Relationship between serum lithium concentration and kidney damage in a preclinical model

Objectives: The aim of the present study was to assess whether there is a relationship between serum lithium concentrations and the magnitude of kidney damage in a preclinical model. Methods: Thirty Wistar male rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months; and experimental groups fed ad libitum the same diet supplemented with 30 or 60 mmol/kg diet for 3 months (LowLi and HighLi groups respectively). Laboratory parameters were assessed at months 1 and 3 and histopathological changes were evaluated after 3 months. Results: Serum lithium levels in experimental rats were within therapeutic range used in humans throughout the entire experiment. After 3 months of treatment, lithium levels were statistically higher in HighLi group. Rats of the LowLi group showed dilation of cortical tubules although with similar clearance of creatinine. Rats from the HighLi group had greater histopathological damage in addition to lower creatinine clearance than the other two groups. Conclusions: Our study suggests that during long-term treatments, even with serum lithium levels within the therapeutic range used in humans, the risk of kidney damage could increase proportionally to the serum lithium concentration.Fil: Ossani, Georgina Paula. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; ArgentinaFil: Uceda, Ana Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Variable Number Tandem Repeats in the promoter region of prostacyclin synthase gene in choline deficient rats.

Weanling Sprague-Dawley rats were fed on a choline-deficient diet with hydrogenated vegetable oil and corn oil as lipids develop acute renal failure. Pathogenesis of the latter is controversial and an ischemic mechanism has been proposed. Arachidonic acid derivatives are involved in the regulation of vascular tonus. Vasospasm could be due to an increase in tromboxane A2-mediated vasoconstriction or to a decrease in prostacyclin-induced vasodilatation. Enzymes involved in the synthesis of both compounds are tromboxane A2- and prostacyclin-synthase respectively. The aim of this study was to identify the variable number tandem repeats (VNTR) in the promoter region of prostacyclin synthase gene and verify if there exists a relationship between the occurrence of VNTR in those choline-deficient rats which die because of acute renal failure and those which do not. We verified the presence of the VNTR in the prostacyclin synthase rat gene, but we did not find any difference in the molecular weight of the alleles between experimental and control rats. Renal reparation of the acute kidney injury due to choline deficiency in some rats is not related with differences in VNTR in the promoter region of the prostacyclin synthase gene. Weanling Sprague-Dawley rats fed a choline-deficient diet with hydrogenated vegetable oil and corn oil as lipids develop acute renal failure. Its pathogenesis is controversial. The ischemic mechanism has been proposed. Derivatives from arachidonic acid are involved in the regulation of vascular tone. Vasospasm could be due to an increase in vasoconstriction mediated by tromboxane A2 or a decrease in vasodilatation by prostacyclin. Enzymes involved in the synthesis of them are tromboxane A2 and prostacyclin synthase respectively. The aim of this study is to identify the variable number tandem repeats (VNTR) in the promoter region of prostacyclin synthase gene and verify if there exists a relationship between the VNTR and those rats which dye as a consequence of acute renal failure due to choline deficiency and those which do not die. The VNTR presence was detected by molecular methods. We verified the presence of the VNTR in the prostacyclin synthase rat gene. We did not find difference in the molecular weight of the alleles between experimental and control rats. Renal reparation of the acute kidney injury due to choline deficiency in Sprague-Dawley rats is not related with differences in prostacyclin synthase VNTR, in the promoter region of this gene.Fil: Denninghoff, Valeria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ossani, Georgina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Uceda, Ana Margarita. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Avagnina Iribarren, Maria Alejandra. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Elsner, Boris. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Monserrat, Alberto Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentin

Adelante / Endavant

Séptimo desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere "Purificación Escribano" de la Universitat Jaume

Relationship between serum lithium concentration and kidney damage in a preclinical model

