Protective effect of 17Beta-estradiol on oxidative stress and liver dysfunction in aged male rats

In aging liver oxidative stress increases due to the decrease in antioxidant bio-moleculessuch as estrogens which can be modified by hormonal replacement therapy(HRT). With this in mind, we hypothesized that age-related decline in steroidogenesismay be associated with the impairment of the antioxidant defense cells in liver,the increase in lipid peroxidation, hepatic dysfunction and histological changes;estrogens prevent all these changes induced by aging. 17â-estradiol treatment wasinitiated in 12 month-old Wistar rats, and continued until 18 months of age. Ourresults showed that 17Beta-estradiol (E2) level in the serum of the aged untreated ratswas reduced by –32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase(GPX) activities were reduced by –47, –46, and –29% respectively in old ratliver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasmasuch as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well asbilirubin level increased significantly in old rats, and histological changes were investigated.In E2-treated rats, protective effects were observed. Indeed, 17Beta-estradiolattenuates all changes induced by aging. The 17Beta-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activitieswere higher by +28, +15, and +11% respectively. This anti-aging effect of estrogenswas clarified by a lower level of lipid peroxidation and liver dysfunction parametersas well as by histological observation (AU)

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Protective effect of 17â-estradiol on oxidativestress and liver dysfunction in aged male rats

In aging liver oxidative stress increases due to the decrease in antioxidant bio-moleculessuch as estrogens which can be modified by hormonal replacement therapy(HRT). With this in mind, we hypothesized that age-related decline in steroidogenesismay be associated with the impairment of the antioxidant defense cells in liver,the increase in lipid peroxidation, hepatic dysfunction and histological changes;estrogens prevent all these changes induced by aging. 17â-estradiol treatment wasinitiated in 12 month-old Wistar rats, and continued until 18 months of age. Ourresults showed that 17â-estradiol (E2) level in the serum of the aged untreated ratswas reduced by –32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase(GPX) activities were reduced by –47, –46, and –29% respectively in old ratliver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasmasuch as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well asbilirubin level increased significantly in old rats, and histological changes were investigated.In E2-treated rats, protective effects were observed. Indeed, 17â-estradiolattenuates all changes induced by aging. The 17â-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activitieswere higher by +28, +15, and +11% respectively. This anti-aging effect of estrogenswas clarified by a lower level of lipid peroxidation and liver dysfunction parametersas well as by histological observation (AU)

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Protective effect of 17beta-estradiol on oxidative stress and liver dysfunction in aged male rats.

In aging liver oxidative stress increases due to the decrease in antioxidant bio-molecules such as estrogens which can be modified by hormonal replacement therapy (HRT). With this in mind, we hypothesized that age-related decline in steroidogenesis may be associated with the impairment of the antioxidant defense cells in liver, the increase in lipid peroxidation, hepatic dysfunction and histological changes; estrogens prevent all these changes induced by aging. 17beta-estradiol treatment was initiated in 12 month-old Wistar rats, and continued until 18 months of age. Our results showed that 17beta-estradiol (E2) level in the serum of the aged untreated rats was reduced by -32% in 18 month-old rats compared to the young animals (4-month-old). The superoxide dismutase (SOD), catalase (CAT), and gluthatione peroxidase (GPX) activities were reduced by -47, -46, and -29% respectively in old rat liver. In addition, the TBARs in liver and hepatic dysfunction parameters in plasma such as gamma-glutamyl transferase (GGT), phosphatase alkalin (PAL) as well as bilirubin level increased significantly in old rats, and histological changes were investigated. In E2-treated rats, protective effects were observed. Indeed, 17beta-estradiol attenuates all changes induced by aging. The 17beta-estradiol level was higher in old E2-treated rats compared to the control rats. Moreover, the SOD, CAT and GPX activities were higher by +28, +15, and +11% respectively. This anti-aging effect of estrogens was clarified by a lower level of lipid peroxidation and liver dysfunction parameters as well as by histological observation.

[Myelodysplastic syndrome / acute myeloid leukemia with t(8; 21) and bundle of Auer rods in neutrophils: an unusual hemopathy]. / Syndrome myélodysplasique / leucémie aiguë avec t(8;21) et polynucléaires à corps d'Auer en fagot: une hémopathie rare de présentation inhabituelle.

We report the case of a 8-year-old girl diagnosed with myelodysplastic syndrome. This case was morphologically characterized by the presence of bundle of Auer rods in the neutrophils. The evolution of the disease was marked by a quick transformation in a acute myeloid leukaemia with t(8;21) refractory to treatment. We reviewed the literature for clinical, biological and therapeutic features of this rare childhood hemopathy.

[Lipid profile in maintenance haemodialysis]. / Profil lipidique dans l'insuffisance rénale chronique au stade d'hémodialyse.

