Neoplastic Lesions in Streptozotocin-treated Rats

Okawa, Hitoshi; Doi, Kunio

doi:10.1538/expanim1978.32.2_77

Cited by 19 publications

(12 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this connection, there still remains the possibility that these changes might be an indication of a delayed type of renal toxicity of SZ as was suggested in rats (Rakieten et al, 1968;Okawa & Doi, 1983). The piled-up appearance of the epithelial cells might be due to tangential cutting of the deformed tubules caused by marked luminal dilatation rather than a true piling up of cells.…”

Section: Discussionmentioning

confidence: 89%

“…However, it is also known that SZ has acute toxic effects on many organs in some animal species (Levine et al, 1980) and leads to delayed-type renal toxicity in rats (Rakieten et al, 1968;Okawa & Doi, 1983). This suggests that full attention should be paid to histopathological changes in other organs as well as the pancreas when SZ-treated animals are used for studies on diabetes.…”

Section: Abstract: Mice; Streptozotocin; Diabetes Mellitus Experimenmentioning

confidence: 99%

See 1 more Smart Citation

Histopathology of streptozotocin-induced diabetic DBA/2N and CD-1 mice

Honjo

Doi

et al. 1986

Lab Anim

View full text Add to dashboard Cite

SummaryHistopathological examinations were carried out on femaie DBA/2N and CD·l mice which were autopsied 4 and 12 weeks after six daily intraperitoneal injections of streptozotocin (SZ). Histopathological changes related to SZ treatment were found in the pancreas, liver and kidneys. Little difference was observed between the two strains in the histological changes of the pancreas (a decrease in size of the islets, and degranulation and a decrease in the number of B cells) and liver (hypertrophy of hepatocytes and cytoplasmic invagination into hepatocyte nuclei). With regard to the changes in the kidneys, DBA/2N mice showed characteristic inclusions positive to periodic acid-Schiff reagent in the distal tubule epithelial cells, while CD-l mice showed remarkable luminal dilatation and epithelial cell deformation of distal tubules. SZ-induced diabetes had no innuence on the development of spontaneous cardiovascular lesions in DBA/2N mice under the present experimental conditions. Keywords: Mice; Streptozotocin; Diabetes mellitus, experimental; Pancreatic diseases; Liver diseases; Kidney diseasesStreptozotocin (SZ), which was originally developed as an antibiotic and antitumour agent, is now widely used to induce insulin-dependent diabetes mellitus in rodents because of its toxic action on islet B cells (Like et al., 1978). However, it is also known that SZ has acute toxic effects on many organs in some animal species (Levine et al., 1980) and leads to delayed-type renal toxicity in rats (Rakieten et al., 1968;Okawa & Doi, 1983). This suggests that full attention should be paid to histopathological changes in other organs as well as the pancreas when SZ-treated animals are used for studies on diabetes. There are only a few reports, however, on the systemic histopathology of SZ-induced diabetic animals (Arison et al., 1967) generally said that diabetes accelerates the progression of existing cardiovascular lesions in humans.In this paper we report the histopathology of the main organs in SZ-induced diabetic DBA/2N and CD-l mice and the influence of hyperglycaemia on the development of spontaneous cardiovascular lesions in DBAl2N mice (Doi et al., 1985;Maeda, Doi & Mitsuoka, 1986) up to 12 weeks after SZ treatment.Materials and methods 43 female DBA/2NCrj (DBA/2N) mice weighing 10-14 g each and 20 female CRJ:CD-l (CD-I) mice weighing 17-21 g each were obtained from Charles River Japan Inc., Atsugi, Kanagawa, at 4 weeks of age. The mice were housed in an animal room at a temperature of 23 ± 2°C with a relative humidity of 55 ± 5% and were fed CRF-l (Charles River Japan Inc.) and water ad libitum.At 5 weeks of age, 23 DBA/2N and 10 CD-l mice received SZ at 50 mg/kg of bodyweight per day for six consecutive days. SZ (Sigma Chemical Company, St. Louis, MO, USA) was dissolved in citrate buffer (pH 4·5) immediately before daily intraperitoneal injection. The remaining mice of each strain received citrate buffer alone in the same way and served as controls. Bodyweight and food and water intake for 24 h were measured weekly...

