María del Carmen Ada Contini
, Santa Fe de la Vera Cruz

Physiology, Nutritional Biochemistry, Biochemistry



  • María Del Carmen Contini · Néstor Millen · Marcela González · Adriana Benmelej · Ana Fabro · Stella Mahieu
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    ABSTRACT: The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats. © The Author(s) 2015.
    Toxicology and Industrial Health 01/2015; DOI:10.1177/0748233714566876 · 1.86 Impact Factor
  • Marcela Aida González · María Del Carmen Contini · Nestor Millen · Stella Teresita Mahieu
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    ABSTRACT: The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na(+) /K(+) ATPase activities in whole plasma membrane were determined. PH decreased the Na(+) /K(+) ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na(+) /K(+) ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier. Copyright © 2012 John Wiley & Sons, Ltd.
    Cell Biochemistry and Function 12/2012; 30(8). DOI:10.1002/cbf.2855 · 2.01 Impact Factor
  • María del Carmen Contini · Néstor Millen · Marcela González · Stella Mahieu
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    ABSTRACT: This study is designed to determine the simultaneous effect of aluminium (Al) and melatonin (Mel) treatment in intact and ovariectomized (Ovx) female rats on oxidative stress and their inter-organ relationship in the kidney and liver. Al-treated rats received an intra-peritoneal injection of solution of aluminium lactate (0.575 mg Al/100 g of body weight, three times a week), during 12 weeks. Mel groups received intra-peritoneal injections of melatonin at a dose of 10 mg/kg/day, 5 days/week, during 12 weeks. The results of this study showed that Al treatment in female rats modifies homeostasis of glutathione and the antioxidant capacity of the rat liver and kidney. The alteration of glutathione homeostasis and oxidative status was not associated with an increased lipid peroxidation in both organs with the exception of the increase observed in the liver of Ovx rats. Al also induced modifications in the activity of some enzymes related to the glutathione cycle: GSH-Px in the liver and kidney and glutathione reductase only in the kidney. Al exposure decreased CAT activity in both the kidney and liver of intact and Ovx groups. The administration of Mel in the intact and castrated females treated with Al seems to reduce oxidative changes in the liver and kidney of intact and Ovx rats.
    Biological trace element research 05/2011; 144(1-3):924-43. DOI:10.1007/s12011-011-9060-7 · 1.75 Impact Factor
  • Stella Mahieu · María del Carmen Contini · Marcela González · Néstor Millen
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    ABSTRACT: We evaluated the effect of melatonin (Mel), in male Wistar rats which received aluminium (Al) lactate for 12 weeks (0.57 mg Al/100g body weight (b.w.), i.p. three times per week). Moreover rats received Mel (10 mg/kg b.w. i.p. 5 days/weeks) for 12 weeks. At the end of the treatment water and sodium balances were studied, and nephrogenic cyclic adenosine monophosphate (cAMP) was also measured. Urinary osmolality was measured after the administration of desmopressin (vasopressin agonist) to assess concentrating capacity. Oxidative stress in renal tissue and Na(+)-K(+)ATPase and gamma-glutamyl transferase (GGT) activities in whole plasma membrane were determined. Sodium and water balances were impaired by Al. We found decreased urinary concentrating ability and nephrogenic cAMP excretion. Al increased the Na(+)-K(+)ATPase activity, and serum aldosterone concentration. Mel normalized serum aldosterone level, the Na(+)-K(+)ATPase activity and potassium urinary without improving water and sodium excretion. Mel treatment did not improve the impaired urinary concentrating ability. Al reduced the GGT activity, an effect that persists in Al(+) Mel. Al exposure promoted oxidative stress with an increase in lipid peroxidation (LPO), and a decrease in glutathione (GSH) and glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Mel markedly attenuated oxidative stress produced by Al. This may result from the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. However, it only reduced some alterations in the renal functions particularly related to the water and sodium excretion, which would be independent of the increased production of reactive oxygen substances.
