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At least 19 recordsLinked to original sources
PubMed1992

Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma.

BACKGROUND: The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to streptozocin but less frequently causes vomiting. METHODS: In this multicenter trial, we randomly assigned 105 patients with advanced islet-cell carcinoma to receive one of three treatment regimens: streptozocin plus fluorouracil, streptozocin plus doxorubicin, or chlorozotocin alone. The 31 patients in whom the disease did not respond to treatment were crossed over to chlorozotocin alone or to one of the combination regimens. RESULTS: Streptozocin plus doxorubicin was superior to streptozocin plus fluorouracil in terms of the rate of tumor regression, measured objectively (69 percent vs. 45 percent, P = 0.05), and the length of time to tumor progression (median, 20 vs. 6.9 months; P = 0.001). Streptozocin plus doxorubicin also had a significant advantage in terms of survival (median, 2.2 vs. 1.4 years; P = 0.004) that was accentuated when we considered long-term survival (greater than 2 years). Chlorozotocin alone produced a 30 percent regression rate, with the length of time to tumor progression and the survival time equivalent to those observed with streptozocin plus fluorouracil. Crossover therapy after the failure of either chlorozotocin alone or one of the combination regimens produced an overall response rate of only 17 percent, and the responses were transient. Toxic reactions to all regimens included vomiting, which was least severe with chlorozotocin; hematologic depression; and, with long-term therapy, renal insufficiency. CONCLUSIONS: The combination of streptozocin and doxorubicin is superior to the current standard regimen of streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. Chlorozotocin alone is similar in efficacy to streptozocin plus fluorouracil, but it produces fewer gastrointestinal side effects than the regimens containing streptozocin. It therefore merits study as a constituent of combination drug regimens.

Adenoma, Islet Cell↗
PubMed1994

Effect of age and streptozocin concentration on the induction by streptozocin of hyperglycaemia in fasting rats.

The effect of age and streptozocin concentration on the induction by streptozocin of hyperglycaemia in fasting rats is investigated. The data show that there is a dose dependent effect of streptozocin on the hyperglycaemia induced by streptozocin, and 60 mg/kg streptozocin is significantly more effective than 20 or 40 mg/kg streptozocin in inducing hyperglycaemia. Moreover, the hyperglycaemia induced by 60 mg/kg streptozocin is greater in 8 week old rats than in 4 or 6 week old rats, suggesting an influence of age on streptozocin-induced hyperglycaemia.

Aging↗
PubMed1980

Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma.

To evaluate the treatment of advanced islet-cell carcinoma, we randomly assigned 84 patients to streptozocin alone or streptozocin plus fluorouracil. Each regimen was given in five-day courses. The most frequent toxic effects were nausea and vomiting, mild and reversible renal toxicity, and bone-marrow depression with the combination regimen. The combination had advantages over streptozocin alone in overall rate of response (63 vs. 36 per cent) and in rates of complete response (33 vs. 12 per cent). There was no evidence of a preferential response among types of functional tumors. Objective responses were generally of long duration (median, 17 months) and of substantive clinical benefit. Treatment with the combination also yielded a survival advantage over treatment with streptozocin alone (medians, 26 and 16 1/2 months), but this difference is not statistically significant. In spite of gastrointestinal side effects, streptozocin combined with fluorouracil appears to be a valuable treatment for advanced islet-cell carcinoma.

Adenoma, Islet Cell↗
PubMed1996

Reduction by streptozocin of blood glucose utilization during the appearance of the streptozocin induced early hyperglycaemia in fasting rats.

During the fasting state, in which the hepatic glycogen storage is almost depleted, streptozocin administration (60 mg/kg, iv) also induces an early hyperglycaemia. It was found that the blood glucose concentration in the hepatic vein was significantly higher than that in the tail vein before and at 4 hours after the injection of the vehicle without streptozocin. However, the blood glucose concentration in the hepatic vein was insignificantly different from that in the tail vein 4 hours after streptozocin administration. The data are interpreted as showing that streptozocin may reduce blood glucose utilization during the period of early hyperglycaemia induced by streptozocin.

Animals↗
PubMed1994

Hyperlipidemia in streptozocin-diabetic hamsters as a model for human insulin-deficient diabetes: comparison to streptozocin-diabetic rats.

