Streptozotocin-Induced Liver Damage in Mice

Abstract

Diabetes incidence and liver damage was studied and identified in C3H-s mice 21 days after Streptozotocin (SZ) administration (250 mg/kg/i.v.) at 04 hs (4 a.m.) and 16 hs (4 p.m.). Metabolic disturbances were assessed by daily control of glycosuria and serum glucose determined at the end of the experiment. Liver damage was controlled by light and electron microscopy. Both effects showed a circadian variation, with significant greatest values in the 16-h-injected group. Liver damage appeared whether the animals became diabetic or not, consisting in degranulation of the rough-surfaced endoplasmic reticulum, mitochondrial swelling with loss of cristae and edema of the ground substance, with flocculent amorphous precipitate. In some hepatocytes, a dilated cisternae of the endoplasmic reticulum was seen. It was concluded that: a) beta-cell and hepatocytes have a synchronic circadian sensitivity to SZ; b) liver damage was present whether the animals became diabetic or not, suggesting the presence of a different threshold for SZ effect in hepatocytes. These results might be taken into account when planning SZ use, either for experimental or clinical purposes.

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

“…The outer sides of these cell nuclei became irregular, and swellinglike lesions were also found in the nuclei. The fact that an enlargement (megalocytosis) was observed in hepatocytes and their nuclei in the livers of the experimental group on day 15 compared to day 3 was in line with the results of Laguens et al (25) and Doi et al (14). Unlike the lesions detected on day 3, cytoplasmic invaginations with intranuclear eosinophilic character and globular structure were frequently found, which is in line with the data of Can et al (21).…”

“…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.…”

Catecholamine-Induced cAMP Response in Streptozotocin-Induced Diabetic Rat Liver.

“…Surprisingly, the liver dysfunction in the blood chemistry was observed in all untreated diabetic rats. The liver dysfunction seems to be produced by streptozotocin-injection (Laguens et al 1980), and worsened by a diabetic state, because it was observed as early as 1 week after the injection, and was improved by insulin-treatment. The increased /3-adrenergic response has been reported in partially hepatectomized (Huerta-B ahena et al 1983) and cholestatic (Aggerbeck et al 1983) rat hepatocyte.…”

“…Recently, it was reported that isoproterenol-responsive adenyl cyclase was decreased to a half in the diabetic rat liver 15 days after streptozotocin-injection, and the authors explained their results as the duration and/or severity of the diabetic state (Shima et al 1992). The liver damage was found at 3 weeks after streptozotocin-injection (Laguens et al 1980). Therefore, changes in adenyl cyclase reported in the streptozotocininduced diabetic rat liver might not represent diabetic change itself.…”

Increased Epinephrine-Induced cAMP Response in Severely Diabetic BB/W Rat Liver.

“…But liver dysfunction was observed when streptozotocininjected rats were kept without insulin, as reported by Lauguens et al [10]. Enhanced f3-adrenergic response has been reported in partially hepatectomized [11] and cholestatic [12] rat hepatocytes.…”