    Toxicology Letters 07/2009; 190(1):9-15. DOI:10.1016/j.toxlet.2009.06.852 · 3.26 Impact Factor
  • María del Carmen Contini · Alejandro Ferri · Claudio A Bernal · Cristina E Carnovale
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    ABSTRACT: Effects of both chronic aluminum (Al) exposure and partial hepatectomy on iron (Fe) homeostasis were studied. Male Wistar rats were intraperitoneally administered either 27 mg Al/kg body weight (as aluminum hydroxide) or the vehicle saline, three times a week for 3 mo. After this time, half of the rats of each group was sham operated (SH) and the other half was partially hepatectomized (PH). Animals of the four experimental groups (vehicle+SH [SH]; Al+SH; vehicle+PH [PH], and Al+PH) were killed 48 h after the surgical procedure. Serum, hepatic, and intestinal Al levels were found to be increased both for Al+SH and Al+PH. The serum Fe concentration and transferrin saturation percentage were significantly diminished in the rats of the Al+PH group, thus showing interaction between Al administration and PH. The 59Fe mucosal-to-serosal transport, studied in the intestinal loop in situ, was not affected by Al or PH. The malregulation of intestinal Fe absorption in Al exposure and/or PH when the serum Fe concentration was diminished could be the result of the increased lipid peroxidation (thiobarbituric acid-reactive substances [TBARS]) observed in this tissue. Mucosal TBARS were increased by Al exposure (+26%) and PH (+37%) and interaction between Al and PH was observed (+44%). These results show that when liver surgery is performed after prolonged Al exposure, it leads to impairment of Fe homeostasis. We underline the importance of the exposure to Al, a potentially toxic element, in the study of risk assessment in patients who must be submitted to major liver resection.
    Biological Trace Element Research 02/2007; 115(1):31-45. DOI:10.1385/BTER:115:1:31 · 1.75 Impact Factor
  • 12/2006; 10(1). DOI:10.14409/fabicib.v10i1.799
  • M. del C Contini · C. Bernal · M. González · S. Mahieu · C. Carnovale
    12/2006; 10(1). DOI:10.14409/fabicib.v10i1.786
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    ABSTRACT: The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis.
    Toxicology 07/2006; 223(3):209-18. DOI:10.1016/j.tox.2006.03.018 · 3.62 Impact Factor
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    ABSTRACT: The aim of our work was to analyze the hemorheological parameters following partial hepatectomy in rats with chronic Al-intoxication (Al). Male Wistar rats were randomly assigned into four experimental groups (n=6 each one): Sham (rats subjected to simulated surgery); Al+Sham; Partial Hepatectomy (animals subjected to 65% liver resection) and Al+Partial Hepatectomy. Our results show that both Partial Hepatectomy and Al treatment produce a decrease of plasma cholesterol level, which showed a negative association with Rigidity Index increase (r(s)=-0.6475, p<0.05). The increase of Rigidity Index observed in Partial Hepatectomy, Al+Sham and Al+Partial Hepatectomy could be related to the increase of the proportion of non-discocytic erythrocytes, particularly stomatocytes, which determines a diminution of the Morphological Index. In the Altreated groups, greater changes in Rigidity Index and Morphological Index were observed. The relative viscosity of blood at a standard haematocrit of 40% was increased in Partial Hepatectomy, Al+Sham and Al+Partial Hepatectomy as compared to Sham, due to erythrocyte rigidity. On the other hand, we observed that the increase of plasma fibrinogen concentration correlates with augmentation of plasma viscosity (r(s)=0.689, p=0.004) for all the experimental groups studied. The results indicate that both administration of Al and Partial Hepatectomy induce microcytic hypocromic anaemia in the rats reflected by a significant decrease of haematocrit, mean corpuscular volume and mean corpuscular haemoglobin concentration. From these results, we conclude that in partially hepatectomized, Al-overloaded rats the decrease in erythrocyte deformability may be an important factor leading to the installation of anaemia.
