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octreotide induces caspase activation and apoptosis in human hepatoma HepG2 cells

World Journal of Gastroenterology 2011年第3期17卷 313-321页

作者： Nikos J Tsagarakis Ioannis Drygiannakis Antonis G Batistakis George Kolios Elias A Kouroumalis Liver Research Laboratory School of MedicineUniversity of Crete Laboratory of Pharmacology School of MedicineDemocritus University of Thrace Department of Gastroenterology and Hepatology University Hospital of Heraklion

AIM: To investigate the role of octreotide on cellular proliferation and apoptosis of human hepatoma (HepG2) cells. METHODS: We studied cellular proliferation, apoptosis and the possible internal caspase-mediated apoptosis pathway involved, after treatment of HepG2 carcinoma cells with octreotide in comparison with the apoptosis caused by tumor necrosis factor-α (TNF-α). Activities of caspase-3, caspase-9, caspase-8 and caspase-2 were studied, while apoptosis was investigated through detection of DNA fragmentation and through identification of apoptotic cells with the annexin-V/propidium iodide flow cytometric method. RESULTS: After an initial increase in HepG2 cellular proliferation, a significant inhibition was observed with 10-8 mol/L octreotide, while TNF-α dose-dependently decreased proliferation. Early and late apoptosis was significantly increased with both substances. octreotide significantly increased caspase-3, caspase-8 and caspase-2 activity. TNF-α signifi cantly increased only caspase-2. Cellular proliferation was decreased after treatment with octreotide or TNF-α alone but, in contrast to TNF-α, octreotide decreased proliferation only at concentrations of 10-8 mol/L, while lower concentrations increased proliferation. CONCLUSION: Our findings are suggestive of caspasemediated signaling pathways of octreotide antitumor activity in HepG2 cells, and indicate that measurements of serum octreotide levels may be important, at least in clinical trials, to verify optimal therapeutic drug concentrations.

关键词： octreotide Hepatocellular carcinoma Apoptosis Caspases Somatostatin

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octreotide ameliorates gastric lesions in chronically mild stressed rats

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World Journal of Gastroenterology 2011年第9期17卷 1135-1142页

作者： Noha N Nassar Mona F Schaalan Hala F Zaki Dalaal M Abdallah Department of Pharmacology and Toxicology Faculty of PharmacyCairo University Department of Biochemistry Faculty of PharmacyMisr International University

AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for *** was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress ***-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed ***,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,Poctreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose *** beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.

关键词： Gastric ulcer Chronic mild stress octreotide Inflammation Oxidative stress Apoptosis Histopathology

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octreotide in Hennekam syndrome-associated intestinal lymphangiectasia

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World Journal of Gastroenterology 2012年第43期18卷 6333-6337页

作者： Siham Al Sinani Yusria Al Rawahi Hamed Abdoon Child Health Department Sultan Qaboos University HospitalMuscat 123Sultanate of Oman

A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.

关键词： Hennekam syndrome Lymphangiectasia octreotide Protein losing enteropathy

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octreotide reverses shock due to vasoactive intestinal peptide-secreting adrenal pheochromocytoma: A case report and review of literature

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World Journal of Clinical Cases 2018年第14期6卷 862-868页

作者： Xiao Hu Wei Cao Min Zhao Department of Emergency Medicine Shengjing Hospital of China Medical University Department of Pathology Shengjing Hospital of China Medical University

Vasoactive intestinal peptide-producing tumors （VIP-oma） usually originate in the pancreas and are chara-cterized by diarrhea, hypokalemia, and achlorhydria （WDHA syndrome）. In adults, nonpancreatic VIPoma is very rare. Herein, we report an unusual case of VIP-producing pheochromocytoma marked by persistent shock, fushing, and watery diarrhea and high sensitivity to octreotide. A 53-year-old woman was hospitalized for sudden-onset hypertension with convulsions, which then rapidly evolved to persistent shock, fushing, and watery diarrhea. Abdominal computed tomography indicated a left adrenal mass, accompanied by bleeding;and marked elevations of both plasma catecholamine and VIP concentrations were documented via laboratory testing. Surprisingly, all clinical symptoms responded swiftly to octreotide treatment. Once surgically treated, hormonal levels normalized in this patient, and the clinical symptoms dissipated. Postoperative pathological and immunohistopathological studies confrmed a VIP-secreting pheochromocytoma with strong, diffuse positivity for somatostatin receptor type 2. During a 6-mo follow-up period, she seemed in good health andwas symptom-free.

