Hematological and cardiac effects of excess zinc in rats

In this work administration of zinc sulphate at a dose of 20 mg/kg/day. 6 days/week for 4 successive weeks, resulted in significant decrease in RBCs count, hemoglobin content, hematocrit value and mean corpuscular hemoglobin concentration in zinc treated group compared to control group. Biochemical studies showed significant decrease in plasma triglyceride, and malondialdehyde levels in zinc treated group compared to control group. However, non significant difference was found between the two groups as regards plasma zinc level. ECG study demonstrated significant increase in heart rate [HR] in zinc treated group compared to control group. This was accompanied by shortening of QRS and prolongation in Q-Tc durations in zinc treated group compared to control group. In vitro study of isolated hearts perfused in a Langendorff preparation, significant increase in basal HR was shown in zinc treated group compared to control group. The maximal HR upon isoproterenol infusion [ISU], when expressed as percentage ratio from baseline values, showed significant decrease in zinc treated group compared to control group. As regards baseline peak tension [PT] and peak tension/left ventricular weight [PT/LV,], significant increase was found in zinc treated group compared to control group. Also, the PT maximal response upon ISU infusion, either absolute or upon correction of left ventricular weight, showed significant increase in zinc treated group. Significant shortening in baseline time to peak tension [TPT] and half relaxation time [l/2RT,] were noticed in zinc treated group compared to control group. However, basal myocardial flow rate [MFR] as well as MFR/L V showed non significant difference between the 2 studied groups. Post ischemic reperfusion responses showed non significant difference as regards HR between the 2 studied groups. The recovery of PT and PT/LV were significantly higher at 20, 25, and 30 minutes of reperfusion in zinc treated group compared to control group. As regard TPT reperfusion values, significant prolongation at 10 minute was noticed in zinc treated group compared to control group. However 1/2RT, MFR and MFR/LV reperfusion values, non significant differences were recorded between the two studied groups. From this study, it can be concluded that zinc administration at a dose of 20 mg/kg/day for 4 successive weeks, has a protective effect against the risk of atherosclerosis and oxidative stress in vivo. Also, zinc treatment maintained or even enhanced the intrinsic cardiac functions, both chronotropic and inotropic, and their responses to B-adrenergic stimulation. In addition, zinc proved to be a beneficial cardioprotective agent as it attenuated the detrimental effects of post-ischemia reperfusion on the myocardial contractility

Differential effects of vitamin E supplementation on cardiovascular risk factors and on cardiac vulnerability to ischemia and reperfusion in rats

The present study was performed to examine the effects of vitamin E on hemodynamics, electrocardiogram [ECG] pattern, plasma levels of lipid profile, enzymes reflecting myocardial cell integrity creatine kinase [CK] and lactate dehydrogenase [LDH] and rate of lipid peroxidation as well as on myocardial performance after ischemia-reperfusion injury in isolated rat hearts. Vitamin E-treated rats were injected with vitamin E in a dose of 4 mg/100g body weight [b.w.] daily, for 6 consecutive days. Control rats were treated with vitamin E-solvent, daily, for the same duration. Then, rats were sacrificed, and the isolated heart were subjected to 30 min. ischemia followed by 30 min period of reperfusion. The present study demonstrated that administration of vitamin E in normal rats did not produce any appreciable hemodynamic effects as regards heart rate [HR], mean arterial pressure [MAP,], and pressure rate product[PRP]. The ECG pattern showed no arrhythmias or ischemic changes compared to control group. Concerning changes in plasma lipid profile, vitamin E-treated rats showed significant reduction in both total cholesterol [TC], and low density lipoprotein-cholesterol [LDL-C] Moreover, high density lipoprotein-cholesterol / total cholesterol [HDL-C/TC] was significantly elevated, in contrast to a non significant decrease in both low density lipoprotein-cholesterol/ total cholesterol [LDL-C /TC] and LDL-C /HDL-C ratios, when compared with controls. Myocardial cellular integrity, estimated by the plasma level of CK and LDH, was preserved by the administration of vitamin E, revealed evidently by the significant decrease in CK and LDH release in plasma of rats treated with vitamin E as compared to control rats. Moreover, the plasma level of malondialdehyde, as an index for the degree of lipid peroxidation, was significantly reduced. The preischemic, baseline activity of the isolated hearts obtained from rats treated with vitamin E, revealed non significant changes in myocardial inotropy except for prolongation of half relaxation time. Also there was a significant reduction in both heart rate and LDH release in the coronary effluent, while there was a non significant change in tile coronary flow rate. The results of the isolated hearts subjected to reperfusion following 30 minutes ischemic period, showed that vitamin E decreased the detrimental effect of reperfusion on the inotropic activity observed in the control group, evident by superior recovery of postischemic reperfusion myocardial functions. Manifested by elevated peak developed tension, and tension generation per unit time, concomitant with shortening of time to peak tension, and half relaxation time, along the reperfusion period. In addition, the percentage recovery of the heart rate was better during the whole reperfusion period but the difference was statistically significant only at 15-minute of reperfusion, and as well myocardial flow rate percentage .showed significant superior recovery in vitamin E-treated rat hearts. Moreover, there was a significant reduction in both CK and LDH release in the coronary effluent of vitamin E treated rat hearts, compared to control hearts. It could be concluded that vitamin E administration has a favorable potential against the risk of atherosclerosis and lipid peroxidation and as well it may attenuate the detrimental effects of postischemic reperfusion on the myocardial contractility

