ABSTRACT
Alzheimer's disease attacks the brain causing gradual memory loss. Alzheimer's brain showed excess beta amyloid protein and neurofibrillary tangles, containing deposition of aluminium. Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer's. Inducible nitric oxide synthase [iNOS] derived nitric oxide [NO] has been implicated in this process of neuronal cell death and apoptosis. Aluminium is considered a potential etiological factor in Alzheimer's disease and was used to produce an animal model of Alzheimer's. However, the exact mechanisms of aluminium induced Alzheimer's and neurotoxicity remain largely unknown. The present study was carried out to investigate the profile of the expression of iNOS in the hippocampus in an animal model of Alzheimer's produced by aluminium administration. Twenty four adult male albino rats were divided equally into four groups. Group I was the untreated control, groups II, III and IV were given aluminium chloride [300 mg/kg body weight] orally daily for one week, two and four weeks, respectively. At the end of the experiment, rats were killed by decapitation under brief anaesthesia. The brains were removed and processed for immunohistochemistry using antibody raised against iNOS. Results: By comparison to the untreated control, aluminium treated rats showed significant [P<0.05] increase in the expression of iNOS in the hippocampus. The expression was mainly neuronal and was seen in all areas. Additionally. administration of aluminium for four weeks caused marked histological changes with significant [P <0.05] reduction in hippocampus neuronal number and distortion of neuronal morphology. These data provide further evidence that exposure to aluminium may contribute to pathogenesis of Alzheimer 's and neurotoxicity by induction ofiNOS with subsequent increase in NO production that potentiate neuronal cell death in hippocampus
Subject(s)
Male , Animals, Laboratory , Alzheimer Disease , Nitric Oxide Synthase , Hippocampus/physiology , Up-Regulation/drug effects , RatsABSTRACT
Heme oxygenase [HO] is the rate-limiting enzyme in the catabolism of heme to biliverdin, iron and carbon monoxide. Two isoforms of HO have been characterized: the constitutive isoform [HO-2], the major isoform present under physiological conditions, and the stress-induced isoform [HO-1], which is also known as heat shock protein. In this study 15 liver biopsies from patients with cirrhosis secondary to hepatitis B and C and 5 biopsies from healthy controls were investigated for the expression of HO-1 and HO-2 protein using a standard immunohistochemical method. In normal liver, HO-1 immunoreactivity was seen in Kupffer cells. In cirrhotic liver, increased HO-1 immunoreactivity was seen in Kupffer cells, the endothelial lining of portal vein and hepatic sinusoids, and to a lesser extent, in hepatocytes. In Kupffer cells, dense perinuclear HO-1 reactivity was seen, whereas in hepatocytes HO-1 reactivity was weak and diffuse throughout the cytoplasm. By comparison with control tissues, only HO- 1 showed significant increase immunoreactivity in cirrhotic liver [p<0.04] On other hand, HO-2 immunoreactivity was seen only in hepatocytes in both control and cirrhotic livers. This result shows that in liver cirrhosis, HO-1 expression is increased significantly and is seen preferentially in Kupffer cells. This suggests that Kupffer cells may act as sensory cells that detect the elevation of intrasinusoidal pressure accompanying hyperdynamic states secondary to portal hypertension, implicating an increase in regional wall stress in sinusoids and thereby alter the ability of Kupffer cells to degrade heme through HO-1 induction. Another mechanism by which HO- 1 could be upregulated in liver cirrhosis is via nitric oxide, and we have previously shown high expression of NO in liver cirrhosis. This study suggests a role for HO- 1 in the development of ci1Thosis in viral hepatitis and points out the need for additional work in this area