Ameliorating effect of N-acetylcysteine on iron toxicity of the liver and pancreas in albino rats: histochemical and ultrastructural study

Iron overload is common with chronic liver disease. Iron supplementation in diabetes mellitus patients causes severe pancreatic damage. In our study we aimed to test the possible protective effects of N-acetylcysteine (NAC) on the iron toxicity of rat liver and pancreas. We divided thirty-two male albino rats into four groups, eight animals each. For four weeks the experimental animals were treated as follows: Group I (control group): rats received daily single intra-peritoneal injection of NaCl solution in equal volume to same amount of the iron injection; Group II (NAC-treated group): a dose of 300mg/kg of NAC was given to the rats of this group by oral gavage once daily; Group III (Iron-treated group): the rats of this group received intraperitoneal injection of iron in a dose of 100mg/kg, three times per week; Group IV (NAC and iron-treated group): the rats were treated daily with oral NAC administration in a dose of 300 mg/kg and intraperitoneal injection with iron in a dose of 100 mg/kg, three times per week. After four weeks of treatment, the experimental rats were anaesthetized and sacrificed, the blood was collected for biochemical analysis and the liver and pancreas organs were dissected for histopathological investigations and electron microscopic examination. Iron overload caused marked centrolobular hepatic vacuolization, impacted sinusoids with brownish hemosiderin pigment associated with single cell necrosis, and apoptosis in hepatic cells together with pancreatic acinar degeneration associated with marked interstitial hemosiderin deposition. Biochemical assay revealed elevated levels of serum iron, ferritin and iron binding capacity in the iron-treated rat group due to the resulting oxidative stress. The use of NAC plus iron reduced the iron toxicity on hepatic and pancreatic tissues, with marked decrease of hepatic vacuolization and decrease of hemosiderin sedimentation in the hepatic sinusoids with decreased pancreatic acinar degeneration and necrosis. The application of NAC in the protocol of therapy improved the serum iron, ferritin and total iron binding capacity levels in the experimental rats.