Characteristics of the lipoprotein profile and metabolism of triglyceride-rich lipoproteins in diabetic hamsters were investigated to assess their suitability as a model for human diabetic hyperlipidemia. Diabetes was induced in the hamsters by intraperitoneal injection of streptozocin (30 mg/kg) for 3 days and compared with the results in streptozocin-diabetic rats (50 mg/kg intravenously). Similar degrees of hyperglycemia and hypoinsulinemia were observed 8 to 10 days after the final streptozocin injection in both groups. Fasting plasma lipid concentrations were about 2.5 times greater in hamsters than in rats. Plasma cholesterol was principally associated with high-density lipoprotein (HDL) in both rodents, although the distribution in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was significantly greater in hamsters (44%) than in rats (13%). Diabetes increased the concentrations of triglyceride, cholesterol, and phospholipid 5.6- to 7.8-fold in hamsters, whereas it increased them only 1.3- to 1.6-fold in rats. Diabetic hamsters have a plasma lipoprotein profile similar to that of diabetic man, ie, triglyceride-rich lipoproteins are increased and HDL cholesterol is decreased. The concentration of HDL cholesterol was inversely correlated with the severity of hypertriglyceridemia (r = .76, P < .005). This combination of events does not occur in diabetic rats. Hamsters had a low level of apoprotein B-48-containing triglyceride-rich lipoproteins, although diabetes increased the estimated concentration by fourfold. In rats apoprotein B-48 is the predominant form, but diabetes did not alter the relative proportion of apoprotein B isoforms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Streptozocin-induced diabetes mellitus in the pregnant ewe.

To evaluate the effects of streptozocin on maternal pancreatic beta-cell function, we administered the agent to 14 pregnant ewes at 85 to 90 days' gestation on two occasions, 4 days apart. Intravenous glucose tolerance tests were performed before the initial administration, before the second dose, and 4 weeks after the final dose of streptozocin. There was a significant elevation in maternal fasting blood glucose (82 +/- 8.1 mg/dl before streptozocin and 102.6 +/- 6.8 mg/dl after streptozocin, p less than 0.05). Five late-gestation ewes were used as controls, and a significant elevation in fasting plasma glucose levels was found in the streptozocin-treated animals (71.4 +/- 7.1 mg/dl control vs 102.6 +/- 6.8 mg/dl after streptozocin, p less than 0.05). The glucose tolerance test curves showed a significant elevation 4 weeks after streptozocin compared with before streptozocin (p less than 0.05). The maternal insulin response to streptozocin demonstrated a loss of the second-phase insulin response to the glucose load after one dose of streptozocin and loss of the first phase after two doses. The fetuses of the streptozocin-treated ewes showed a significant elevation in plasma glucose level compared with that of controls (13.3 +/- 0.8 mg/dl, n = 5) vs 42.1 +/- 8.1 mg/dl, n = 10; p less than 0.05, control vs streptozocin, respectively). There was a consistent trend to fetal hyperinsulinemia in the fetuses of the streptozocin-treated ewes, although this did not achieve statistical significance (3.3 +/- 0.8 microIU/ml, n = 5 vs 9.6 +/- 2.5 microIU/ml, n = 10; p = 0.06, control vs streptozocin, respectively). The fetal insulin/glucose ratio was preserved in the streptozocin-treated ewes. Comparison of fetal weights between the control and diabetic ewes showed a significant increase in fetal weight in the fetuses of diabetic ewes (3280 +/- 46 gm in control fetuses vs 3710 +/- 54 gm in diabetic fetuses, p less than 0.05). The alterations in the maternal glucose and insulin response resulting from streptozocin-induced pancreatic beta-cell destruction combined with elevations in fetal glucose, insulin, and weight provides a large animal model suitable for investigation of gestational diabetes in pregnancy.

Animals↗
PubMed1987

Does so-called streptozocin hypertension exist in rats?

Although the existence of so-called streptozocin hypertension seems well established, some reports have indicated that no rise in blood pressure (BP) occurred after streptozocin treatments. To ascertain the streptozocin-induced BP response, normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated with streptozocin, 40 to 45 and 35 mg/kg i.v., respectively, and BP was determined directly and indirectly every week for 3 to 4 weeks. Direct mean BP was determined without anesthesia or restraint through a cannula inserted into the rat's abdominal aorta. Indirect BP was determined at the tail without anesthesia after prewarming the rat in a holder. Compared with control values, indirect BP increased significantly in diabetic WKY 2 weeks after streptozocin treatment. In contrast, direct BP of these rats decreased, compared with control values. Indirect BP of diabetic SHR was as high as that of the controls, whereas direct BP of diabetic SHR decreased significantly 1 week after the treatment and thereafter, compared with control values. These discrepancies between the direct and indirect BP values may be caused by severe emaciation of diabetic rats. Extra pressure in the cuff may be necessary to occlude the bloodstream. These results indicate that under these conditions the value of BP obtained by the direct measurement is more reliable than that by the indirect one; therefore, we concluded that so-called streptozocin hypertension does not exist.

