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

Implication of insulin folate combined treatment on the relationship between hyperhomocysteinemia and nephropathy in STZ diabetic rats

To investigate the efficacy of folic acid supplementation and insulin administration as therapeutic intervention for hyperhomocysteinemia, nephropathy and hyperglycemic complications in streptozotocin diabetic nephrotic rats. Animals: Male Wistar rats obtained from Veterinary animal farm. Setting: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Design: Diabetes was induced in sixty male Wistar rats by single intraperitoneal [i.p.] STZ [50 mg/kg]. Diabetic rats were fed methionine overload diets for 30 days and subjected later to gradual doses of gentamycin [200 mg/kg] for 10 days for induction of nephrotoxicity. Diabetic methionine overload nephrotic rats [DMN] treated with insulin and/or folic acid [90 micro g] daily and orally for 4 weeks. Groups of age matched healthy animals [n = 10], diabetics [n = 8] and DMN rats [positive control, n =7] served as controls. At the end of the study, serum glucose, creatinine, insulin, folate, plasma tHcy, NO, lipid profile and the susceptibility of low density lipoprotein [LDL] to copper catalyzed oxidation were determined. Superoxide dismutase [SOD], reduced glutathione [GSH] and lipid peroxide expressed as malondialdehyde [MDA] were measured in kidney tissue homogenate. Histopathological examination of kidney slices were also determined. In DMN group, glucose, creatinine, tHcy, NO, susceptibility of LDL to oxidation, and renal MDA contents showed significant increase, whereas folate, renal GSH and SOD activities revealed marked reduction. Insulin treatment modulates the above mentioned parameters, however folic acid failed to affect serum glucose and lipid pattern. Combined form therapy has a better effect regarding reduction of tHcy as compared to insulin alone. Oxidative cell markers specifically oxidative susceptibility of LDL to oxidation, NO and SOD activities seemed to be greatly attenuated more than individual treatment. Finally, folic acid coadministration with insulin may limit the progression of the vascular nephropathy of kidney tissue and interstitial haemorrhage in comparison with diabetic and DMN rats. Hyperhomocysteinemia is mainly a consequence of renal insufficiency rather than diabetes and represents an inducer for vascular damage in respect to status and prognosis of renal failure. Folic acid may have a renoprotective effect augmenting the therapeutic efficiency of insulin through its effect on tHcy reduction and limitation of tissue toxicities originating from oxygen free radicals generation

use of new markers for the detection of liver damage in experimental rats administered certain heavy metals

Pollution either environmental or industrial becomes one of the most serious problems in this century. In a previous research dealing with the same subject, groups of male healthy workers were selected and recruited from some industrial locations [melting units of different metal factories]. Certain parameters were determined and the results obtained revealed that, neither serum liver enzymes, nor heavy metals level recorded any alterations. Fibronectin and chondroitin sulfate on the other hand, demonstrated significant increase which may be considered as an early marker for liver cirrhosis which may happen later on. The present work was suggested using experimental animals, which received the same heavy metals [Fe, Cu and Pb] for Certain periods aiming to support and confirm the previously observed clinical findings through the examination of liver tissues histopathologically