关键词： Pheochromocytoma Vasoactive intestinal peptide octreotide Shock Flushing Diarrhea Case report

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octreotide-induced acute life-threatening gallstones after vicarious contrast medium excretion:A case report

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World Journal of Clinical Cases 2021年第25期9卷 7484-7489页

作者： Zong-Hong Han Zhong-Ming He Wen-Hua Chen Cao-Ye Wang Qi Wang Department of Interventional Radiology The First People’s Hospital of ChangzhouChangzhou 213003Jiangsu ProvinceChina

BACKGROUND octreotide is widely used for the treatment of acromegaly,neuroendocrine tumors,and secretory ***,long-term octreotide treatment can increase the incidence of *** contrast medium excretion(VCME)through the hepatobiliary system is well ***,few studies have reported octreotide-induced acute gallstones following *** SUMMARY A 69-year-old man presented with left lower back pain and hematuria caused by a *** patient had a history of polycystic kidney *** occurred following renal artery embolization for a ruptured polycystic *** 5 d of treatment with octreotide,the patient developed acute gallstones and intrahepatic cholestasis which further induced pancreatitis and *** was discharged after hemodialysis,antibiotics,and supportive *** For patients with a high-risk of VCME,octreotide should be cautiously administered and carefully monitored.

关键词： octreotide Gallstones Contrast medium Case report

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Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis

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World Journal of Gastroenterology 2007年第38期13卷 5079-5089页

作者： Xi-Ping Zhang Hua Tian Yue-Hong Lai Li Chen Ling Zhang Qi-Hui Cheng Wei Yan Yun Li Qing-Yu Li Qing He Fei Wang Department of General Surgery Hangzhou First People's Hospital Hangzhou 310006 Zhejiang Province China Department of General Surgery 2^nd Affiliated Hospital of Zhejiang University School of Medicine Hangzhou 310009 Zhejiang Province China Zhejiang University of Traditional Chinese Medicine Hangzhou 310053 Zhejiang Province China Department of Seven Year's Clinical Medicine Shanxi Medical University Taiyuan 310001 Shanxi Province China Department of Gynecology and Obstetrics Hangzhou First People's Hospital Hangzhou 310006 Zhejiang Province China Manufacturing Laboratory Hangzhou First People's Hospital Hangzhou 310006 Zhejiang Province China

AIM: To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP). METHODS: One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-α, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation. RESULTS: The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P octreotide-treated group than in model group at 3 h and 6 h (P octreotide-treated group than in model group at 6 h and 12 h [P < 0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P < 0.05, 57.50 (22.50) and 52.50 (15.00) μmol/L vs 65.00 (7.50) μmol/L; P < 0.01, 57.50 (27.50) and 45.00 (12.50) μmol/L vs 74.10 (26.15) μmol/L, respectively]. The

关键词： Severe acute pancreatitis Baicalin octreotide Renal injury Rats Tissue microarrays

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Efficacy of the long-acting octreotide formulation in patients with thyroid-stimulating hormone-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure

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Chinese Medical Journal 2012年第15期125卷 2758-2763页

作者： ZHANG Chun-fang LIANG Dan ZHONG Li-yong Department of Endocrinology Beijing Tiantan Hospital CapitalMedical University Beijing 100050 China

Background Little information about the current management of patients with thyroid-stimulating hormone （TSH）-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide was contained in the literature. This study aimed to report the efficacy and safety of the long-acting octreotide formulation in patients with TSH-secreting pituitary adenomas after incomplete surgery and octreotide treatment failure. Methods Fifteen patients with TSH-secreting pituitary adenomas （8 men and 7 women）, who previously underwent incomplete surgical resection and/or adjuvant radiotherapy （n=12） and failure of octreotide treatment （n=15）, followed between 2007 and 2010 in Beijing Tiantan Hospital were included in this study. All patients received 1- to 2-months of the long-acting octreotide formulation treatment after the above combination of treatment. Paired samples t-test was used to analysis the variables. Results After two-month duration of the long-acting octreotide formulation treatment, the mean serum free or unbound thyroxine （FT4）（（16.02±1.72） pmol/L） and free triiodothyronine （FT3）（（2.87±0.43） pmol/L） levels of 15 patients significantly decreased compared with those after octreotide-treatment （FT4, （35.36±7.42） pmol/L, P 〈0.001; FT3, （17.85±7.22） pmol/L, P 〈0.001）. Mean TSH levels stayed in the normal range after the long-acting octreotide formulation treatment （（0.72±0.21） mUlL） and were significantly lower than the pretreatment value （（5.27±1.04） mUlL, P 〈0.001）, post-surgery value （（3.37±0.31） mU/L, P 〈0.001） and post-octreotide-treatment value （（4.52±0.41） mU/L, P 〈0.001）. In these patients with TSH-secreting pituitary adenomas there was no evidence of tachyphylaxis. Conclusion The long-acting octreotide formulation may be a useful and safe therapeutic tool to facilitate the medical treatment of TSH-secreting pituitary adenomas in patients who underwent incomplete surgery or need long-term somatostatin analog therapy.

