ABSTRACT
Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Agents, Hormonal/toxicity , Iron/metabolism , Liver/drug effects , Liver/metabolism , Tamoxifen/pharmacology , Tamoxifen/toxicity , Animals , Antineoplastic Agents, Hormonal/therapeutic use , Blood Glucose/metabolism , Breast Neoplasms/drug therapy , Diabetes Mellitus, Experimental , Female , Humans , Liver/cytology , Random Allocation , Rats , Rats, Wistar , Tamoxifen/therapeutic useABSTRACT
PURPOSE: A comparison was done between the F. Paulino jejunal pouch (FP) and a jejunal pouch (JP) as esophagus-duodenum interpositional graft, for replacing the stomach after total gastrectomy. It was investigated the effect of the two procedures on esophagus histology, nutritional state and serum gastrin in rats. METHODS: Male Wistar rats weighing 282 +/- 17g were randomly submitted to sham operation (S), FP and JP after total gastrectomy. After eight weeks the rats were killed with overdose of anesthetic and tissue was taken from the distal esophagus for histology. Serum levels of total proteins, albumin, iron, transferring, folate, cobalamine, calcium, as well as serum gastrin were determined. Survival was considered. RESULTS: Fourty six rats were operated and thirty survived for eight weeks. Five (33.3%) died after FP and 11 (52.3%) after JP (p < 0.05). Postoperative esophagitis occurred in 6 JP rats. At 8th week, no difference was observed on body weight when compared FP and JP rats (p > 0.05). The JP rats had a significant decrease in serum albumin, glucose, transferrin, iron, folate and calcium, compared to sham (p < 0.05). Serum gastrin, iron and calcium were significantly higher in JP rats than in FP rats (p < 0.05). In FP rats, transferrin and cobalamine showed significant decrease comparing the preoperative with 8th week levels (p < 0.05). CONCLUSION: F. Paulino pouch in rats had lower mortality than JP, and esophagitis was not detected in it. JP rats had serum gastrin, iron and calcium unaffected, possibly because of preservation of duodenal passage.
