed by reverse transcription-polymerase chain reaction (RT-PCR). OCT down-regulates the expression of CTGF and TGF-beta mRNA in HSCs. The effect is increased with a dose dependent manner. OCT could exert the inhibitory effect on HSCs by down-regulating the expression of CTGF and TGF-beta. This provides a potential for the prevention and management of hepatic fibrosis.

Dual effects of somatostatin analog octreotide on gastric emptying during and after intragastric fill.

The effect of the somatostatin analog agonist octreotide (Oct) on gastric emptying of 12.5% glucose during and after intragastric fill was examined in nondeprived rats equipped with stainless steel gastric fistulas. The rate of intragastric infusion (1.0 ml/min) and the volumes delivered (6 or 12 ml) were within the ranges typically observed in rats normally ingesting the same stimulus. In experiment 1, a dose-related suppression of glucose emptying during 12-min infusions was obtained in response to Oct (0, 0.0014, 0.014, 0.14, and 1.4 nmol/kg sc) injected 60 min before the test. The highest dose tested yielded a 37% suppression of glucose solute emptying during fill. In experiment 2, the suppression of emptying during fill induced by Oct (1.4 nmol/kg) was reversed by 10 or 40 microgram/kg of the somatostatin antagonist cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl]). The antagonist did not by itself affect emptying. Experiment 3 showed that the suppression of emptying obtained with 0.14 and 1.4 nmol/kg Oct had disappeared when the gastric sample was withdrawn 36 min after the termination of 12-min glucose infusions. Experiment 4 showed that the Oct-induced reductions in emptying during 6- and 12-min infusions, in fact, were reversed within 6 min after infusion offset. The point of transition between suppressed and increased emptying did not depend on time from injection or from infusion onset but was linked to the offset of the intragastric infusion regardless of its duration. The present findings support the notion that separable mechanisms govern gastric emptying during vs. after gastric fill.

Effect of somatostatin analog octreotide on sphincter of oddi motility in humans

Effect of somatostatin analog octreotide on sphincter of oddi motility in humans

Protective effect of the somatostatin analogue octreotide in ischemia/reperfusion-induced acute pancreatitis in rats.

Somatostatin and its stable analogue octreotide are proposed to ameliorate the outcome from acute pancreatitis by inhibiting pancreatic secretion and preventing cell injury. This study investigated the effect of somatostatin analogue octreotide on pancreatic microcirculatory injury (by means of intravital fluorescence microscopy) and enzyme release after ischemia/reperfusion of the pancreas in rats. Octreotide, injected 15 min before the end of 2 h of ischemia as a bolus injection (50 micrograms kg-1 i.v.) or as a continuous infusion (50 micrograms kg-1 h-1 i.v.), attenuated postischemic reperfusion injury of the pancreas as evidenced by a significant (p < 0.05) improvement in capillary perfusion and decrease in leukocyteendothelium interaction in postcapillary venules compared to ischemia without treatment. Pancreas amylase concentration remained unchanged in the octreotide group but increased significantly (p < 0.05) in the ischemia group. These results indicate a protective effect of octreotide against postischemic reperfusion injury of the pancreas in rats.

Somatostatin analogue octreotide modulates metabolism and effects of 5-fluorouracil and 5-fluorouridine in human colon cancer spheroids

To examine if preferential retention of somatostatin analogues observed in some tumors might be used for modulation of effects of cancer drugs by co-treatment with long acting somatostatin analogues, the effects of somatostatin analogue octreotide on the kinetics of 5-fluorouracil (FUra) and 5-fluorouridine (FUrd) metabolism were studied by 19F NMR spectroscopy in multicell tumor spheroids comprised of human colon HT-29 adenocarcinoma cells. Octreotide stimulated the rat of formation of fluorouridinephosphates in FUra-treated cells, but inhibited this rate in FUrd-treated cells. Other elements of fluoropyrimidine metabolism were also altered by co-incubation with octreotide. A flow cytometric analysis indicated that FUra and FUrd arrested cells in the S phase, but co-treatment with octreotide almost eliminated the S-phase cells and induced the appearance of DNA fragments. These observations raise the possibility that somatostatin analogues can be used for specific modulation of fluoropyrimidine effects in tumors bearing somatostatin receptors.

The effect of somatostatin analogue octreotide on amylase secretion from mouse pancreatic acini.

To clarify whether somatostatin has an inhibitory effect on pancreatic acinar cells, we studied the effect of a long-acting analogue of somatostatin, octreotide, on amylase secretion from isolated mouse pancreatic acini. Octreotide (100 nM) had no inhibitory effects on amylase secretion stimulated by secretin or vasoactive intestinal polypeptide (VIP), while reducing the increase of cyclic adenosine 3',5'-monophosphate (cAMP). On the other hand, octreotide inhibited synergistic amylase secretion induced by secretin or VIP in combination with cholecystokinin (CCK). Octreotide also reduced synergistic amylase secretion by secretin or VIP in combination with calcium ionophore A23187. CCK and A23187 did not alter the increase of cAMP induced by secretin and the inhibitory effect of octreotide on cAMP production. Octreotide did not significantly inhibit amylase secretion stimulated by dibutyryl cAMP (dbcAMP) alone, but reduced synergistic amylase secretion by dbcAMP+A23187. Results obtained above reveal that octreotide has a direct inhibitory effect on amylase secretion from mouse pancreatic acini and probably affects stimulus secretion coupling at a point distal to the production of cAMP, besides inhibiting adenylate cyclase.

The effect of somatostatin analog octreotide (Sandostatin) on luteinizing hormone and ovarian steroids in insulin-dependent diabetic women without residual insulin secretion.

In order to determine whether the inhibitory effect of octreotide on luteinizing hormone (LH) secretion and ovarian steroids observed in women with polycystic ovaries (PCO) is a direct or indirect action of the analog, we have investigated the effect of 7 days of octreotide on LH, follicle stimulating hormone (FSH) and ovarian steroids in nine insulin-dependent diabetic women without residual insulin secreting, as in these patients a possibly confusing inhibitory effect of octreotide on endogenous insulin production is excluded. LH and FSH pulsatility over 4 h and hormonal responses (LH, FSH, estradiol, testosterone and androstenedione) to a single subcutaneous injection of buserelin were measured before and after 7 days' treatment with octreotide 100 micrograms subcutaneously twice a day. Octreotide failed to induce a significant reduction in either serum gonadotropin or ovarian steroid levels, although there was a general tendency of hormonal responses to buserelin to be lower with the analog. The effect of octreotide on LH secretion seems to be in correlation with the pretreatment levels which are, in turn, at least determined partly by endogenous insulin secretion. Thus, the results of the present study support the view that insulin has an important influence on LH secretion.