[Show abstract][Hide abstract] ABSTRACT: The 4,4'-diketo-beta-carotene, canthaxanthin, alters tocopherol status when fed to Balb/c mice, suggesting an involvement of carotenoids in the modulation of oxidative stress in vivo. We investigated further the modifications induced by an oral administration of canthaxanthin on lipid peroxidation, antioxidant enzymes and iron status in liver of Balb/c mice. Female 6-wk-old Balb/c mice were randomly divided into two groups (n = 10/group). The control group (C) received olive oil alone (vehicle) and the canthaxanthin-treated group (Cx) received canthaxanthin at a dose of 14 microg/(g body wt.d). The 15-d canthaxanthin treatment resulted in carotenoid incorporation but did not modify lipid peroxidation as measured by endogenous production of malondialdehyde (MDA). However, glutathione peroxidase activity was 35% lower (P<0.01) and catalase (59%, P<0.005) and manganese superoxide dismutase (MnSOD) (28%, P<0.05) activities were higher in canthaxanthin-treated mice than in controls. Moreover, carotenoid feeding caused a significant (P<0.05) overexpression of the MnSOD gene; mRNA levels of the enzyme were greater in treated mice than in controls. Concomitantly, a 27% (P<0.05) greater iron concentration was found in liver from canthaxanthin-treated mice compared with controls. These findings support the hypothesis that canthaxanthin alters the protective ability of tissues against oxidative stress in vivo.
Preview · Article · May 2000 · Journal of Nutrition
[Show abstract][Hide abstract] ABSTRACT: In order to investigate the pathogenic mechanism responsible for liver injury associated with chronic alcoholism, we studied the effects of different dietary vitamin E levels in chronically ethanol (EtOH)-fed rats on the activity and mRNA regulation of the manganese superoxide dismutase (MnSOD) enzyme. Evidence is accumulating that intermediates of oxygen reduction may in fact be associated with the development of alcoholic liver disease. Since low vitamin E liver content seems to potentiate EtOH-linked oxidative stress, we studied the effect of EtOH treatment in livers from rats fed a diet deficient or supplemented with vitamin E. Chronic EtOH feeding enhanced hepatic consumption of vitamin E in both groups of EtOH-treated animals, irrespectively of the vitamin E level of the basal diet and the effect was observed in both the microsomal and mitochondrial fractions. Both EtOH-fed groups exhibited increased MnSOD gene expression, while the enzyme activity was enhanced only in the vitamin E-deprived group of EtOH-treated animals. The significant increase in manganese liver content found only in this last group could explain the rise of enzyme activity. In fact, in the absence of a parallel increase of the prosthetic ion manganese, MnSOD mRNA induction was not accompanied by a higher enzymatic activity. These findings support the role of oxidative alteration in the EtOH-induced chronic hepatotoxicity in which MnSOD response might represent a primary defence mechanism against the damaging effect of oxygen radical species.
No preview · Article · Mar 2000 · Alcohol and Alcoholism
[Show abstract][Hide abstract] ABSTRACT: Substantial evidence supports the hypothesis that oxygen free radicals are involved in various neurodegenerative disorders. To assess the presence of oxidative stress in Alzheimer's disease (AD) we examined the activity of the enzyme copper-zinc superoxide dismutase (CuZnSOD) in red blood cells, the levels of the mitochondrial inducible enzyme manganese superoxide dismutase (MnSOD) mRNA in lymphocytes, and the total radical-trapping antioxidant capacity (TRAP) in plasma of AD patients and in a group of age-matched non-demented controls. We found that CuZnSOD activity (P < 0.01 vs. controls) was significantly increased as well as the MnSOD mRNA levels while the total antioxidant status (P < 0.001 vs. controls) was decreased in AD patients. These findings support the role of oxidative alterations in the pathogenetic mechanism underlying AD neurodegeneration.
