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

Abstract

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...

Antidiabetic Activity of Polyherbal Formulation in Streptozotocin – Nicotinamide Induced Diabetic Wistar Rats

“…The hepatic changes may be due to the hypertrophy of hepatocytes by an increase in the intracytoplasmic eosinophilic granules. [36] Polyherbal formulation and glibenclamide treatment to the animals reduced the severity of the histopathologic changes caused by STZ.…”

Functional photoacoustic microscopy of diabetic vasculature

“…STZ is specifically toxic to the beta cells of the pancreas, reducing the amount of insulin available to the animal; its administration is an established method for inducing insulin-dependent (type 1) diabetes in mice. 10 PAT is particularly well-suited for measuring changes in diabetic vasculature because it can monitor vessel-by-vessel changes in diameter, sO 2 , blood flow speed, and total hemoglobin concentrations.…”

Immunohistochemical localization of glutathione peroxidase 1 enzyme and its gene expression by RT-PCR in the liver tissue of healthy and diabetic mice

“…While some researchers developing diabetes in mice using STZ (14,25) noted that the hepatocyte nucleus area increased, some (25,26) reported that the size of the cell increased (hypertrophy). Honjo et al (26) revealed that cytoplasmic invaginations formed in the hepatocyte nucleus. Doi et al (14) reported that the hepatocyte nucleus area in STZ diabetic mice was nearly twice as large as the controls and showed irregular structures.…”

“…Watkins et al (17), who examined the livers of STZ diabetic mice at the electron microscopic level, reported swelling in the hepatic sinuses, especially on the first and third days, and a visible enlargement between hepatocyte boundaries. While some researchers developing diabetes in mice using STZ (14,25) noted that the hepatocyte nucleus area increased, some (25,26) reported that the size of the cell increased (hypertrophy). Honjo et al (26) revealed that cytoplasmic invaginations formed in the hepatocyte nucleus.…”