    Clinical hemorheology and microcirculation 01/2006; 35(4):431-9. · 2.24 Impact Factor
  • Stella Mahieu · Néstor Millen · María del Carmen Contini · Marcela Manuale
    12/2005; 1(5). DOI:10.14409/au.v1i5.991
  • 12/2005; 9(1). DOI:10.14409/fabicib.v9i1.773
  • 12/2005; 8(1). DOI:10.14409/fabicib.v8i1.743
  • M. C. Contini · M. González · S. Mahieu · C. Carnovale · C. Bernal
    12/2005; 8(1). DOI:10.14409/fabicib.v8i1.734
  • Marcela González · María del Carmen Contini · Néstor Millen · Stella Mahieu
    12/2005; 2(1). DOI:10.14409/fabicib.v2i1.600
  • Stella Mahieu · María Luisa Calvo · Nestor Millen · María del Carmen Contini · Marcela González
    12/2005; 2(1). DOI:10.14409/fabicib.v2i1.608
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    ABSTRACT: Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys.
    Journal of Inorganic Biochemistry 10/2005; 99(9):1858-64. DOI:10.1016/j.jinorgbio.2005.06.023 · 3.44 Impact Factor
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    ABSTRACT: Aluminium (Al (III)) is a metal with no biological function. Its organic accumulation can lead to toxic effects. To elucidate the in vivo effect of Al (III) upon the rheological properties of the erythrocyte membrane, male adult Wistar rats have been submitted to periodical injections of Al(OH)3 during three months. Significant decreases in haematocrit (34+/-0.37% versus 36+/-0.20%, p<0.0001) and blood haemoglobin concentration (10.7+/-0.15 g/dl versus 12.3+/-0.49 g/dl, p<0.005) have been found. Haemolysis curves shifted towards the left, indicating that erythrocytes became more resistant to hypotonic haemolysis. Significant increments in rigidity index (29.6+/-1.59 versus 9.2+/-0.40, p<0.0001), relative viscosity at native haematocrit (3.6+/-0.03 versus 3.5+/-0.03, p<0.04), and relative viscosity at standard haematocrit (4.5+/-0.06 versus 3.9+/-0.05, p<0.0001) have been observed. The decrease in the erythrocyte aggregate size (1.6+/-0.01 versus 1.7+/-0.01, p<0.002) and the aggregation rate (0.5+/-0.02 versus 0.6+/-0.03, p<0.002) indicated a significantly dropped aggregability process. In conclusion, Al (III) disorganised the erythrocyte membrane by altering its mechanical properties, suggesting a reduction of the middle life of circulating erythrocytes, which could play a major role in the anaemia of these animals.
    Journal of Inorganic Biochemistry 04/2005; 99(3):822-7. DOI:10.1016/j.jinorgbio.2004.12.012 · 3.44 Impact Factor
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    ABSTRACT: The effect of chronic aluminum (Al) administration on the phosphorous (Pi) metabolism of different target tissues was studied. Male Wistar rats received aluminum lactate for 3 months (5.75 mg/kg bodyweight of Al, i.p., three times per week). The animals were studied at the end of the 1st, 2nd and 3rd month of treatment. They were housed individually in metabolic cages for 4 days to study Pi and calcium (Ca) balance. Daily food and water intakes were recorded for all animals and urine and feces were collected for Pi and calcium assays. After 3 months the Pi intestinal absorption and the Pi deposition in bone were studied using 32Pi. Another group of rats was treated daily for 7 days with calcitriol (0.08 microg/kg body weight in sesame oil, i.p.) and the Pi balance was studied for the last 4 days. The results indicated that chronic administration of Al affected simultaneously the Pi and calcium balance, with a significant diminution of calcium and increased Pi accretion in bones, together with a diminution in the intestinal absorption of Pi. The treatment of the rats with calcitriol promoted a normalized Pi balance in Al treated rats. These findings suggest that Al could modify the Pi metabolism acting directly on intestine, kidney and bone, or indirectly through possible changes in the levels of vitamin D3.