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Abstract: Mice; Streptozotocin; Diabetes Mellitus Experimenmentioning

confidence: 99%

Histopathology of streptozotocin-induced diabetic DBA/2N and CD-1 mice

Honjo

Doi

et al. 1986

Lab Anim

View full text Add to dashboard Cite

show abstract

“…The cytotoxic action of STZ is mediated by free radicals and STZ has toxic and carcinogenic effects on the pancreas, liver and kidneys [9].…”

Section: Introductionmentioning

confidence: 99%

<i>Ocimum Gratissimum</i> Linn Causes Dose Dependent Hepatotoxicity in Streptozotocin-Induced Diabetic Wistar Rats

Onaolapo

2012

Macedonian Journal of Medical Sciences

View full text Add to dashboard Cite

Aim: Hepatoprotective effects of Ethanolic extract Ocimum gratissimum leaves (O. gratissimum) in streptozotocin-induced diabetic rats was studied. Material and Methods:Thirty-six adult rats were assigned into six groups (A, B, C, D, E and F) of six rats each. Group A was the control, while diabetes was induced in groups B, C, D, E and F. Fasting blood glucose was determined and rats with blood glucose concentration >18.0 mmol/L were considered diabetic. Group A (non diabetic control) and F (diabetic control) received normal saline orally, group B received a Metformin at 25 mg/kg while groups C, D and E had O. gratissimum at 400, 600 and 800 mg/ kg. Treatment was daily for a period of 28 days for all groups. Fasting blood glucose was monitored weekly, serum levels of Alanine transaminase (ALT) and Aspartate transaminase (AST) were measured on day twenty eight. Animals were sacrificed, liver sections processed for histological study. Statistical analysis was carried out using a one way ANOVA followed by a post-hoc test.Results: Results showed reduction in blood sugar and increase in biochemical and histologic markers of hepatic injury. Conclusion:Ethanolic extract of O. gratissimum causes dose dependent hepatic injury despite its glucose lowering ability.

show abstract

“…As streptozotocin is a genotoxic compound of carcinogenic potential in rats [9,39], it has to be excluded as a relevant contributor to tumor formation in this model. In the late 1970s, some research groups investigated a similar experimental setting of combined streptozotocin treatment or pancreatectomy and islet transplantation [24,25,34], but these studies lacked important control groups and investigated only very few animals (n=10-25).…”

Section: Discussionmentioning

confidence: 99%

“…However, to the best of our knowledge, the influence of insulin on the proliferative activity of bile duct epithelia in vivo has not yet been investigated. On the other hand, streptozotocin that is widely used in islet transplantation studies in rats, to establish diabetes, is genotoxic and has carcinogenic potential [9,39]. Therefore, it is still not clarified whether insulin after islet transplantation or streptozotocin was responsible for the development of cholangiocellular lesions.…”

Section: Introductionmentioning

confidence: 99%

Cystic cholangiomas after transplantation of pancreatic islets into the livers of diabetic rats

Evert

Schildhaus²,

Schneider‐Stock

et al. 2006

Virchows Arch

View full text Add to dashboard Cite

Islet transplantation is increasingly used as a therapy for human type 1 diabetes mellitus. In our study, we investigated the effect of the transplantation of a low number (n = 350) of pancreatic islets into the right liver part on the neighboring portal bile ducts. Male streptozotocin- diabetic Lewis or autoimmune-diabetic BB/Pfd rats (n = 1065) were subdivided into 11 experimental groups. A few days after low-number islet transplantation, cholangiocytes adjacent to the grafts showed an increase in proliferative activity. During the next 12-24 months, many peri-insular ductules progressed via tumor-like cystic lesions to large cystic cholangiomas, accompanied by a translocation of the insulin receptor into the cytoplasm and an increase in expression of insulin-related signaling proteins (Insulin-receptor-substrate-1, Raf-1, Mek-1). After 24 months, 53% of rats with low-number transplantation exhibited at least one cholangioma >10 mm, significantly outnumbering tumor development in the transplant-free left liver part and in any control group. No cholangiocarcinomas emerged. A graft cell origin of the tumors was excluded by Y chromosome in situ hybridization in cross-gender transplantations. Conclusively, low-number intrahepatic islet transplantation, most likely acting by permanent local hyperinsulinism, leads to prolonged cholangiocellular proliferation in streptozotocin- and in autoimmune-diabetic rats, resulting in the development of benign cystic cholangiomas.

show abstract

Neoplastic Lesions in Streptozotocin-treated Rats

Cited by 19 publications

References 14 publications

Histopathology of streptozotocin-induced diabetic DBA/2N and CD-1 mice

Histopathology of streptozotocin-induced diabetic DBA/2N and CD-1 mice

<i>Ocimum Gratissimum</i> Linn Causes Dose Dependent Hepatotoxicity in Streptozotocin-Induced Diabetic Wistar Rats

Cystic cholangiomas after transplantation of pancreatic islets into the livers of diabetic rats

Contact Info

Product

Resources

About