Objectives: The aim of the present study was to assess whether there is a relationship between serum lithium concentrations and the magnitude of kidney damage in a preclinical model. Methods: Thirty Wistar male rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months; and experimental groups fed ad libitum the same diet supplemented with 30 or 60 mmol/kg diet for 3 months (LowLi and HighLi groups respectively). Laboratory parameters were assessed at months 1 and 3 and histopathological changes were evaluated after 3 months. Results: Serum lithium levels in experimental rats were within therapeutic range used in humans throughout the entire experiment. After 3 months of treatment, lithium levels were statistically higher in HighLi group. Rats of the LowLi group showed dilation of cortical tubules although with similar clearance of creatinine. Rats from the HighLi group had greater histopathological damage in addition to lower creatinine clearance than the other two groups. Conclusions: Our study suggests that during long-term treatments, even with serum lithium levels within the therapeutic range used in humans, the risk of kidney damage could increase proportionally to the serum lithium concentration.Fil: Ossani, Georgina Paula. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; ArgentinaFil: Uceda, Ana Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Renal Damage During Continuous Versus Intermittent Treatment with Lithium

The aim of this study was to evaluate renal damage in animals treated with lithium continuously versus intermittently. Rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months and two experimental groups, one of them fed ad libitum the same diet or the same diet supplemented with 60 mmol of lithium/kg diet every alternate week, for 3 months and the other fed ad libitum powered standard diet for one and a half month and the same diet supplemented with 60 mmol of lithium/kg diet for the last month and a half. Lithemias in experimental groups were within therapeutic range used in humans. At the end of the protocol, diuresis was higher in experimental groups compared to control group. There was no difference in serum creatinine and creatinine clearance. Both experimental groups showed hypertrophy, hyperplasia, and dilatation of cortical collecting tubules although dilatation was greater in continuous group. Longer studies are necessary to clarify the evolution of renal damage. Our preliminary study shows that histopathological damage associated with the use of lithium occurs during both continuous and intermittent treatment, but it seems to be somewhat greater in the continuous group.Fil: Ossani, Georgina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Uceda, Ana Margarita. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Ponzo, Osvaldo Juan. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Nitric oxide and AQP2 in hypothyroid rats: A link between aging and water homeostasis

Objective Hypothyroid state and aging are associated with impairment in water reabsorption and changes in aquaporin water channel type 2 (AQP2). Nitric oxide (NO) is involved in AQP2 trafficking to the apical plasma membrane in medullary collecting duct cells. The purpose of this study was to investigate whether aging and hypothyroidism alter renal function, and whether medullary NO and AQP2 are implicated in maintaining water homeostasis. Materials/Methods Sprague-Dawley rats aged 2 and 18 months old were treated with 0.02% methimazole (w/v) during 28 days. Renal function was examined and NO synthase (NOS) activity ([14C (U)]-L-arginine to [14C (U)]-L-citrulline assays), NOS, caveolin-1 and -3 and AQP2 protein levels were determined in medullary tissue (Western blot). Plasma membrane fraction and intracellular vesicle fraction of AQP2 were evaluated by Western blot and immunohistochemistry. Results A divergent response was observed in hypothyroid rats: while young rats exhibited polyuria with decreased medullary NOS activity, adult rats exhibited a decrease in urine output with increased NOS activity. AQP2 was increased with hypothyroidism, but while young rats exhibited increased AQP2 in plasma membrane, adult rats did so in the cytosolic site. Conclusions Hypothyroidism contributes in a differential way to aging-induced changes in renal function, and medullary NO and AQP2 would be implicated in maintaining water homeostasis.Fil: Sarati, Lorena Ivonne. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Aleman. Laboratorio de Medicina Experimental; ArgentinaFil: Martinez, Carla Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Uceda, Ana Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Aleman. Laboratorio de Medicina Experimental; ArgentinaFil: Feldman, Mariana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Aleman. Laboratorio de Medicina Experimental; ArgentinaFil: Balaszczuk, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Fellet, Andrea L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

