protective effect of antioxidants on renal ischemia-reperfusion injury in the rat

Renal ischemia-reperfusion [I/R] is of clinical interest because of its role in renal failure and also in renal graft rejection. There is increasing evidence to suggest that reactive oxygen species [ROS] play a role in the pathogenesis of I/R injury in the kidney. This study was designed to investigate the protective effect of some dietary antioxidants [garlic, vitamin E or vitamin A + Se [+2]] against the damage inflicted by [ROS] during renal I/R. Five groups of male albino rats were used in this study each composed of 10 rats. Group I: Sham-operated control group. Group II: I/R group [not treated] unilaterally nephrectomized after subjection of the left renal pedicle to 60 minutes of nontraumatic occlusion followed by 24 hours of reperfusion. Group III: the same procedure as group II but animals were preconditioned by adding garlic powder to their diet 80 mg kg[-1] daily for one month. Group IV: like group III but vitamin E [6.5 mg kg[-1]/d for one month] was supplemented to diet. Group V: like the two previous groups III and IV but vitamin A [7.9 mg/kg[-1]] and Se[+2] [50 microg/kg[-1]] were added daily to the rats' diet for one month. At the end of the reperfusion period, the rats were sacrificed. Malondialdehyde [MDA], Reduced glutathione [GSH] concentrations, superoxide dismutase [SOD], glutathione reductase and glutathione peroxidase enzymatic activities were determined in plasma and kidney homogenates of all groups. Serum creatinine and blood urea concentrations, were measured, for the evaluation of renal function. Also Na[+]-K[+]-ATPase was determined in kidney homogenates. Ischemic reperfused [l/R] animals demonstrated severe detonation of renal function and a significant renal oxidative stress. Pretreatment of animals with garlic, vitamin E or vitamin A + Se [2+] markedly attenuated renal dysfunction and oxidative stress as manifested by reducing blood urea, serum creatinine, MDA and restored depleted renal antioxidant enzymes. Na[+]-K[+]-ATPase activity, which was decreased in the I/R group, increased in the animals preconditioned with vitamins E and A + Se[2+]. From this it can be concluded that ROS play a causal role in I/R induced renal injury and supplementing the animals with garlic and/or other dietary antioxidants exerts protective effects. Therefore, it is recommended to supply patients expected to suffer from I/R renal injury with these antioxidants

On the pathogenesis of platelet dysfunction of undialyzed and hemodialysed chronic renal failure [CFR] patients

Patients with chronic renal failure CRF suffer form abnormalities of primary hemostasis due to platelet dysfunction. Dialysis improves platelet abnormalities but does not eliminate the risk of hemorrhage. Hemodialysis can even contribute to the bleeding through the continuous platelet activation induced by the interaction between blood and artificial surfaces. The aim is to study the changes in the biostructure of platelets in ESRD and the effect of HD on it, and to find its relation to its function. The platelet biostructure [total protein, total lipids, total carbohydrates, total phospholipids [PL], total cholesterol] and enzymatic activities [Na[+]-K[+]-ATPase, monoamine oxidase, [MAO] often healthy control, 15 undialyied CRF patients, and 15 hemodialyzed CRF patients [before and after dialysis] were studied. The results revealed an increase of total lipids, total PL concentrations and decrease in the activities of Na[+]-K[+]-ATPase, MAO of platelets of CRF compared to their healthy controls. After dialysis results as compared to those before dialysis revealed decreased concentration of total PL of the platelets and increased activity of Na[+]-K[+]-ATPase. Whereas if the results after dialysis were compared to those of healthy controls total lipids, PL, total cholesterol concentration and Na[+]-K[+]-ATPase showed significant increased values whereas MAO activity decreased significantly. Correlation studies showed insignificant correlation for all the parameters studied before or after dialysis as compared with the age of patients or duration of dialysis-in years. It may be concluded that the biochemical aberrations that were revealed form the present study concerning End Stage Renal Disease [ESRD] patients [dialyzed and undialyzed] may be looked upon as a causative factor in the well known physiological impairment of platelet function in uremia which appears not to be totally corrected by hemodialysis

Effect of renal denervatoin on the glomerular filtration rate [GFR] and tubular function

