Age- and Sex-Related Differences in Spontaneous Hemorrhage and Fibrosis of the Pancreatic Islets in Sprague–Dawley Rats

Abstract

To elucidate the spontaneous occurrence of hemorrhage in the pancreatic islet, naïve Crj:CD(SD)IGS rats were given a commercially available standard diet ad libitum over 20 weeks, and were sequentially examined. Islet hemorrhage was morphologically observed from 12 weeks of age, and its incidence was significantly higher in males than in females, with a wide distribution in all pancreatic lobes. The incidence (%) of affected islets to examined islets was increased with age. Hemorrhage was accompanied by brownish pigmentation, and reacted positively for iron by Prussian/Berlin blue staining. In 26 weeks old, most of the islets were dissected by dense fibrous tissue into small nests, and disarranged beta cells were detected by insulin immunostaining. Ultrastructurally, no apparent morphological change was seen in any islet endothelial cell, although blood leakage with migrated macrophages and dense collagen fibers was observed around the capillaries. In serum biochemistry of rats aged 26 weeks, the estradiol level in males with hemorrhage was significantly lower than that in males with non-hemorrhage, presumably suggesting the lack of capillary protective ability. Next, when rats were given a high fat/protein diet over 20 weeks to clarify whether it accelerated the frequency or timing of hemorrhage, its occurrence was essentially identical to that of the animals fed the standard diet. In conclusion, the onset of spontaneous islet hemorrhage was observed predominantly in aged males, resulting from the low estradiol level in serum.

Proceedings of the 2014 National Toxicology Program Satellite Symposium

“…These findings share some features with background acinar atrophy but, in this case, the islets were not spared, the inflammatory response was more severe, and the controls did not demonstrate a background change of acinar atrophy (McInnes 2012a). Islet hemorrhage and fibrosis has been reported as a background finding in older male SD rats that is similar morphologically to the peri-islet findings in this case (Imaoka et al 2007). However, the rats were young (16 weeks at the termination of study), there was extensive acinar involvement, and the controls did not have this change as a background finding.…”

Histological Observation of Islet Hemorrhage Induced by Diagnostic Ultrasound with Contrast Agent in Rat Pancreas

“…Islet hemorrhage, followed by inflammation and progressive fibrosis, has been found to occur with age in spontaneously diabetic rats [11]. This spontaneous hemorrhage and fibrosis can lead to reduced islet function [12]. In a rat model of type 2 diabetes, disruption of endothelium and intra islet hemorrhage has been observed as the disease progresses to islet failure [13].…”

Effects of Estradiol Treatment and/or Ovariectomy on Spontaneous Hemorrhagic Lesions in the Pancreatic Islets of Sprague-Dawley Rats

“…The number of animals that had any of these lesions in any of the three pancreatic parts was counted. To obtain the exact incidence of each individual lesion, the incidence (percentage) of the pancreatic islets that had the lesion was calculated in the total number of islets examined in the left pancreatic lobe of an individual rat, because no significant difference in incidence had been observed between the three pancreatic parts (Imaoka et al 2007). The individual incidence was used for calculation of the group mean incidence.…”

“…Recently, we have reported additional morphological changes, hemorrhage, inflammation, and the progress of islet lesions in SD rats aged from eight to twenty-six weeks (Imaoka et al 2007). The slightest change, such as leakage of red blood cells from the capillaries in the islets, is considered to be followed by hemosiderin deposition and/or infiltration of pigmentladen macrophages.…”