Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-α was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-α in all groups. Curcumin significantly ameliorated the ischemiainduced alterations in serum TNF-α and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI., F.T. Hammad, S. Al-Salam, L. Lubbad., and Obsahuje seznam literatury
The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously in vestigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic an d tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28±0.36 vs. 0.39±0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical signif icance (0.18±0.05 vs. 0.10±0.02, P=0.07). The left renal FE Na was significantly lower in Group-2 (29.9±6.4 vs. 49.7±7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, and fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI., F. T. Hammad, S. Al-Salam, L. Lubbad., and Obsahuje bibliografii a bibliografické odkazy
Renin-angiotensin system (RAS) plays a key role in the regulation of renal function, volume of extracellular fluid and blood pressure. The activation of RAS also induces oxidative stress, particularly superoxide anion (O2-) formation. Although the involvement of O2- production in the pathology of many diseases is known for long, recent studies also strongly suggest its physiological regulatory function of many organs including the kidney. However, a marked accumulation of O2- in the kidney alters normal regulation of renal function and thus may contribute to the development of salt-sensitivity and hypertension. In the kidney, O2- acts as vasoconstrictor and enhances tubular sodium reabsoption. Nitric oxide (NO), another important radical that exhibits opposite effects than O2-, is also involved in the regulation of kidney function. O2- rapidly interacts with NO and thus, when O2- production increases, it diminishes the bioavailability of NO leading to the impairment of organ function. As the activation of RAS, particularly the enhanced production of angiotensin II, can induce both O2- and NO generation, it has been suggested that physiological interactions of RAS, NO and O2- provide a coordinated regulation of kidney function. The imbalance of these interactions is critically linked to the pathophysiology of salt-sensitivity and hypertension., L. Kopkan, L. Červenka., and Obsahuje seznam literatury
Photodynamic therapy (PDT) is now being used more frequently in carefully selected cases of malignancies. The drugs used for PDT are mostly derivatives of haematoporphyrine (HPD) and its active component photofrine II. Another compound prepared by total synthesis is meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4) but its application in human medicine was rejected because of its neurotoxicity. Our TPPS4 was prepared by the method of Busby et al. in the modification of Jirsa and Kakaë (1987). This product is purer and without neurotoxic effects. In this study, we concentrated our attention on the effect of TPPS4 on nephrotoxicity and its accumulation in some organs. As the parameters of toxic kidney damage we used urine levels of N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine levels, glomerular filtration rate (GFR) and proteinuria. TPPS4 was administered i.v. in a dose of 25 mg/kg b.w. The animals were observed for 21 days after drug application. Urine and blood samples were collected over 24-hour periods on days 0, 5 and 21. The serum creatinine level was significantly higher only on day 5 (65.0±1.46 /zmol/1 vs 56.5±2.69 ^mol/1 on day 0, p<0.05). There were no significant changes in GFR, proteinuria or NAG activity in the urine during the experiment. AST serum activity was increased. We determined the concentration of TPPS4 (pmol/mg w.w.) in rat organs on the 21st day after the injection. The concentration of TPPS4 was high in kidneys (30.8 ±5.5), liver (13.5 ±2.0), lungs (11.7 ±4.6) and spleen (9.7 ±1.5), while the concentration in heart and brain was low. We conclude that TPPS4 has the highest concentration in the kidney 21 days after its administration and does not exert any nephrotoxic effects during this period.