    Archive für Toxikologie 12/2004; 78(11):609-16. DOI:10.1007/s00204-004-0579-7 · 5.98 Impact Factor
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    Stella Mahieu · Maria del Carmen Contini · Marcela Gonzalez · Nestor Millen · Maria Monica Elias
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    ABSTRACT: Sequential effects of intoxication with aluminum hydroxide (Al) (80 mg/Kg body weight, i.p., three times a week), were studied on rats from weaning and up to 28 weeks. The study was carried out on hematological and iron metabolism-related parameters on peripheral blood, at the end of the 1st, 2nd, 3rd, 4th, 5th and 6th months of exposure. As it was described that hematotoxic effects of Al are mainly seen together with high levels of uremia, renal function was measured at the same periods. The animals treated developed a microcytosis and was accompanied by a decrease in mean corpuscular hemoglobin (MCH). Significantly lower red blood cell counts (RBC million/microl) were found in rats treated during the 1st month. These values matched those obtained for control rats during the 2nd month. From the 3rd month onwards, a significant increase was observed as compared to control groups, and the following values were obtained by the 6th month: (T) 10.0 +/- 0.3 versus (C) 8.7 +/- 0.2 (million/microl). Both MCH and mean corpuscular volume (MCV) were found to be significantly lower in groups treated from the 2nd month. At the end of the 6th month the following values were found: MCH (T) 13.3 +/- 0.1 versus (C) 16.9 +/- 0.3 (pg); MCV (T) 42.1 +/- 0.7 versus (C) 51.8 +/- 0.9 (fl). Al was found responsible for lower serum iron concentration levels and in the percentage of transferrin saturation. Thus, although microcytic anemia constitutes an evidence of chronic aluminum exposure, prolonged exposure could lead to a recovery of hematocrit and hemoglobin concentration values with an increase in red cell number. Nevertheless, both microcytosis and the decrease of MCH would persist. These modifications took place without changes being observed in the renal function during the observation period.
    Toxicology Letters 02/2000; 111(3):235-42. DOI:10.1016/S0378-4274(99)00184-8 · 3.26 Impact Factor
  • S Mahieu · M L Calvo · N Millen · M Gonzalez · M C Contini
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    ABSTRACT: The effects of aluminum on growth have been studied in rats chronically poisoned with aluminum hydroxide (80 mg/kg b.w.-i.p.-three times a week, during 6 months) and in control rats, between 3 and 26 weeks of age. The growth data was evaluated according to Parks 'theory of feeding an growth. At the end of the poisoning period, the calcium metabolism was studied through a balance of calcium and the determination of bone Ca++ accretion and resorption rates with the aid of 45Ca++. The parathyroid glands function was studied using an indirect method. Treated rats showed a significant decrease in asymptotic weights and in the initial efficiency of food conversion into biomass regarding controls. No differences were observed in food intake between both group. Aluminum affected neither the peak growth rate nor the time necessary to attain maturity. The calcium balance in treated rats was significantly less than in the control group. This was accompanied by a significant increase in the calcium excreted by faces, caused perhaps by a less intestinal absorption. An important amount of aluminum on the surface of the trabecular bone and a reduction in the skeletal Ca++ mass, was observed in all treated rats. Nevertheless there are no differences in the latter when expressed for 100 g of body weight. The rate of skeletal Ca++ accretion was found to be significantly decreased in treated group with respect to controls, without any changes in the bone Ca resorption rate. The reduction in bone turnover revealed by the decrease of Vo+/Vo- was accompanied by less recovery velocity of calcemia in the aluminum treated group, being indirectly related to the parathyroid gland response to calcium depletion. In the model that we studied the decreased bone turnover could have been caused by deposits of aluminum in bone; however there could exist associated factors such as dysfunction in the secretion of PTH, or less affinity between its receptors at the bone level.
    Acta physiologica, pharmacologica et therapeutica latinoamericana: órgano de la Asociación Latinoamericana de Ciencias Fisiológicas y [de] la Asociación Latinoamericana de Farmacología 01/1998; 48(1):32-40.

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