Biomedical subjects

Marina Aunapuu

Publications and source records attributed to Marina Aunapuu.

7 recordsLinked to original sources

PubMed2005

Morphological changes in experimental postischemic rat kidney. A pilot study.

The aim of our study was to investigate the changes in the early stages (at weeks 2 and 4) of experimental acute renal failure after short-time ischemia-reperfusion (I/R) compared with the impact of Losartan. Twenty male Wistar rats were divided into three groups: sham-operated rats (2 weeks), I/R groups (2 and 4 weeks); I/R and Losartan-treated groups (2 and 4 weeks). I/R was produced in adult rats by clamping the left kidney renal artery and renal vein for 40 min. The angiotensin II receptor antagonist Losartan was added to the drinking water (40 mg/l), and treatment was started on the first day after the I/R. Body weight, systolic blood pressure (SBP) and 24 h urine amount was measured every week. Urine amount and SBP was higher in I/R groups compared to sham-operated rats. Early stage acute renal disease was characterized by focal segmental glomerulosclerosis (FSGS) and interstitial fibrosis (IF) at weeks 2 and 4 after I/R. In the Losartan group, 2 weeks after the surgery, FSGS, IF and mesangial cell proliferation was decreased, but at week 4 these parameters showed a tendency to increase. Marked changes take place in tubular epithelial cells, especially in I/R groups. Angiotensin II receptor blocker AT1RA Losartan in the small dose (40 mg/l) had no effect on hypertension and urine excretion in the experimental I/R model. A pilot study revealed that tubular basement membrane thickness is markedly increased after I/R.

Animals↗

PubMed2005

Helicobacter pylori substantially increases oxidative stress in indomethacin-exposed rat gastric mucosa.

Helicobacter pylori (H. pylori) often play an important role in the pathogenesis of gastritis, peptic ulcer, and probably also gastric cancer. Reactive oxygen species (ROS) produced by this bacterium may be one of the crucial factors whereby oxidative stress can play a role in the pathogenesis of ulcer disease. The aim of this study was to assess ROS activity and glutathione redox status, a principal cellular redox sensor, in H. pylori-associated indomethacin-induced gastric ulcers in rats. Gastric lesion was produced by intragastric administration of indomethacin (7 mg/kg) for three days followed by administration of H. pylori suspension (density 10(9) colony forming units). Animals receiving indomethacin only or followed by administration of H. pylori suspension were sacrificed after 11 and 18 days. ROS activity was assessed by the level of lipid peroxidation (LPO) and the glutathione redox status by the ratio between oxidized and reduced glutathione (GSSG/GSH). Indomethacin did not significantly increase the level of LPO and the GSSG/GSH ratio. When H. pylori suspension was given together with indomethacin the LPO was increased both on days 11 and 18 and GSSG/GSH on day 18. H. pylori, thus, substantially increases glutathione redox ratio and lipid peroxidation in gastric mucosa, which may play an important role in the pathological mechanisms of this bacterium. The findings support the idea that dietary antioxidants could be beneficial in combination therapy for eradication of H. pylori.

Animals↗

PubMed2004

Low-dose radiation modifies the progression of chronic renal failure.

Previous studies have indicated that the application of low dose radiation to an arterial ligation has the potential to subsequently reduce or eliminate restenosis caused by smooth muscle cell proliferation. Sufficient kidney irradiation causes a radiation nephropathy and often leads to renal failure. In order to evaluate the effect of low-dose irradiation on the kidney we hypothesized that this particular therapy modifies renal injury in rats with renal ablation and subsequently slows the rate of the progression. For further clarification of the effect of irradiation at low doses, we determined proliferating cell nuclear antigen (PCNA) and monocyte chemoattractant protein-1 (MCP-1) expression in remnant kidneys after low-dose radiation. Adult Wistar rats (n = 10) were studied during the two weeks after renal ablation. The left kidney was irradiated 24 hours after an operation in anaesthetised animals with 3 Grey in a single dose. Ablated rats without irradiation (n = 9) served as nephrectomized animals group. Rats without surgery and without radiation (n = 10) served as healthy controls. Renal damage was assessed using the following parameters: urine protein excretion rate (UprotV, mg/day), awake systolic blood pressure (SBP, mm Hg), serum creatinine (SCr, micromol/l). The indirect immunofluorescence method was used for the detection of PCNA and MCP-1 expression. Glomerular and tubular immunostaining was scored semiquantitatively. Numerous PCNA positive cells and MCP-1 expression were present in the glomerulus and tubulointerstitium in nephrectomized rat kidneys. Low-dose radiation application was associated with a significant reduction in PCNA and low MCP-1 expression. This study shows that the application of low-dose irradiation has the potential to modify the progression of chronic renal failure in rats.

Animals↗

PubMed2004

Decrease in laminin content and protein excretion rate after five sixths nephrectomy and low-dose irradiation in the rat.