INTRODUCTION: The chronic kidney failure is a source of dyslipidemia and accelerated atherosclerosis. No changes in the lipoprotein profile could be reversed by dialysis. OBJECTIVE: Our aim was to study the lipid disturbances characteristics in end stage renal disease in order to assess their theorical atherogenic potential. SUBJECTS AND METHODS: The patient population consisted of 36 patients on maintenance haemodialysis. Matched control subjects were recruited among apparently healthy normolipidemic Tunisians. Total cholesterol, triglycerides, high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B concentrations were measured. RESULTS: The triglycerides levels were significantly higher in patient group, unlike the high-density-lipoprotein cholesterol and apolipoprotein AI levels that were significantly reduced. We saw no increase in the levels of low-density-lipoprotein cholesterol and apolipoprotein B. The low-density-lipoprotein cholesterol/high-density-lipoprotein cholesterol ratio result wasn't helpful in the evaluation of the atherogenic risk. CONCLUSION: We confirm the quantitative lipid disorders associated with maintenance haemodialysis. The assessment of cardiovascular risk on the basis of these disorders seems difficult.

Karyomegaly of tubular cells as early stage marker of the nephrotoxicity induced by ochratoxin A in rats.

Cases of karyomegaly were described by Sclare and by Mihatch in patients affected with tubular-interstitial nephropathy. The Karyomegalic cells showed enlarged nuclei with accumulation of genetic material. No aetiology was suggested. Our study of rats experimentally intoxicated by ochratoxin A, a well-known nephrotoxic compound, indicates the presence of karyomegaly with alteration of the tubular tissue. In control animals no karyomegalic cells were detected. These observations suggest that karyomegaly with megacytosis may be caused by the nephrotoxic ochratoxin A in the kidney. In addition abnormal mitosis together with karyomegalic cells were observed at an earlier stage of the intoxication (30 days) suggesting possible regeneration if the OTA insults are stopped. After 90 days of treatment, the degeneration increased and only karyomegalic and apoptotic-like cells were observed indicating that the regeneration no longer occurs and that the degeneration becomes irreversible.

Induction of a SOS repair system in lysogenic bacteria by zearalenone and its prevention by vitamin E.

Zearalenone (Zen) is an oestrogenic mycotoxin produced by several Fusarium species in cereals. It induces modifications of haematological parameters in rats with cytotoxicity and inhibition of macromolecular synthesis (nucleic acids and protein). Zen and its metabolites have oestrogenic and anabolic activities and interact with human oestrogen receptors. Zen and its metabolites showed a positive DNA damaging effect in recombination tests with Bacillus subtilis. It induces sister chromatid exchange and chromosomal aberration in CHO cells. Zen was found to be capable of inducing DNA-adduct formation in mouse liver. The genotoxicity of Zen was questionable until the last decade when increasing data tended to show this toxin to be genotoxic in vivo. However the mechanism of its genotoxicity and mutagenicity has not been completely clarified. The present investigations were designed to show whether Zen induces an SOS-DNA repair response in lysogenic bacteria which have an integrated lambda-bacteriophage in their genome. Zen was found to be genotoxic in the bacterial systems from a concentration of 1.50 mM and it was also bactericidal (IC50 = 1.45 mM). In addition vitamin E (6.0-12.0 mM) added 1 h prior to the toxin proved to prevent both the genotoxic and bactericidal effects of Zen. This vitamin could be active both as an antioxidant and as a radical scavenger. The specificity of this prevention is probably due to the similarity of structure between vitamin E and Zen.

Zearalenone induces modifications of haematological and biochemical parameters in rats.

Zearalenone produced by the fungus Fusarium roseum causes important perturbations in the gestation cycle of the rat with hormonal disorders and infertility. In order to find out other eventual toxic effects, female rats were given intraperitoneally (i.p.) (1.5, 3 and 5 mg/kg) zearalenone in sterile olive oil. Forty-eight hours later, some blood parameters changed (hematocrit, MCV, the number of platelets and WBC) as well as some biochemical markers such as aminotransferases (ALT, AST), alkaline phosphatase (ALP), serum creatinine, bilirubin, indicating liver toxicity, and likely impairment of blood coagulation process.

[Reduction of lipoproteins with apoAI but without apoAII (LpAI) in non-insulin-dependent diabetic patients]. / Réduction des lipoprotéines avec apoAI mais sans apoAII (LpAI) chez les diabétiques non insulino-dépendants.