No preview · Article · Jul 1998 · Neuroscience Letters
[Show abstract][Hide abstract] ABSTRACT: The oxy-radical scavenger enzyme manganese superoxide dismutase (MnSOD) may act in the capacity of a tumour-suppressor gene. To address the issue of its role in tumour transformation and progression in vivo, we evaluated the content of this enzyme in 33 brain tumours of neuroepithelial origin with different degrees of differentiation (WHO grade II-IV) by means of Western blot and immunohistology. Our results show that immunoreactive MnSOD increases in a direct relationship with tumour grade and is therefore inversely correlated with differentiation. The increase in induced at a pretranscriptional level and is apparently specific to brain tumours of neuroepithelial origin. Approximately 30% of grade IV tumours display low levels of MnSOD content, and preoperative radiotherapy and brachytherapy result in low amounts of enzyme. Based upon these observations, we suggest that MnSOD cannot be considered a classical tumour-suppressor gene.
Full-text · Article · Jan 1997 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: On the basis of the well-known effect of ethanol poisoning on the prooxidant/antioxidant balance of human and rodent liver we tested the response of the mitochondrial manganese-containing superoxide dismutase (MnSOD) in the liver of rats following an acute ethanol load or chronically intoxicated with an alcohol-supplemented solid diet for three weeks. In both conditions the enzyme activity and messenger RNA were monitored. In the acutely treated animals MnSOD was induced (post-)translationally already at 3 hours after ethanol injection, reached the maximum level (about 50% increment) at 9 hours and decreased thereafter. Chronic ethanol feeding caused an up-regulation of the enzyme at the mRNA level, with a good correlation between the transcript and the enzyme activity during the first two weeks of treatment. After 20 days the mRNA level dropped to normal, whereas the activity still remained high. Chronic alcohol intake also led to a significant decrease in the content of vitamin E in the liver mitochondrial and microsomal fractions, suggesting the occurrence of an enhanced lipid peroxidation, consequent to the ethanol-induced oxidative stress. The response of MnSOD appears to be a protective mechanism that the genetic machinery builds up to partially overcome such a condition.
No preview · Article · Jul 1994 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: Reactive oxygen species (ROS) have been frequently implicated in the initiation and promotion phases of carcinogenesis. Antioxidant enzymes, which can antagonize this process, are lowered in a number of malignancies. The enzyme most commonly decreased is the mitochondrial Mn-containing superoxide dismutase (MnSOD) encoded by a nuclear gene mapped on the band 6q21, a region frequently deleted in several human tumours. The close association of del(6q) with diminution of MnSOD has led to suggest that MnSOD might be a new type of tumour-suppressor gene. This hypothesis is also sustained by the finding that transfection of MnSOD cDNA into human melanoma cell lines suppress the malignant phenotype. There are, however, conflicting observations that tend to ascribe the deficiency of the MnSOD activity more to a defect in the expression of the gene than to its deletion. In many transformed cell lines, including some with marked del(6q), there is no change in the dosage of the MnSOD gene and the enzyme is highly inducible by various pro-oxidant agents. Transition metals (Mn, Fe) have been found to be highly deficient in human and rodent tumours. Owing to the second messenger function of ROS in activating transcription factors (NF-kB, AP-1) and to the ability of Mn to facilitate the dismutation of O2- to H2O2 and of Fe to participate in the Fenton reaction, we propose that in the early stage of carcinogenesis an impairment of the signal transduction machinery, related to the metal deficiency, might limit the binding to DNA of transcription factors and cause the defect in the MnSOD gene expression.
No preview · Article · Feb 1993 · Molecular Aspects of Medicine
[Show abstract][Hide abstract] ABSTRACT: Evidence is reported that liver manganese deficiency, whether artificially produced by the administration of a Mn-deficient diet, or physiologically occurring in the neonatal life, in mice and rats respectively, causes the down-regulation of the manganese-containing superoxide dismutase at (pre)-transcriptional level. These observations, in addition to previous data concerning Mn-deficiency and the low level of expression of MnSOD in Morris hepatomas, strongly support the role played by the metal ion in the control of the MnSOD by a mechanism of gene activation. While the molecular events taking place in such regulation are not yet identified, the involvement of reactive oxygen species (ROS) as second messengers in the activation of specific transcription factors is suggested.
No preview · Article · Jan 1993 · Biochemistry international