Abstract
Purpose. This study evaluated the long-term effects of alloxan-induced diabetes in rat liver. Methods. Thirty nondiabetic control rats (NC) and 30 untreated diabetic (UD) rats were divided into three subgroups sacrificed after 6, 14, or 26 weeks. Clinical and laboratory parameters were assessed. Fresh liver weight and its relationship with body weight were obtained, and liver tissue was analyzed. Results. UD rats showed sustained hyperglycemia, high glycosylated hemoglobin, and low plasma insulin. High serum levels of AST and ALT were observed in UD rats after 2 weeks, but only ALT remained elevated throughout the experiment. Fresh liver weight was equal between NC and UD rats, but the fresh liver weight/body weight ratio was significantly higher in UD rats after 14 and 26 weeks. UD rats showed liver morphological changes characterized by hepatic sinusoidal enlargement and micro- and macrovesicular hepatocyte fatty degeneration with progressive liver structure loss, steatohepatitis, and periportal fibrosis. Ultrastructural changes of hepatocytes, such as a decrease in the number of intracytoplasmic organelles and degeneration of mitochondria, rough endoplasmic reticulum, and nuclei, were also observed. Conclusion. Alloxan-induced diabetes triggered liver morphological and ultrastructural changes that closely resembled human disease, ranging from steatosis to steatohepatitis and liver fibrosis.
Highlights
An association between type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which describes a wide spectrum of liver disorders from steatosis to cirrhosis, has long been recognized [1,2,3]
Much attention was given to this entity in patients with T2DM, but little is known about the evolution of liver injury in patients with type 1 diabetes mellitus (T1DM)
untreated diabetic (UD) rats without hyperglycemia treatment progressed to a severe loss of body weight and significant increase in water and food intake and urine output compared to nondiabetic control rats (NC) rats (P < 0.001)
Summary
An association between type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which describes a wide spectrum of liver disorders from steatosis to cirrhosis, has long been recognized [1,2,3]. Due to the short follow-up of animals, much of the published experimental research on T1DM could not define clearly whether observed histopathological liver injuries were the result of toxic effects of ALX or SZ or linked to the drug-induced diabetic hyperglycemic state [7,8,9,10,11,12,13]. This study evaluated whether T1DM induced by ALX could cause morphological and ultrastructural changes in rat liver to characterize the effects of this drug and diabetes for a longer follow-up period. We hope that our results can have reproduced a suitable experimental model for the investigation of diabetic chronic liver disease
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