The renal nerves are the communicating link between the central nervous system [CNS] and the kidney, contributing importantly to homeostatic regulation, renal blood flow [RBF], glomerular filtration rate [GFR], renal tubular solute and water transport and hormonal release. In patho-physiological conditions, abnormal regulation of efferent nerve activity constitutes significantly to associated abnormalities of renal function which in turn are of importance in the pathogenesis of many diseases such as hypertension. Denervation is a method commonly used to study the role of renal nerves in the control of kidney function, also it is mandatory in cases of kidney transplantation and when using ganglion blockers. To study the effect of renal denervation on kidney function in dog, using unilateral renal Denervation and split urine collection model. The left kidney was denervated through an abdominal approach. Urine and blood samples were collected for six clearance periods [10 minutes each]. The following parameters were done: Urine flow rate Uv [ml/min/m[2] surface area]. GFR [ml/min/m[2]] by inulin clearance method [C[1n]] Urinary excretion rate for Na[+], K[+], Cl[-l] [U[Na+] V, U[K+] V, U[cl-]. V for denervated [DNX] and innervated [INN] kidneys. Percentage fractional excretion of Na[+] [%FE[Na+] was also calculated for both kidneys. Marked diuresis, natriuresis, kaliuresis, chloresis and increased% FE Na[+] and GFR for the denervated [DNX] kidney were found as compared to the innervated [INN] control. Renal denervation results in marked diuresis and solute loss in the acute stage, therefore it is recommended to compensate for these losses especially in the early stages of renal Denervation whether surgical as in kidney transplantation or pharmacological as by delivering ganglion blockers or a-adrenoceptor inhibitors for patients with hypertension, otherwise grave water and electrolyte imbalances may occur

Functional capacity of autotransplanted versus homotransplanted canine kidney after sodium chloride load

Immunosuppressive therapy and uremia complicate the mechanisms involved in renal functional changes after kidney transplantation. Glomerular filtration rate [GFR] is attenuated after renal ischemia, whereas it increases after denervation, both are important factors in renal transplantation. A defect in renal handling of Na[+] in response to volume expansion in some reports of renal transplantation was also recorded. The aim of the present work was to study the functional capacity of auto-and homotransplanted canine kidneys after a sodium chloride load. Four groups each comprising six mongrel dogs were used in the present study: Group I: autotransplanted animals where GFR and kidney excretory functions were investigated immediately after transplantation. Group II: Like group I but the investigations were performed 5 days after autotransplantation. Group III: Animals with homotransplantation were subjected to the same investigation, as before, immediately after the operation. Group IV: The group of donors of the kidney to group III. And the remaining kidney served as the control for that of group III whose two kidneys were taken off just before the transplantation. Inulin was infused I. V. to study inulin clearance [C[IN], normal saline was also infused for 60 min then 5% NaCl solution for another 60 min. [Na[+] load. Arterial blood and urine samples were collected by catheter inserted in femoral artery and ureters of transplanted and control animal and the following parameters were investigated: Urinary excretion rate v C[IN] urinary excretion rate for Na[+], Cl[-] and K[+] [UE[Na]+, UE[cI-]- and UE[k], fractional excretion of Na[+] [FE[Na]+%] for group I, II, III and IV of animals [UK[Nn] or K[+] group I, II, III, IV of animals. Two collection periods were done, the first [60 min] with normal saline infusion and the second [60 min] with saline load. There were decreased values for v GFR [IN] UE[Na+] and UE[K+] FE[Na+%] compared to control in group I, III, UE[CI-] of group I showed no significant change. After 5 days of autotransplantation [gp II] UE[Na+] and FE[Na+]% were significantly increased compared to their control, v and GFR decreased and UE[CI-]- and UE[K+] did not change significantly from their control. After infusion of NaCl load v of group III increased there was insignificant change of UE[Na+] and UE[K+] for group II and increase of FE[Na+]% and significant increase of all parameters, of group I with the exception of C[IN] which decreased. There was significant decrease of all other parameters of the 3 groups as compared to their controls. Transplanted kidneys [auto or homo] behave functionally different from that after ischemia or denervation. Transplanted kidney can excrete a saline load and increase its GFR inspite of denervation and ischemia and this may be attributed to some humoral factors concerned with rennin angiotensin system [RAS] or atrial natriuretic peptide [ANP] or attenuation of sympathetic nervous system control. Care should be directed to the fluid and electrolytes [especially [K+]] infused to patients immediately following auto-or homotransplantation