In vitro effects of trace elements on blood clotting and platelet function [B-zinc and magnesium]

The in vitro effects of zinc and magnesium salts on blood coagulation mechanism and platelet aggregation were studied on rat plasma. Addition of zinc sulphate to pooled rat plasma in a range of concentrations [0.3-1 mg/ml] caused a dose dependent significant prolongation of recalcification, prothrombin and partial thromboplastin times. These effects reached a peak after 30 minutes while the thrombin clotting time was not significantly altered and was even shortened in the presence of highest concentration of zinc tested [1mg/mI]. Incubation of thrombin with zinc sulphate [150 micro g/ml] for up to 30 minutes did not affect significantly the action of thrombin. Incubation of the same concentrations of zinc sulphate with fibrinogen produced non clotting of fibrinogen after 0- minutes. Addition of rising concentrations of zinc sulphate to rat PRP produced inhibition of ADP- induced platellet aggregation. On the other hand, collagen - induced aggregation was insignificantly inhibited in the presence of zinc. In contrast, in vitro additions of rising concentrations of magnesium sulphate [2-5 mg/ml] to pooled rat plasma exerted no effect on recalcification time immediately after addition [0- minutes], but after 5 minutes following incubation it produced significant shortening of recalcification time in all the doses tested. The prothrombin time showed a general trend of shortening, maximal after 5- minutes incubation. The results of partial thromboplastin times revealed clotting before addition of calcium chloride. The thromboplastin time also showed progressive shortening with rising concentrations of magnesium sulphate. When thrombin solution was exposed to magnesium sulphate [2.5 mg/ml] no effect on the activity of thrombin was seen for up to 30 minutes. Fibrinogen solution similarly exposed to the same concentration of magnesium sulphate did not show any significant effect on its clottability with thrombin for up to 30 minutes. Magnesium sulphate in the range of doses tested significantly enhanced platelet aggregation of PRP in response to both ADP and collagen, and the responses observed were not dose dependent. The mechanisms underlying the effects of these two metals on blood clotting and platelet aggregation are discussed

Effects of some trace elements on platelet function in rats

The present study portrays the effects of some elements, namely: iron, zinc, copper, magnesium and gold, on platelet count, PCV and platelet aggregation, 60 minutes following administration of the metal salts. Marked thrmobocytopenia was encountered in rats treated with ferrous sulphate while the platelet count was significantly changed with the other elements tested. The PCV was significantly increased following treatment with ferrous sulphate and large dose of gold chloride, but was insignificantly altered with the other elements As regards platelet aggregation, all metals tested, with the exception of magnesium caused significant inhibition of platelet aggregation was only significantly impaired following treatment with iron and gold, but was insignificantly altered following treatment with zinc and copper. On the other hand, treatment with magnesium resulted in enhancement of both ADP- and collagen-induced aggregation. The mechanisms underlying these effects are discussed