关键词： pituitary adenomas, thyroid-stimulating hormone, long-acting octreotide formulation octreotide surgery

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octreotide inhibits proliferation and induces apoptosis of hepatocellular carcinoma cells

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Acta Pharmacologica Sinica 2004年第10期 140-146页

作者： Hai-lin LIU, Li HUO, Lei WANGDepartment of Gastroenterology, The Ninth People’s Hospital, Shanghai Second Medical University, Shanghai 200011, China

AIM: To study the effect of octreotide on cell proliferation and apoptosis in different hepatocellular carcinoma (HCC) cells and hepatocytes. METHODS: The proliferation of HCC cells (HepG2, SMMC-7721) and hepatocytes (L-02) was determined by MTT assay. Apoptosis was detected either by fluorescent staining, transmission electron microscopy or flow cytometry. The content of AFP in the supernatant of cultured HCC cells was determined by electrochemiluminescence immunoassay. The expression of SSTR subtypes was identified by RT-PCR. RESULTS: The proliferation of HCC cells and L-02 cells was inhibited significantly by octreotide (0.25, 0.5, 1.0, 2.0 and 4.0 mg/L). However, the apoptosis of HCC cells markedly increased in a concentration-dependent manner. Both the apoptosis index and the percentage of apoptotic cells in L-02 cells were significantly lower than those of HepG2 and SMMC-7721 cells. The content of AFP in the supernatant of cultured HepG2 cells treated with octreotide was also statistically reduced.

关键词： hepatocellular carcinoma octreotide apoptosis somatostatin receptors

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Study on protecting effects of Baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis

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World Journal of Gastroenterology 2008年第42期14卷 6551-6559页

作者： Xi-Ping Zhang Guang-Hua Feng Wei Zhu Yang Cai Qi-Jun Yang Tong-Fa Ju Qi xie Wen-Qin Yuan Jie Zhang Zheng Ren Department of General Surgery Hangzhou First People's Hospital Hangzhou 310006 Zhejiang Province China First College of Clinical Medicine Zhejiang University of Traditional Chinese Medicine Hangzhou 310053 Zhejiang Province China Department of General Surgery Second Affiliated Hospital Medical College Zhejiang University Hangzhou 310003 Zhejiang Province China

AIM: To investigate the protective effects and mechanisms of Baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, Baicalin treated group, and octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and Caspase-3, and changes of apoptotic ***: Rat survival at 12 h, expression levels of Bax, Caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both Baicalin and octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, Caspase-3 protein, and inducing apoptosis.

关键词： Baicalin octreotide Severe acute pancreatitis Hepatic injury Tissue microarray Apoptosis

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Effects of octreotide on acute necrotizing pancreatitis in rabbits

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World Journal of Gastroenterology 2004年第14期10卷 2082-2086页

作者： Lászl6Czakó PéterHegyi TamásTakács CsabaGóg AndrásFarkas YvetteMándy Ilona Sz.Varga LászlóTiszlavicz JánosLonovics First Department of Internal Medicine University of SzegedSzegedHungary Second Department of Internal Medicine and Cardiological Center University of SzegedSzegedHungary Department of Microbiology University of SzegedSzegedHungary Biological Department of Pathology University of SzegedSzegedHungary

AIM:To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis,and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS:Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b.m,of 50 g/L sodium taurocholate (NaTC) in the pancreatic ***- operated animals served as *** i mg/kg·b.m. was administered subcutaneously before the induction of *** was taken from the jugular vein before and at 1,3,6,12 and 24 h after pancreatitis induction. Serum activities of amylase,IL-6 and TNF-α and levels of malonyl dialdehyde (MDA),glutathione (GSH),glutathione peroxidase (GPx),catalase and superoxide dismutase (Mn-, Cu-,and Zn-SOD) in pancreatic tissue were measured. RESULTS:Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis,and then returned to control *** tissue concentration of MDA was significantly elevated at 24 h,while the GSH level and GP-x,catalase,Mn-SOD,Cu-,Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the *** pretreatmnent significantly reversed the changes in cytokines and reactive oxygen *** treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes. CONCLUSION:Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in *** octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites,but does not have any beneficial effects on the development of necrotizing pancreatitis.

关键词： Animals Cytokines inhibitors Male octreotide Pancreas Pancreatitis, Acute Necrotizing control Rabbits Reactive Oxygen Species Research Support, Non-U.S. Gov't Taurocholic Acid

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