The effect of low-dose irradiation on laminin distribution and urine protein excretion in the remnant rat kidney has been studied. The rat remnant kidney formed after 5/6 nephrectomy is an experimental model of chronic renal failure. In the remnant kidney, focal segmental glomerulosclerosis is developed characterized by focal or segmental sclerosis in glomeruli, alterations in the tubules and thickening of the glomerular basement membrane. Low dose irradiation has been presumed to suppress sclerotic processes. In this study 24 male Wistar rats were subdivided into the nephrectomized group, nephrectomized and irradiated groups (1 or 3 Grey), and healthy control group. Animals were sacrificed at 2, 4 and 8 weeks after beginning the experiment. Laminin immunohistochemical staining was found along the tubular and glomerular basement membranes in all experimental groups, but with varying intensity. Laminin content in the basement membranes was decreased in early stages (week 2), especially after irradiation followed by increase during the later stages with relatively high levels at the end of the experiment (week 8). Irradiation at a dose of 3 Grey decreased protein excretion compared to the nephrectomized rats at all stages, while 1 Grey dose was ineffective. Based on decreased proteinuria we conclude that moderate low-dose irradiation has beneficial effects on the rat remnant kidney and that laminin in basement membranes is probably not the most crucial component in regulating membrane permeability.

Animals↗

PubMed2004

Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice.

Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK(2) receptor deficient (CCK(2) (-/-)) mice and assessed their mechanical sensitivity using Von Frey filaments, as well as the development and time course of mechanical hyperalgesia in a model of neuropathic pain. We found that CCK(2) (-/-) mice displayed mechanical hyposensitivity, which was reversed to the level of wild-type animals after administration of naloxone (0.1-10 mg/kg). On the other hand, injection of L-365260 (0.01-1 mg/kg), an antagonist of CCK(2) receptors, decreased dose-dependently, mechanical sensitivity in wild-type mice. The mechanism of reduced mechanical sensitivity in CCK(2) (-/-) mice may be explained by changes in interactions between CCK and opioid systems. Indeed, CCK(2) (-/-) mice natively expressed higher levels of lumbar CCK(1), opioid delta and kappa receptors. Next, we found that CCK(2) (-/-) mice did not develop mechanical hyperalgesia in the Bennett's neuropathic pain model. Induction of neuropathy resulted in decrease of lumbar pro-opiomelanocortin (POMC) gene expression in wild-type mice, but increase of POMC expression in CCK(2) (-/-) mice. In addition, induction of neuropathy resulted in further increase of opioid delta receptor in CCK(2) (-/-) mice. Gene expression results indicate up-regulation of opioid system in CCK(2) (-/-) mice, which apparently result in decreased neuropathy score. Our study suggests that not only pain sensitivity, but also mechanical sensitivity and the development of neuropathic pain are regulated by antagonistic interactions between CCK and opioid systems.

Animals↗

PubMed2004

Oxidative stress status in kidney tissue after losartan and atenolol treatment in experimental renal failure.

BACKGROUND/AIMS: Rats with subtotal nephrectomy (5/6NPX) rapidly develop systemic hypertension and proteinuria. The aim of our study was to evaluate the changes in oxidative stress parameters after 2 and 4 weeks of treatment with renin-angiotensin system (RAS)-blocking agent losartan and beta-blocking agent atenolol in experimental chronic renal failure (CRF). METHODS: After 5/6NPX, rats were immediately treated with losartan or atenolol. The lipid peroxidation (LPO) products malondialdehyde and 4-hydroxyalkenals and oxidized and reduced glutathione values were measured in the renal cortex tissue and in blood; isoprostanes in urine. RESULTS: There were no differences in the blood pressure values, serum creatinine levels or in daily proteinuria using both antihypertensive treatments. Losartan treatment lowered significantly LPO in kidney tissue after 2 and 4 weeks of treatment compared with untreated and atenolol-treated animals and induced the decrease of excretion of isoprostanes in urine at the end of the study. There was no ameliorating impact of losartan or atenolol observed in the blood status of oxidative stress in this period of time. CONCLUSION: In the early period of experimental CRF, losartan treatment but not atenolol treatment induces significant decline in LPO grade in the kidney tissue of nephrectomized rats. RAS blockade in the kidney influences local tissue LPO in a much greater extent than in blood.

Animals↗

PubMed2003

Ultrastructural changes in the remnant kidney (after 5/6 nephrectomy) glomerulus after losartan and atenolol treatment.

The aim of our study was to investigate the effect of losartan on the changes in the early stages (at week 4) of experimental chronic renal failure after 5/6 nephrectomy compared with the impact of atenolol. Attention was focused on the ultrastructural changes in the renal corpuscles. Twenty-seven male Wistar rats were divided into three groups: nephrectomized group, nephrectomized losartan-treated group and nephrectomized atenolol-treated group. Rats were kept in a climate-controlled facility, where animals were housed under standard conditions on a 12-hour light/dark cycle and fed with standard rodent chow. Angiotensin receptor antagonist losartan (180 mg/L) or beta-blocking agent atenolol (750 mg/L) was added to the drinking water and treatment was started on the first day after the operation. Systolic blood pressure and 24 hour protein excretion was measured every week. Nephrectomized rats had higher proteinuria and systolic blood pressure than the treated rats. Rats were killed 4 weeks after surgery. Early stage renal disease was characterized by glomerular hypertrophy and focal segmental glomerulosclerosis. The morphological study revealed that ultrastructural changes in the atenolol-treated group were smaller than those in the nephrectomized and losartan-treated groups. Glomerular basement membrane (GBM) thickness was significantly increased in losartan-treated (206.8 nm) and atenolol-treated (198.8 nm) rats compared to nephrectomized (169.2 nm) rats. The podocytes demonstrated hypertrophy and foot process effacement, especially in nephrectomized group. In conclusion, our results show that firstly, treatment with losartan and atenolol significantly increased GBM thickening and secondly, treatment with atenolol reduced ultrastructural changes in the podocytes.

Adrenergic beta-Antagonists↗