Effect of renal ischemia / reperfusion [I/R] injury on glomerular filtretion rate [GFR] and tubular functions

Renal ischemia reperfusion [I/R] injury is of great clinical interest because of its role in renal failure, renal graft rejection and potential future chronic renal complications. Ten mongrel dogs were the material of the present study. Animals were subjected to renal ischemia by clamping the left renal artery for 30 minutes. After releasing the artery clamp six clearance periods [10 min each] were allowed to determine in each period glomerular filtration rate [GFR] by determining the inulin clearance [C[IN]], urinary flow rate [v], urinary excretion rate [UE] for Na[+], K[+], Cl[-],% Fractional excretion of sodium [%FE[Na]+], for both the ischemic left kidney and contralateral control kidney. The ischemic / control ratio [I/C] was determined for all the above parameters determined. v, UE[K+] decreased during the first collection period after reperfusion [10 min]. v increase markedly after that. GFR [C[IN]] and UE[K+] decreased also during the remaining 5 collection periods [50 min]. UE[Na+], UE[CI-] and FE[Na]% increased dramatically allover the collection periods [60 min]. The mechanisms of these changes were discussed. Gradual renal reperfusion and pre and post administration of antioxidants and anti-inflammatory drugs are recommended to ameliorate the deleterious affects ofl/R on the structure and function of the kidney

Functional significance of lipid changes under the effect of inhalational anesthetics

Small concentrations of inhaled anesthetics can induce type II pneumocytes dysfunction and affect surfactant production and exacerbate oxidant mediated lung injury. The aim of the present work was to study the interrelationship between alveolar surfactant lipid composition and that of the lung tissue aiming to understand the sequence of events in the pathogenesis and pathophysiology of acute lung injury [ALI] after inhalation anesthesia. 60 albino rats were used in this study. Lipids were extracted from the lung tissue and alveolar surfactant obtained by bronchoalveolar lavage from rats which were subjected to 1-2% halothane or nitrous oxide anesthetics. The following parameters were determined on the extracted lipids: total lipids [TL], triglycerides [TG], total cholesterol [T-ch], total free fatty acids [FFA], total phospholipids [TPL], phospholipids fractions, lecithin [phosphatidyl cholin Pc], lysolecithin, cephalin [phosphatidyl ethanol amine PI] and sphingomyelin. I- Effect of halothane In the surfactant: Halothane decreased all parameters studied with the exception of FFA and sphingomyelin which was increased compared to controls. Cephalin did not change. However, in the lung FFA, lecithin and lysolecithin increased while all other parameters decreased. II- Effect of nitrous oxide [N[2]O]: In the surfactant: All parameters also decreased except lysolecithin, cephalin and sphingomyelin, which were increased. However, FFA did not change significantly from controls. In the lung: Lecithin, lysolecithin and FFA increased whereas the other parameters decreased. Halothane and N[2]O differ as regards their effect on the lipid profile of the surfactant or lung tissue. The functional significance of the alteration was discussed

Effect of hemodialysis on hexose monophosphate pathway of red blood cells in end stage renal disease patients

To evaluate the role of hemodialysis [HD] on the correction of hexose monophosphate pathway [HMP] in chronic hemodialyzed patients. Ten end stage renal disease [ESRD] patients on chronic hemodialysis were selected from the nephrology unit of Medical Research Institute. All patients were on maintenance HD. [Three times per week for more than one year]. Hemoglobin [Hb] concentration, lipid peroxides as malonyldialdehyde [MDA], glutathione reductase [GR], glutathione peroxidase [GPX], glucose 6-phosphate dehydrogenase [G6PD], oxidized glutathione [GSSG] and reduced glutathione content [GSH] were estimated in erythrocytes. In addition, plasma creatinine was determined. All these parameters were estimated before and after haemodialysis session. Mean plasma creatinine was significantly decreased after haemodialysis. Mean erythrocyte lipid peroxides and GR were significantly increased after haemodialysis while GPX enzymatic activity was significantly decreased after haemodialysis. The above changes may indicate that HD enhances the oxidative-antioxidant defense system, but with no improvement of the anemia or correction of HMP pathway. The use of vitamin E coated membranes in the haemodialyzers and administration of antioxidants to hemodialyzed patients is recommended

Pathophysiological effects of mobile phone radiations on the brain: an experimental study

The increased use of mobile phone worldwide has focused interest on the possible effects of radiofrequency fields on health. However, until now no satisfactory mechanism has been proposed to explain the biological effects of these radiations. Thus this study was undertaken in order to investigate the effect of radiations emitted from mobile phone on: Malonyldialdehyde [MDA], as a lipid peroxidation product, and serotonin concentrations, as well as the activities of acetylcholinesterase [AChE] and sodium-potassium ATP-ase [Na[+] K[+] ATP-ase] enzymes in the different parts of rats brain. The study was conducted on twenty adult male albino rats. Ten were exposed to radiations emitted from cellular phone [the experimental group] and ten rats were in the same exposure conditions but the mobile phone was turned off [the control group]. Na[+] K[+] ATP-ase enzymatic activity was significantly lower while MDA and serotonin concentrations were significantly higher in all studied brain parts of the experimental group. AChE was found to be significantly lower only in the cerebellum of the experimental group. These results support the interaction of radiofrequency fields of mobile phones with biological systems. Oxidative stress and diminished Na[+] K[+] P-ase enzymatic activity in addition to disturbance in serotonergic neurons and possibly cholinergic neurons, all may play a role in the mechanism of adverse effects of electromagnetic radiations. Further studies are needed so as to find the threshold level for exposure to electromagnetic field [EMF] that is not adverse to human health

Effect of dietary garlic supplementation on lipid profile, oxidant-antioxidant status and aortic mechanical properties in experimental atherosclerosis

Experimental atherosclerosis was induced in a group of chicken [1 day old] by feeding a standard chicken diet supplemented with 1% cholesterol for twelve weeks. Another group was given the same diet supplemented with garlic [80 mg/kg body weight/day] for twelve weeks. The third group received standard poultry diet and served as controls. The alterations of lipids, lipid peroxidation products and antioxidant parameters of plasma and liver as well as the changes in the mechanical properties of the arterial walls were investigated. Hypercholesterolemia, a significant increase in low density lipoprotein cholesterol [LDL-C], triglycerides [TG] and phosphatidylcholine phospholipid fraction [PC] together with the significant decrease in high density lipoprotein cholesterol [HDL-C], very low density lipoprotein cholesterol [VLDL-C], total phospholipids and lysophosphatidylcholine [LPC] percent, induced by cholesterol feeding, were almost corrected by garlic administration. Lipid peroxidation products concentrations were significantly higher in atherosclerotic chicken and returned to almost control values by dietary garlic supplementation. In a corollary fashion, pronounced effect of garlic on antioxidants including liver glutathione [GSH], glutathione peroxidase [GPx], glucose-6-phosphate dehydrogenase [G6PDH], superoxide dismutase [SOD] and plasma antioxidant activity, expressed as D[max] was clearly noticed through restoration of their levels towards normal values after impairment under hypercholesterolaemia. As regards the mechanical properties, ultimate strain [U.S] of the thoracic aorta was significantly increased in the atherosclerotic group of chicken while the tensile strength [T.S] decreased significantly. The inner diameter of both thoracic and abdominal aortae decreased significantly in atherosclerotic group of chicken. These changes were returned to almost control values by addition of garlic powder to diet. These results suggest that garlic supplemented diet corrected not only pathological, lipids and antioxidant parameters but also the mechanical properties of the aortae

Effect of noise stress on rat brain histopathology, ultrastructure and neurotransmitter activity

Exposure to noise can elicit generalized stress disturbances in the body by way of neuroendocrine mediation. The effect of exposure of a group of albino rats to noise produced by a full range loud speaker installed 50 cm directly above the animal cage producing a sine wave noise of 135 dB at 500 HZ for 3 hours daily for 7 days, was studied. Histopathological and electron microscopic [EM] examination of rat's cerebral cortex [temporal lobe], medulla oblongata and cerebellum and monoamineoxidase [MAO] and a cetyicholinesterase [AChE] enzyme activity changes in the same brain parts were recorded. The results revealed non specific degenerative reactions to stress caused by noise in exposed rats and decreased enzyme activity of AChE and MAO in the medulla oblongata and temporal lobe respectively. These changes may explain the mental, neurobehavioural changes caused by noise stress

Effect of osmotic stress of some cations, anions and saccharides on uremic red blood cells

Osmotic fragility curves for control and uremic RBC were constructed for 10 different salts, 5 monosaccharides and 3 disaccharides to demonstrate the osmotic behavior of uremic red cells to different cations, anions and sugars. Median osmotic fragilities [MOF] for Na+, K+, Ca2+, Cl-, HCO3-, lactate, glucose, mannose, and lactose for uremic cells were decreased compared with controls, whereas that for galactose was >4.6 times increased. Hemolytic curves for fructose, arabinose, sucrose and maltose were almost identical for both control and uremic cells with insignificant change [P >0.05] for their MOF. From these results it may be inferred that uremic cells are more resistant to hemolysis when they are subjected to osmotic stress for most of the ions and sugars tested. These results provided important insights into the effects of uremia on the RBCs membrane permeability and may have important implications for dialysis and carbohydrate intolerance in uremia

Osmotic fragility of normal human erythrocytes in solutions of different cations and anions

Osmotic fragility curves for normal RBCs bathed with each of four different cations [Na[+],K[+],Ca[2] and Mg[2+] and five different anions [Lactate, H[2]PO[-4], Cl[-],HCo[-3] and HPO[--4] were constructed The curves for cations were typical "S" shaped. The divalent cations [Ca[+2] and Mg[+2]] produced more hemolysis than monovalent ones [Na[+] and K[+]] at each osmolal concentration of the curves. HCO[-3] has the least hemozytic effect while lactate the greatest. Divalent phosphate [HPO[--4] has less hemolytic effect than monovalent one H[2]PO[-4]] at high osmolal concentrations [150-300 mosm/L], The reverse effect occurs at lower osmosal concentrations [50-150 mosm/L], It is not only the total osmotic pressure [O.P] of the solution or the diameter of the ion but also the ion charge and the presence or absence of specific ion which determines the osmotic behaviour of the cell

Biochemical studies on blood platelets of chronic renal failure patients and their relations to impairment of platelet function

Abnormal bleeding is a major complication of chronic renal failure. Among the multiple causes of this defect is impaired platelet function as reduced platelet adhesiveness defective aggregation by thrombin and adenosine diphosphate, and inhibition of release reaction. The aim of this study was to find a correlation between impaired platelet function and changes of the biochemical structure of the plaselets. The platelets of 15 patients with chronic renal failure and ten normal subjects [controls] were studied for total proteins, lipids, phospholipids, cholesterol and total carbohydrates, and protein components separated by electrophoresis. Also the enzyme activities of Na[+]-K[+]-Mg[+2] adenosine triphosphatase and monoamine oxidase were studied. The results showed increased concentration of total lipids, phospholipids and a qualitative change in protein components of uremic platelets. On the other hand, the activities of Na[+]-K[+]-Mg[+2] adenosine triphosphatase and monoamine oxidase were decreased. These results were discussed in the light of their effect on platelet physiological functions

Enzyme activity changes in the issues of rats with experimental acute uraemia, 1 - the kidney

Acute uraemia was induced in Swiss albino rats by bilateral ureteral ligation. The histopathological and histochemical enzymatic changes of uraemic kidneys were studied 48 hours after induction of uraemia. Alkaline phosphatase [Alk. P.] and succinic dehydrogenase [S.D.] enzymes showed diminished activity in the proximal and distal convoluted tubules whereas acid phosphatase [Ac. P.] and alpha-esterases enzymes' activity did not change from normal. These enzyme changes reflect cellular damage in general and disturbance of TCA cycle with consequent disturbance in cellular respiratory functions. This led to the recorded cloudy swelling in the proximal convoluted tubules