The Role of Glycogen Synthase Kinase-3ß in the Zinc-Mediated Neuroprotective Effect of Metformin in Rats with Glutamate Neurotoxicity.

Metformin has been suggested to have protective effects on the central nervous system, but the mechanism is unknown. The similarity between the effects of metformin and the inhibition of glycogen synthase kinase (GSK)-3ß suggests that metformin may inhibit GSK-3ß. In addition, zinc is an important element that inhibits GSK-3ß by phosphorylation. In this study, we investigated whether the effects of metformin on neuroprotection and neuronal survival were mediated by zinc-dependent inhibition of GSK-3ß in rats with glutamate-induced neurotoxicity. Forty adult male rats were divided into 5 groups: control, glutamate, metformin + glutamate, zinc deficiency + glutamate, and zinc deficiency + metformin + glutamate. Zinc deficiency was induced with a zinc-poor pellet. Metformin was orally administered for 35 days. D-glutamic acid was intraperitoneally administered on the 35th day. On the 38th day, neurodegeneration was examined histopathologically, and the effects on neuronal protection and survival were evaluated via intracellular S-100ß immunohistochemical staining. The findings were examined in relation to nonphosphorylated (active) GSK-3ß levels and oxidative stress parameters in brain tissue and blood. Neurodegeneration was increased (p < 0.05) in rats fed a zinc-deficient diet. Active GSK-3ß levels were increased in groups with neurodegeneration (p < 0.01). Decreased neurodegeneration, increased neuronal survival (p < 0.01), decreased active GSK-3ß (p < 0.01) levels and oxidative stress parameters, and increased antioxidant parameters were observed in groups treated with metformin (p < 0.01). Metformin had fewer protective effects on rats fed a zinc-deficient diet. Metformin may exert neuroprotective effects and increase S-100ß-mediated neuronal survival by zinc-dependent inhibition of GSK-3ß during glutamate neurotoxicity.

Trace Element Status and Postoperative Morbidity After On-pump Coronary Artery Bypass Surgery.

Trace elements are essential micronutrients that take part in most antioxidant reactions in the body. In this study, we evaluated the levels of copper, chromium, manganese, selenium, magnesium, zinc, iron, and silicon in adult patients who undergone isolated on-pump coronary artery bypass with the occurrence of postoperative atrial fibrillation, transient renal injury, transient liver injury, and rate of wound infection; 51 adult patients (41 men, 10 women) underwent isolated coronary artery bypass grafting (CABG) under cardiopulmonary bypass. The mean age was 61,9 ± 8,0 years (range 45-82 years). Blood samples were collected preoperatively, postoperative first hour, postoperative first day, and fifth postoperative day for element analysis. Serum levels were determined by an Inductive Coupled Plasma Optical Emission Spectrometer (ICAP 6000). Serum copper, zinc, and selenium values, typically known as strong antioxidant elements in the body, decreased significantly during the first hour and first day of postoperative period compared to the preoperative period (p < 0.05). Also, postoperative atrial fibrillation, transient renal injury, transient liver injury, and rate of wound infection were observed to increase with the decrease in levels of trace elements (p < 0.05). The levels of these elements were observed to return to normal levels during the fifth postoperative day. The levels of trace elements decrease significantly after on-pump coronary artery bypass surgery. Our study results suggest that this could be one of the predisposing factors for increased postoperative atrial fibrillation, transient kidney injury, transient renal injury, and increased rate of wound infections for patients undergoing on-pump coronary artery bypass grafting.

Comparison of trace element levels after cardiopulmonary bypass between cyanotic and acyanotic patients.

Trace elements are essential micronutrients for the human body. In this study, we evaluated the alterations in copper, chromium, manganese, selenium, magnesium, zinc, iron, arsenic, boron, and silicon levels in children with cyanotic and acyanotic CHD who underwent cardiac surgery with cardiopulmonary bypass. Participants were divided into the following three groups: patients acyanotic CHDs (n=34), patients with cyanotic CHDs (n=30), and healthy controls (n=30). Blood samples were collected before the surgery and 1 hour after the sternum was closed. Serum trace elements were determined by Inductively Coupled Plasma Optical Emission Spectrometer-ICAP 6000. The baseline serum arsenic, manganese, and zinc levels of both patient groups were lower compared with controls, but there was no significant difference between baseline serum trace element levels of cyanotic and acyanotic patients. In both the patient groups, there was a significant decrease in postoperative serum arsenic, boron, copper, and zinc levels, and a significant increase in postoperative serum iron and magnesium levels. Silicon levels increased in cyanotic patients. Alterations in trace element levels were in the same direction in cyanotic and acyanotic patients. Copper, zinc, and manganase replacement may be needed after on-pump cardiac surgery.