Menhaden oil rich diet and experimental renal damage due to ischemia reperfusion

Renal necrosis can be induced in weanling rats due to choline deficient diet. Menhaden oil has a protective effect against the development of renal necrosis in choline deficient weanling rats. The aim of this work was to determine the effects of menhaden oil in a model of acute kidney injury due to ischemia reperfusion. Wistar rats were divided into two groups and fed vegetable oils or menhaden oil as lipids. Unilateral renal ischemia was performed for 30 minutes and animals were sacrificed 48 hours later. Histopathological examination showed no significant differences between groups. Menhaden oil did not prevent histopathological lesions.Fil: Ossani, Georgina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Marcotegui, Ariel R.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Uceda, Ana Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Monserrat, Alberto Juan. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Lago, Néstor Rubén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Perazzo, Juan C.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentin

Short-term Menhaden Oil Rich Diet Changes Renal Lipid Profile in Acute Kidney Injury

Weanling male Wistar rats fed a choline-deficient diet develop acute kidney injury. Menhaden oil, which is a very important source of omega-3 fatty acids, has a notorious protective effect. The mechanism of this protection is unknown; one possibility could be that menhaden oil changes renal lipid profile, with an impact on the functions of biological membranes. The aim of this work was to study the renal lipid profile in rats fed a choline-deficient diet with menhaden oil or vegetable oil as lipids. Rats were divided into 4 groups and fed four different diets for 7 days: choline-deficient or choline-supplemented diets with corn and hydrogenated oils or menhaden oil. Serum homocysteine, vitamin B12, and folic acid were analyzed. Renal lipid profile, as well as the fatty acid composition of the three oils, was measured. Choline-deficient rats fed vegetable oils showed renal cortical necrosis. Renal omega-6 fatty acids were higher in rats fed a choline-deficient diet and a choline-supplemented diet with vegetable oils, while renal omega-3 fatty acids were higher in rats fed a choline-deficient diet and a choline-supplemented diet with menhaden oil. Rats fed menhaden oil diets had higher levels of renal eicosapentaenoic and docosahexaenoic acids. Renal myristic acid was increased in rats fed menhaden oil. The lipid renal profile varied quickly according to the type of oil contented in the diet.Fil: Ossani, Georgina Paula. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Denninghoff, Valeria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: Uceda, Ana Margarita. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; ArgentinaFil: Díaz, Maria L.. Hospital Británico de Buenos Aires; ArgentinaFil: Uicich, Raúl. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Monserrat, Alberto Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología. Centro de Patología Experimental; Argentin

Role of Oxidative Stress in Lithium-Induced Nephropathy

Long-term lithium treatment was associated with chronic kidney disease and renal failure although the underlying pathogenic mechanisms are not certainty known. The aim of this study was to evaluate changes in oxidative stress measures as well as renal functional and structural alterations associated with chronic use of lithium in rats. Forty Wistar male rats were randomized into four groups: control groups fed ad libitum powered standard diet for 1 and 3 months and experimental groups fed ad libitum the same diet supplemented with 60 mmol/kg diet for 1 and 3 months. Histopathological changes, laboratory parameters, and oxidative stress measurements were assessed at months 1 and 3. The experimental animals showed alteration of the cortical tubules from the first month of lithium-treatment and a decrease in the glomerular filtration rate and in the glomerular area at the third month. There was an increase in thiobarbituric acid reactive substances and carbonyls, as well as an increase in reduced glutathione, in the kidney of rats exposed to lithium. These changes were evident from the first month of treatment and remained throughout the experiment. Our results suggest that, oxidative stress could be one of the pathogenic mechanisms involved in the structural and functional alterations of the kidney associated with prolonged use of lithium. The study of the pathogenic mechanisms involved in lithium-induced nephropathy is a critical issue for the development of new strategies for prevention and/or early detection.Fil: Ossani, Georgina Paula. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Uceda, Ana Margarita. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Acosta, Juan M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Lago, Néstor Rubén. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Patología; ArgentinaFil: Repetto, Marisa Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; ArgentinaFil: Toblli, Jorge Eduardo. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin