association between nitrate contamination of drinking water and changes in methemoglobinemia and other hematological parameters in young and adult male rats

The objective of this investigation was to study the effect of prolonged exposure to nitrate polluted drinking water on blood methemoglobin [Met-Hb] level and other hematological parameters, as well as nitric oxide [NO] level in serum and urine [measured as indicator for nitrate toxicity] in male rats of two different ages, young [3 weeks-old] and adult [12 weeks-old]. Rats were administered sodium nitrate in drinking water at concentrations [100 mg/L = 8.7 mg/Kg, 250 mg/L=21.7 mg/Kg or 550 mg/L 47.7 mg/Kg] daily for four months. The obtained data showed a dose dependent reduction in the values of erythrocytes, leucocytes and platelets count, as well as jib content, Het%, MCV, NCH, MCHC and serum total iron in all nitrate exposed rats, with the marked decreases being occurred among the young animals. On contrary, nitrate exposure revealed a dose dependent increase in blood Met-Fib level, as well as NO production in serum and urine of all tested rats, however the young rats were more affected than the adult ones at different nitrate concentrations. This indicated that prolonged exposure to water nitrate pollution is a risk factor for developing increased Met-Hb level and the other hematological disorders in all the rats groups, particularly the when exposure started at young age which may contribute to the excess production of NO in response to nitrate exposure

Biochemical-molecular markers in unilateral ureteral obstruction

Congenital obstructive nephropathy is the primary cause of end-stage renal disease in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. Obstructive uropathy effects -decline in the plasmatic renal flow and glomerular filtration rate, interstitial infiltrate of leukocytes, significant decrease of the urine concentration, loss of the capacity to concentrate urine as well as fibrosis and apoptosis- are a consequence of a variety of factors that work in complex ways and are still not fully understood. Mediators as angiotensin II, transforming growth factor-beta(TGF-beta) and nitric oxide (NO) have been implicated in congenital obstructive nephropathy. The renin-angiotensin system is regulated in different ways, affecting both renal structure and function, and that it in turn depends upon the duration of the obstruction. On the other hand, the role of nitric oxide in renal injury remains somewhat controversial due to the fact that it can exert opposite effects such as cytoprotective and prooxidant / proapoptotic efects as well as proinflammatory and anti-inflammatory effects. In addition, reactive oxidative species (ROS) might contribute to the progression of renal disease. During unilateral ureteral obstruction induced uncoordinated and aberrant growth may lead to the loss of cellular phenotype and apoptosis. Promoting inflammatory responses, the oxidizers can regulate the adherence of certain molecules and proinflammatory mediators, transcription factors and fibrogenic cytokines, that are clearly involved in the progression of renal disease. The congenital obstructive nephropathy is characterized by tubular atrophy, cellular proliferation, apoptosis and fibrosis; immature kidney is more susceptible than adult kidney to showing the above mentioned alterations.

Renin angiotensin aldosterone system and fibrinolytic activity in experimentally induced diabetic and hypertensive rats

Many evidences pointed to certain relations between renin angiotensin aldosterone system [RAAS] and endogenous fibrinolytic system. To examine the effect of low salt supplement, as an activator to endogenous RAAS on plasma fibrinolytic function in alloxan diabetic L-NAME induced hypertensive ncphritic rats in the presence or absence of angiotensin converting enzyme inhibitor [ACEI] and/or aldosterone antagonist. Diabetes was induced in male Wistar rats by a single intraperitoneal [i.p] injection of alloxan [150 mg/kg]. Rats were received low salt supplement [0.08% NaCI] and N[G]-nitro-L-arginine methyl ester [L-NAME, 0.1 mg/ml] in the drinking water during the experimental periods. Treatment of diabetic hypertensive nephritic rats with ACEI [mocxipril hydrochloride, 7 mg/kg body weight daily and orally], aldosterone antagonist [spiranolactone, 25 mg/kg body weight daily and orally] or their combined administration for 6 weeks. Glucose, creatinine, sodium, potassium, aldosterone, ACE activity, transforming growth factor-beta 1 [TGF-beta] were determined in serum, whereas, renin, plasminogen activator inhibitors [PAI-1 were estimated in plasma. In urine nitric oxide [NO] concentration was evaluated and total. DNA and RNA were recorded in kidney tissues. During low salt intake, activation of the RAAS was monitored through observed significant Increase in serum alciosterone, sodium, potassium, and ACE activity. Impairment of renal function following diabetes and L-NAME administration was manifested By increase in serum glucose, mean arterial pressure [MAP] heart rate [HR]. serum creatinine and low urinary NO level, these data demonstrated that activation of RAAS in diabetic hypertensive nephritic rats significantly increased PAI-1 activity, TGF-beta1 and dry thrombus weight. It markedly decreased total DNA contents in kidney homogenate. Interruption of the RAAS with the ACEI, aldosterone antagonist or their combined administration lot 6 weeks significantly decreased PAl-1 activity TGF-beta1 and thrombus weight [fibrinolytic actvity]. However urinary NO, kidney content of total DNA showed significant increase. Combined form therapy has a better effect regarding PAI-1 TGF-beta 1 and NO than monotherapy. Data obtained provides an evidence of direct functional association between the RAAS and the fibrinolytic system in rats. This may help to elucidate possible mechanisms by which ACE inhibition and aldosterone antagonist exerts antagonist exerts vasculoprotective effects and reduce the risk of renal atherothromhotic events closely related to uncontrolled diabetes

