Antioxidant defense system maintains the viability in Langerhans islets after a chronic cadmium exposure in Wistar rats

Antioxidant defense system maintains the viability in Langerhans islets after a chronic cadmium exposure in Wistar rats

S162 Abstracts / Toxicology Letters 259S (2016) S73–S247 by the ATSDR. Previous studies have linked cadmium exposure to disturbances in carbohydrate...

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S162

Abstracts / Toxicology Letters 259S (2016) S73–S247

by the ATSDR. Previous studies have linked cadmium exposure to disturbances in carbohydrate and lipid metabolism. Objective: Study the effect of an oral cadmium administration in drinking water in rats, on the Chron carbohydrates and lipids, and the insulin resistance. Materials and methods: Wistar rats were exposed to CdCl2 in drinking water, “ad libitum”, (32.5 ppm, LOAEL dosage) by 2, 3 and 4 months. Just before to the end the exposure, rats received an oral glucose load equivalent to 1.75 g-glucose/kg. Rats were anesthetized, and whole blood (200 ␮L) was obtained by cardiac puncture at 0, 30, 60 and 90 min, then glucose and insulin in serum were measured. Also were measured, cholesterol and its fractions (VLDL, LDL and HDL), triglycerides and FFA levels. The effect of Cd on insulin resistance/sensitivity in liver, muscle, adipose and cardiovascular tissue were studied, by means of mathematical models. Results: Cd exposure to rats induces hyperglycemia and hyperinsulinemia after a glucose load. Produce the increase in serum of FFA, TG, Chol, LDL and VLDL lipoproteins, and a decrease of HDL fraction. After exposure, a decrease of insulin sensitivity was shown in muscle and liver. Additionally, Cd increases insulin resistance in the liver, adipose tissue and cardiovascular system. Finally, ␤-cell functioning which was evaluated by HOMA-B% index and insulin disposition index, showed decreases, while insulin generation index increased Conclusions: Cadmium administration to rats, increases insulin release, induces the development of a hyperglycemia, and alters lipid metabolism. These changes likely occur as a consequence of reduced sensitivity and increased insulin resistance in insulin-dependent tissues and non-dependent tissues, producing a biochemical phenotype similar to metabolic syndrome and diabetes. Financial support: Authors thank CONACYT by this work was supported and VIEP-BUAP projects. http://dx.doi.org/10.1016/j.toxlet.2016.07.384 PP16.9 Antioxidant defense system maintains the viability in Langerhans islets after a chronic cadmium exposure in Wistar rats ˜ 1 , A. Diaz 3 , P. Aguilar-Alonso 1 , J.A. Flores-Hernández 2 , S. Trevino E. Brambila 1 1

Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, BUAP, Mexico 2 Departamento de Análisis Clínicos, Facultad de Ciencias Químicas, BUAP, Mexico 3 Departamento de Farmacia, Facultad de Ciencias Químicas, BUAP, Mexico Introduction: Previously we found that rats exposed chronically to cadmium (Cd) present hyperinsulinemia and hyperglycemia. It is well known that oxidative stress produced by Cd is involved with the toxicity of a number tissues, however, few studies have been conducted to determine if a LOAEL dose of Cd exposure produces the accumulation of Cd in Langerhans islets, oxidative stress, and the response of this tissue to these changes. This information can give a clue to explain the observed hyperinsulinemias in rats exposed to Cd. Objective: Study the redox balance and viability of the Langerhans islets of rats chronically exposed with cadmium in drinking water. Materials and methods: Groups of Wistar rats were exposed to CdCl2 (32.5 ppm) in drinking water, “ad libitum”, during 2, 3 and 4 months. After each point time, the rats were anesthetized, and a

pancreatectomy was realized. Samples of pancreas were used for Cd quantification, balance redox and histological valuation with orange acridine staining. Results: After 2, 3 and 4-months of Cd-exposure, the metal was accumulated in pancreatic tissue. Also, pancreas of rats shown an increase of lipoperoxidation and Reactive Oxigen Species, without change in nitric oxide level. GSH and metallothionein (MT) were increased, as well as activities of SOD, CAT and GST. GPx show a dual activity with activity increased 2-months after Cd exposure, and activity depleted at end of the study; GR activity also diminished after 4-months Cd-exposition. The multi-chaperone complex (HSF-1, HSP70 and HSP90) was increased. Finally, cells in Langerhans islets showed a high cellular viability, without evidence of apoptosis and necrosis. Conclusions: Cd accumulation in Langerhans islets induces an oxidative environment, however, the enzymatic and nonenzymatic defense antioxidant systems are able of maintain the viability cell, at expense of hyperinsulinemic states which could cause ␤-cell exhaustion and diabetogenic development. Financial support: Authors thank CONACYT by this work was supported and VIEP-BUAP projects. http://dx.doi.org/10.1016/j.toxlet.2016.07.385 PP16.10 Changes on hepatic lipidome and HDL-lipoproteins phenotype of Wistar rats exposed chronically to cadmium V.E. Sarmiento-Ortega 1 , E. Brambila 1 , J.A. Flores-Hernández 2 , P. ˜ 1 Aguilar-Alonso 1 , D. Moroni 1 , A. Diaz 3 , S. Trevino 1

Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, BUAP, Mexico 2 Departamento de Análisis Clínicos, Facultad de Ciencias Químicas, BUAP, Mexico 3 Departamento de Farmacia, Facultad de Ciencias Químicas, BUAP, Mexico Introduction: Cadmium (Cd) exposure is associated with an important number of toxic effects in animals and humans. Recently, Cd has been linked with metabolic disorders, including dyslipidemia. Previous reports have shown that Cd accumulation in liver generates lipoprotein abnormalities. Objective: Investigate the effect of a Cd oral exposition on the changes of lipidome in liver and serum of Wistar rats. Material and methods: Groups of Wistar rats were exposed “ad libitum” with CdCl2 (32.5 ppm) in drinking water for 3, 4 and 5 months. After each time exposure, the blood and liver of each animal were obtained and stored. In liver, Cd accumulation was evaluated by AAS. Meanwhile, the content of lipids was measured with spectrophotometric assays. In serum, the complete lipid profile was measured with commercial kits. In addition, sub-fractions of lipoproteins were separated by polyacrylamide gel electrophoresis and later evaluated. Results: After Cd-administration, liver showed an accumulation time-dependent, and the amount of triglycerides, cholesterol and phospholipids increased significantly. In serum, rats exposed showed dyslipidemia, which was characterized by the increase of triglycerides, free fatty acids and the lipoprotein fractions (VLDL and LDL), but a significant reduction in HDL. Analysis of the lipoprotein sub-fractions, also showed alterations in VLDL1, an atherogenic phenotype of LDL IIIa, IIIb, IVa and IVb, and changes in HDL 3b and 3c. The evaluation of the HDL-lipidome was characterized by the increased of triglycerides and phospholipids, but with a decrease of esterified and non-esterified cholesterol.