Animals↗
PubMed2002

Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999).

OBJECTIVE: To determine toxic effects of streptozocin given in combination with a diuresis protocol in dogs and establish whether streptozocin is efficacious in treatment of pancreatic islet cell tumors in dogs. DESIGN: Retrospective study. ANIMALS: 17 dogs. PROCEDURE: Medical records were reviewed to obtain information regarding signalment, tumor stage and staging tests performed, number of streptozocin treatments, adverse effects, results of biochemical and hematologic monitoring during streptozocin treatment, tumor dimensions, duration of normoglycemia, and date of death, when applicable. Dogs were compared with a historical control group of 15 dogs treated surgically and medically. RESULTS: 58 treatments were administered to the 17 dogs. Only 1 dog developed azotemia. Serum alanine aminotransferase activity increased in some dogs but decreased when treatment was discontinued. Hematologic toxicoses were rare. Vomiting during administration was uncommon but occasionally severe. Two dogs developed diabetes mellitus after receiving 5 doses. Median duration of normoglycemia for 14 dogs with stage-II or -III insulinoma treated with streptozocin was 163 days (95% confidence interval, 16 to 309 days), which was not significantly different from that for the control dogs (90 days; 95% confidence interval, 0 to 426 days). Two dogs had rapid resolution of paraneoplastic peripheral neuropathy, and 2 others had measurable reductions in tumor size. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that streptozocin can be administered safely to dogs at a dosage of 500 mg/m2, IV, every 3 weeks when combined with a protocol for induction of diuresis and may be efficacious in the treatment of dogs with metastatic pancreatic islet cell tumors.

Animals↗
PubMed1996

Attenuation by nicotinamide of the streptozocin induced early hyperglycaemia in fasting rats.

The effect of nicotinamide on the streptozocin induced early hyperglycaemia in 48-hour fasted rats was investigated. It was shown that 240 or 400 mg/kg nicotinamide significantly attenuated the streptozocin induced early hyperglycaemia. Nicotinamide should be administered no later than 1 hour after the streptozocin administration. Lower level doses of nicotinamide such as 80 mg/kg were unable to attenuate the streptozocin induced early hyperglycaemia. The possibility of nicotinamide offsetting the streptozocin effect was discussed.

Animals↗
PubMed1998

Doxorubicin, streptozocin, and 5-fluorouracil chemotherapy for patients with metastatic islet-cell carcinoma.

Metastatic islet-cell carcinoma is considered to be a slow-growing tumor. Patients are considered for systemic chemotherapy only when they are symptomatic or have impending organ failure, and streptozocin has been the chemotherapeutic agent of choice for the treatment of this disease. Chemotherapy regimens that include streptozocin have shown a higher response rate and a longer duration of response when compared with streptozocin alone. This study evaluates the objective response, response duration, and survival in patients having metastatic islet-cell carcinoma treated with a combination of doxorubicin, streptozocin, and 5-fluorouracil (DSF). Between January 1993 and March 1996, 12 patients were treated with doxorubicin, 40 mg/m2 intravenous bolus on day 1; streptozocin, 400 mg/m2 intravenous bolus on days 1 through 5; and 5-FU, 400 mg/m2 intravenous bolus on days 1 through 5. Courses were repeated every 28 days. Patients were required to have measurable disease, a Zubrod performance status < or = 2, adequate renal and liver function, and a survival expectancy of at least 12 weeks. Six (54.5%) of 11 evaluable patients achieved a partial response (durations in months: 1+, 3.5+, 13+, 17, 22, 26+); one had a minor response, two had stable disease, and two had progressive disease. One patient was lost to follow-up. No complete responses were observed. The median response duration was 15+ months and the median survival 21+ months (range, 3 to 32.5 months). No grade 3 or 4 nonhematologic or hematologic effects were observed. The DSF regimen appears to have significant activity in patients who have metastatic pancreatic islet-cell carcinoma, and patient tolerance of the regimen is excellent, thus warranting further investigation.

Adolescent↗
PubMed1993

Subdiabetogenic streptozocin treatment impairs preimplantation development of mouse embryos.

To estimate the significance of insulin in the regulation of preimplantation embryo growth, female mice received a single subdiabetogenic dose of streptozocin (65 mg/kg intraperitoneally) 8-11 days or 14-17 days before fertilization. Mean glycaemia levels and the number of embryos per mouse did not differ significantly between the streptozocin-treated and control groups. Morphological analysis of preimplantation embryos collected on day 3 of pregnancy revealed significant changes in the distribution pattern of preimplantation embryo stages recovered from streptozocin-treated females. Continuous insulin treatment of streptozocin-treated mice improved the impaired development of preimplantation embryos only in short-lasting experiments. After a long subdiabetic period (14-17 days) the incidence of degenerated embryos was increased in both streptozocin-treated groups. It can be concluded that the subdiabetic state in female mice impairs preimplantation embryo development which could partly be prevented by insulin treatment.

Animals↗
PubMed1997

Light-dependent corneal toxicity in streptozocin-treated rats.

PURPOSE: To find the role of nitric oxide (NO) in streptozocin-induced corneal toxicity in rats. METHODS: Sprague-Dawley rats were injected intraperitoneally with streptozotocin (65 mg/kg). For exposure to light, each rat cage was placed in a box surrounded with aluminum foil and illuminated for 6 hours per day with two 20-W fluorescent lamps at a distance of 50 cm. When not exposed to light, each cage was placed in a dark room. Some animals with and without light exposure also were treated with and without streptozotocin treatment. Control animals did not receive streptozotocin and were housed in a dark room 24 hours a day. Each group contained 15 rats. After 1, 3, 7, and 10 days of light exposure, concentrations of nitrite and nitrate, stable oxidation products of NO, were measured in the aqueous humor. Corneal changes also were examined by electron microscopy after 10 days. To examine specific NO-induced histopathologic changes, several rats were injected subconjunctivally with a balanced saline solution containing the NO-generating agent (S-nitroso-N-acetyl-D,L-penicillamine or (Z)-I-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1, 2-diolate]). RESULTS: Concentrations of nitrite and nitrate were highest in the streptozocin-injected rats irradiated while under the fluorescent lamp. On the 10th day of the streptozotocin injection, the concentrations of nitrite and nitrate in streptozocin-treated rats irradiated while under the fluorescent lamp was almost two-and-a-half times greater than that of nontreated rats reared in the dark (111.37 +/- 7.47 microM, 45.43 +/- 3.91 microM, respectively). Slit-lamp biomicroscopy showed that the corneas swelled gradually and opacified by the third day in the irradiated streptozocin-injected group. The corneas became hazy to the point of indistinguishable detail structures by the 10th day, although those of the other rats were relatively clear at the same time. Histopathologically, ultrastructural changes included the remarkable swelling of intracytoplasmic organelles, including mitochondria, and denaturation of collagen fibril was shown in the streptozocin-injected-irradiated rats by the 10th day. The corneas injected with two NO-generating agents, S-nitroso-N-acetyl-D,L-penicillamine and (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1, 2-diolate, showed similar but more severe changes. CONCLUSIONS: Nitric oxide can cause damage to the mitochondria, the most important energy source of the cell, and induce ultrastructural damage to the corneal endothelium and fibroblast. The authors suggest that NO is associated with the development of corneal cytotoxicity and that NO production and subsequent cytotoxicity can be prevented by blocking to photoactivation.

Animals↗
PubMed1987

Treatment with anti-T-lymphocyte antibodies prevents induction of insulitis in mice given multiple doses of streptozocin.

The importance of T-lymphocytes in the induction of insulitis and hyperglycemia in certain strains of mice treated with multiple subdiabetogenic doses of streptozocin has been a matter of controversy. To understand the role of T-lymphocytes, we treated thymectomized BALB/c ByJ mice with five daily doses of streptozocin (45 mg/kg) and determined the effect of treatment with monoclonal antibodies against T-lymphocyte subsets on the development of diabetes and insulitis. Hyperglycemia (mean glucose of 321 +/- 29 vs. 167 +/- 15 mg/dl in controls) and insulitis were induced in BALB/c ByJ mice given streptozocin. Thy1.2+, L3T4, and Lyt2+ cells were all identified within the islets of diabetic mice. There was a relative paucity of L3T4+ cells and an overabundance of Lyt2+ cells compared with the frequency of these cells found in lymphatic tissues or peripheral blood. Treatment with anti-L3T4 or anti-Lyt2 monoclonal antibodies caused a reduction in splenic T-lymphocyte subsets and attenuated the hyperglycemia to 212 +/- 14 and 197 +/- 16 mg/dl (P less than .001 and .01), respectively, compared with controls and prevented the insulitis induced by streptozocin. Our studies support the hypothesis that an immune response is important to the development of multi-low-dose streptozocin diabetes and indicate that treatment with monoclonal antibodies against the L3T4+ or Lyt2+ T-lymphocyte subsets can attenuate this process.

Animals↗
PubMed1980

Fluorophotometry. III. Streptozocin-treated rats and rats with pancreatectomy.

To determine whether elevated vitreous fluorescence levels are a result of a direct ocular toxic effect of streptozocin or a consequence of the diabetic state, we compared hyperglycemic streptozocin- and insulin-treated or non-insulin-treated rats, hyperglycemia rats with pancreatectomy, and normal rats. Streptozocin, 65 mg/kg, was injected intravenously in one group of hooded rats, and pancreatectomy was performed on another group of hooded rats. Eight to 16 days later, fluorescein sodium, 16.6 mg/kg, was injected in the femoral vein of 21 hyperglycemic rats and 18 normal animals. One hour later, the aqueous, vitreous, and plasma fluorescence levels were measured using fluorophotometry. We did not find a significant difference between vitreous fluorescence levels of the hyperglycemic streptozocin- and insulin-treated or non-insulin-treated and normal rats. Moreover, we did not find a significant difference between the vitreous fluorescence of hyperglycemic rats with pancreatectomy and normal rats.

Animals↗
PubMed1986

Impaired axonal transport of opiate and muscarinic receptors in streptozocin-diabetic rats.

Axonal transport of receptors was studied in streptozocin-diabetic rats using two different binding models. Streptozocin-induced hyperglycemia caused a reduced accumulation of muscarinic receptors above a ligature placed on rat sciatic nerves when the binding assay was performed in vitro with [3H]QNB. In the vagus nerve, the retrograde axonal transport of receptor-bound opiate was strongly decreased in the streptozocin-treated rats when [3H]lofentanil was used in vivo to label opiate receptors. Insulin partly reversed the changes observed in the streptozocin-treated rats. These findings suggest that impaired axonal transport of receptors may explain part of the neurological disturbance which is seen in diabetic patients.

Animals↗
PubMed1986

Definition of streptozocin toxicity for primary lymphoidal tissues.

Hyperglycemia was induced in BALB/c mice with either streptozocin or alloxan to evaluate the effects of these drugs on primary lymphoidal tissues. Streptozocin but not alloxan briefly inhibited in situ DNA synthesis in bone marrow and thymus, elicited a transient selective depletion of circulating lymphocytes, and elicited a transient selective depletion of cortical thymocytes. Streptozocin also inhibited in vitro DNA synthesis of bone marrow cells and thymocytes from normal mice. A single subdiabetogenic dose of streptozocin depleted circulating lymphocytes and thymocytes.

Alloxan↗
PubMed1976

Effect of streptozocin on gastrin release.

As streptozocin has a toxic effect on gastrin producing cells in some patients with gastrinomas, the action of the drug upon normal gastrin release was evaluated in patients with carcinoid tumours (n=6) and malignant insulinomas (n=2). No acute effects were recorded in 22 instances where gastrin levels were followed during the first 24 hours after infusion of streptozocin. When gastrin levels were compared throughout a course of repeated infusions during months a significant increase was noted. Concentrations were doubled after 6 g streptozocin given during a four months period, and tripled after 10 g in nine months period. One patients developed bleeding duodenal ulcer after a total dose of 6 g. It is concluded that streptozocin does not damage normal G cells, but by some action seems to stimulate gastrin relase. Peptic ulceration may be an important side effect during a long term treatment.

Adenoma, Islet Cell↗
PubMedDate not supplied

Caloric intake and hypothalamic neurotransmitters in Zucker rats made acutely diabetic with streptozocin.

Zucker rats, lean and obese, treated with low dose intraperitoneal injections of streptozocin become hyperglycemic within 24h. Insulin levels fall, although the obese animal remains hyperinsulinemic. Associated with these changes in glucose and insulin there are transient decreases in caloric intake. Macronutrient selection studies show that protein consumption decreases. There is a trend for fat intake to decrease. The levels of hypothalamic neurotransmitters in the lean animals are not altered by streptozocin. The levels of 5-hydroxyindoleacetic acid increases in the streptozocin-treated obese animal in the paraventricular region, ventromedial region and the raphe. Serotonin is also significantly increased in the paraventricular region of the obese rat. These results suggest that acutely, treatment with streptozocin injures pancreatic islets, causing, in turn, decreases in insulin levels so that hyperglycemia ensues in both phenotypes. Associated with these perturbations are decreases in caloric intake. The magnitude of change in insulin levels is much greater in the obese rat. It is hypothesized that in the obese Zucker rat decrements in food intake are mediated by increase in serotonin turnover in the hypothalamus and these changes are related to changes of insulin levels. These data support the concept that circulating insulin affects hypothalamic neurotransmitters.

Animals↗