Recent data suggest the existence of a relationship between ischemic heart diseases and apolipoprotein A-I containing lipoproteins. The latter and other classic lipid-lipo-protein-apoprotein parameters were quantified in 25 non-insulin-dependent diabetics and 26 normoglycemic normolipidemic subjects. Compared to a control group, non-insulin-dependent diabetics have higher levels of plasma cholesterol (p < 0.05), triacylglycerol, apolipoprotein B (p < 0.001). In contrast, their lipoprotein particles containing only apolipoprotein AI without apolipoprotein AII and apoAI/apoB ratio were lowered (p < 0.001). In our diabetics, apolipoprotein AI was found at normal level but its distribution between high density lipoproteins ('HDL') and 'non-HDL' was abnormal. Also, the distribution of particles containing apolipoprotein A-I without apolipoprotein A-II in non-insulin-dependent diabetics was found abnormal. A higher proportion of both apoAI and LpAI were found in the 'non-HDL' fraction. These data show that lipoprotein metabolism is affected in non-insulin-dependent diabete mellitus. The disease is associated to a lipoprotein profile which is in favour of the atherogenic process.

Ochratoxin A in human blood in relation to nephropathy in Tunisia.

The determination of ochratoxin A (OTA) in human blood in Tunisian populations is underway. The range of contamination is between 0.7 to 7.8 ng ml-1 for the general population and 12 to 55 ng ml-1 for people suffering from chronic renal failure. It appears that 21 to 64% of people suffering from nephropathy are OTA positive with a detection limit of 1ng ml-1. This situation prompted us to search for possible association of OTA contamination and nephropathy resembling Balkan endemic nephropathy. The classification of the ill population into chronic interstitial nephropathy (CIN), chronic glomerular nephropathy (CGN), chronic vascular nephropathy (CVN) and others, indicated that the largest is the CIN group which is significantly different from the other groups, and from the control (P < 0.005). Furthermore, it presented the highest OTA mean values (25 to 59 ng ml-1) compared with the control, CGN, CVN and other groups (6 to 18 ng ml-1) according to the designated region in Tunisia. The rural population seems to be more exposed to ochratoxins in Tunisia, as has been previously reported in the Balkans and Western Europe. Altogether, these results emphasise that in Tunisia an endemic ochratoxin-related nephropathy is probably occurring.

Foodstuffs and human blood contamination by the mycotoxin ochratoxin A: correlation with chronic interstitial nephropathy in Tunisia.

Ochratoxin A (OTA) has been detected in high amounts in human blood samples collected in nephrology departments in Tunisia from nephropathy patients under dialysis, especially those categorised as having a chronic interstitial nephropathy of unknown aetiology. These represent 12-26.1% of all chronic renal failure patients. To clarify the situation, food and blood samples were collected from nephropathy patients and controls, (with no familial case of nephropathy). The OTA assay showed very different scales of OTA food and blood contamination from 0.1 to 16.6 micrograms/kg and 0.1-2.3 ng/ml, respectively, in controls and healthy individuals and 0.3-46 830 micrograms/kg for food and 0.7-1136 ng/ml for blood in nephropathy patients. The disease seems related to OTA blood levels and food contaminations, since the control group was significantly different from the nephropathy group (p < 0.005) for both food and blood ochratoxin A contamination. Combined with data published already, the results emphasize the likely endemic aspect of this OTA-related nephropathy occurring in Tunisia and possibly in other countries of northern Africa. This nephropathy is very similar to Balkan endemic nephropathy.

[Ochratoxin A genotoxicity, relation to renal tumors]. / Génotoxicité de l'ochratoxine A, relation avec la tumeur rénale.

Ochratoxin A (OTA) is a mycotoxin which has been implicated in Balkan Endemic Nephropathy (BEN), a disease characterized by tubulonephritis and may be involved in the high incidence of urinary tract tumors associated to BEN. The prevalence of human ochratoxicosis is being determined in Tunisia. 100% of people suffering from chronic interstitial nephropathy of unknown etiology were ochratoxin A positive. These nephropathies are similar to Balkan Endemic Nephropathy. We prove an OTA genotoxic effects in patient suffering from this kind of nephropathy. OTA-DNA adducts formation has been detected in DNA of kidney tissues (biopsy). DNA adducts which are covalent complex between OTA and DNA base (Guanine), constitute first steps of the carcinogenesis process.

Peptidoglycan adjuvants: minimal structure required for activity.

The chemical structure of the adjuvant active fraction of mycobacterial cell walls has been investigated. It had been shown previously that soluble peptidoglycan fragments obtained from cell walls of Mycobacteria by lysozyme digestion or by other treatments act as adjuvants for increasing both humoral and cellular immunity. We then found that even the monomer subunit of the peptidoglycan of Mycobacteria (i.e. a disaccharide-tetrapeptide) is adjuvant active; then, similar compounds from other strains of bacteria were tested; the monomeric subunits of meso-diaminopimelic acid as well as L-lysine containing peptidoglycans were found to be adjuvant active. The smallest active compound studied so far is N-acetyl-muramyl-L-alanyl-D-isoglutamine synthesized for us by SINAY et al. (1975).