Assessment of urinary endothelin-1 and nitric oxide levels and their relationship with clinical and pathologic types in primary glomerulonephritis

To determine the relationship between the urinary endothelin (ET-1), nitric oxide (NO) levels and the clinical, pathologic types of primary glomerulonephritis (GN) patients, urinary levels of ET-1 and NO were detected in 27 patients with biopsy-proven primary GN and 12 normal controls by radioimmunoassay and by copper-plated and cadmium column reduction assay, respectively. The results showed that urinary ET-1 levels in the patients with primary GN were significantly higher than in normal controls (p < 0.01), while the urinary ET-1 levels in patients with moderate mesangial proliferation GN were significantly higher than those in patients with mild mesangial proliferation GN (p < 0.05). Urinary ET-1 levels in patients whose clinical feature was nephrotic syndrome were found to be higher than in patients whose clinical feature was nephritic syndrome. However, urinary NO levels were to the contrary (p < 0.05). The ratio of ET-1/NO in primary GN patients was significantly higher than that in normal controls, and it positively correlated with the 24-hour urinary excretion of protein. These results suggest that urinary ET-1 levels are related to the proliferation of mesangial cells. The imbalance between ET-1 and NO may be related to the pathogenesis of primary GN and the occurrence of proteinuria.

Study of increased urinary nitrite excretion as a diagnostic marker for minmal change nephrotic syndrome

Urinary excretion of nitrite [a stable metabolite of nitric oxide] was estimated in children with nephrotic syndrome and healthy children as a control group. Urinary nitrite level was significantly increased in patients with nephrotic syndrome when compared with control group [p < 0.001]. It was significantly higher in patients with minimal change nephrotic syndrome than control group [p < 0.0001]. In contrast it showed no significant change in patients with non minimal change nephrotic syndrome when compared to control group [p > 0.05]. No significant difference could be detected in urinary nitrite level between the attack and remission in patients with minimal change nephrotic syndrome. We concluded that estimation of urinary nitrite level can be considered as a diagnostic marker for minimal change nephrotic syndrome. It is an easy rapid and non invasive test to discriminate it from other causes of nephrotic syndrome

Endothelin-1 and nitric oxide in children with renal hypertension

Plasma and urinary endothelin-1[ET-1] and nitrate [NOx] as an index of nitric oxide generation were measured in 27 hypertensive children with renoparenchymal diseases, 15 normotensive children with renoparenchymal diseases and 20 healthy control children of matched age and sex. The mean value of plasma ET-1 concentration was significantly higher in hypertensive children with renoparenchymal diseases than both normotensive renal diseased children and normotensive healthy controls. Significant positive correlation was found between ET-1 levels and mean blood pressure in hypertensive children with renal diseases. The mean value of 24 hours urinary excretion of ET-1 was significantly higher in normotensive children with renal diseases than normotensive healthy controls, but significantly lower than hypertensive children with renal diseases. Significant increase in the plasma levels of NOx was observed among hypertensive renal diseased children than normotensive renal diseased children and normotensive healthy controls. Significant positive correlation was found between the levels of plasma ET-1 and plasma NOx in hypertensive renal diseased children

approach to the role of nitric oxide in hyperdynamic circulation in liver cirrhosis

Circulatory abnormalities arising in cirrhosis increased cardiac output and, possibly, heart rate coupled with reduced systemic vascular resistance, and possibly arterial pressure could result from peripheral vasodilatation. The locally acting vasodilator nitric oxide has recently been implicated as a possible mediator in the vasodilatation observed in cirrhosis. To investigate this hypothesis, total of 51 patients with liver cirrhosis were recruited in the present investigation, 14 had hyperdynamic circulation [HDC] and 37 had no manifestations of HDC the study also included 20 completely healthy controls. In each participant, serum and urinary nitric oxide [NO], urinary cyclic guanosine monophosphate [cGMP] excretions, serum endotoxin and C-reactive protein were determined. The study revealed significantly increased levels of serum NO, endotoxin and C-reactive protein as well as urinary excretions of NO and cGMP in patients with cirrhosis compared with controls. Patients with HDC had significant increase of all bioindices expcept C-reactive protein. Significant positive correlation existed between urinary CGMP, urinary NO, serum NO, endotoxin C-reactive protein. These findings would indicate that bacterial endotoxin rather than cytokines induce NO synthase expression in vessel walls with sustained NO release. The released NO through activation of guanylate cyclase, leads to increased intracellular cGMP concentrations and induces vasodilatation and hypotension. Inhibition of NO synthesis in these patients could be achieved by reduction of endotoxaemia through sterilization of the intestine. This would result in restoration of sensitivity to vasoconstrictors and reverse the haemodynamic abnormalities in liver cirrhosis