L-arginine reduces tubular cell injury in acute post-ischaemic renal failure

Background. The pathophysiology of renal ischaemia, resulting in tubular cell injury and leading to acute renal failure (ARF), remains unclear. An ever-increasing number of investigations focus on a possible role of nitric oxide (NO) in regulating circulation during ARF. In this context, we investigated the influence of chronic stimulation or inhibition of NO synthesis, or both, on haemodynamic parameters, histology and plasma renin activity (PRA) after ischaemia-reperfusion injury of rat kidneys. Methods, Experiments were performed on adult, male Wistar rats. Before induction of ARF, a group of animals was treated with a NO synthesis inhibitor (L-NAME) and another group was treated with a precursor of NO synthesis (L-arginine). The animals received those substances for 4 weeks. Control groups received the same amount of tap water for 4 or 8 weeks and were divided into groups with ARF (4 weeks-ARF group and 8 weeks-ARF group) and a sham-operated group. Another group of rats was treated first with L-NAME and then with L-arginine in their drinking water, for 4 weeks for each of these two substances. All parameters were evaluated 24 h after the induction of ischaemic ARF or the sham operation. Results, Our results show that such long-term stimulation of NO release by L-arginine improved renal haemodynamics in the ischaemic form of ARF. Renal blood Bow (RBF) increased by 96% in the L-arginine-treated rats with ARF compared with the group with ARF alone. Inhibition of NO synthesis worsens renal haemodynamics after ARF. However, this aggravation can be reversed by L-arginine. The rate of water reabsorption was reduced in all groups with ARF, but this reduction was least in the group treated with L-arginine. The rate of Na+ reabsorption was reduced in all groups 24 h after renal ischaemia, but a significant decrease was observed after the inhibition of NO synthesis. Histological examination of the kidney specimens showed that morphological changes were least in the rats treated with L-arginine, when compared with all other groups with ARF. Nevertheless, the lesions were most prominent in the L-NAME + ARF group. In this group, the areas of corticomedullar necrosis were more widespread in comparison with other groups, especially the L-arginine group where only swelling of the proximal tubular cells was observed. Treatment with L-NAME was not accompanied by any significant alteration in the plasma concentration of angiotensin I (ANG I), while in the group treated with L-arginine ANG I had a tendency to decrease. Conclusions. Acute post-ischaemic renal failure may be alleviated by administering the NO substrate (L-arginine). NO acts cytoprotectively on tubular epithelial cells in ischaemia-reperfusion injury of rat kidney. Evidence of this comes from both histopathological findings and increased tubular water and sodium reabsorption. However, inhibition of NO synthesis (provoked by L-NAME) worsens renal haemodynamics and aggravates morphological changes after ARF. These aggravations can, however, be reversed by L-arginine

Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure

Background. The relative roles of endothelin (ET)-1 and angiotensin (ANG) II in post-ischaemic acute renal failure (ARF) have not been fully established so far. With the aim of contributing to this goal, we assessed in this study the effect of ANG II and ET-1 blockade on the course of post-ischaemic-ARF. Methods. Anaesthetized Wistar rats received i.v. either bosentan (a dual ET receptor antagonist; 10 mg/kg body weight) or losartan [ANG II type 1 (AT(1)) receptor antagonist; 5 or 10 mg/kg body weight] or both, 20 min before, during and 20 min after ischaemia. Rats in the control group received the vehicle via the same route. Survival and renal function were monitored up to 8 days after the ischaemic challenge, while haemodynamic parameters were measured 24 h after ARF. Results. Our results demonstrate that bosentan treatment has a more beneficial effect on experimental ARF than losartan. The survival rate was remarkably higher in bosentan-treated rats than in both rat groups treated with losartan. In the ARF group treated with bosentan, renal blood flow (RBF) was increased by 129% in comparison with the untreated ARF group, whereas in the losartan-treated ARF groups, RBF was only similar to35 or 38% higher than in control ARF rats. The glomerular filtration rate was markedly higher in bosentan-treated rats than in all other ARF groups on the first and second day after ischaemia. Tubular cell injury was less severe in bosentan-treated rats than in the control ARF rats, but in losartan-treated groups it was similar to that in the ARF group. Concurrent blockade of both ET and AT(1) receptors did not improve ARF because this treatment induced a marked decrease in blood pressure. Conclusions. These results suggest that ET-1 blockade is more efficient in improving the early course of post-ischaemic renal injury than ANG II inhibition, and that blockade of ET-1 might be effective in prophylaxis of ischaemic ARF

The Middle and Late Pleniglacial (Weichselian) malacofauna of the Zemun loess–paleosol sequence, Serbia

The aim of our study was to describe the succession of malacological assemblages along the exposed loess profile located in Belgrade, along the banks of the Danube River (municipality of Zemun). Deposits that belong to the composite loess unit L1 were sampled. Loess unit L1 included two subunits: L1SS1 (a Middle Pleniglacial subunit with two weakly developed initial pedogenic horizons) and L1LL1 (a Late Pleniglacial loess subunit). Three malacological zones were distinguished. Malacological results imply a change in climatic conditions and subsequently in vegetation structure. The molluscs indicate an environment with a moderate (warm and dry) climate and a mosaic vegetation type composed of grasslands and forest steppe. Gradual cooling was inferred within the Late Pleniglacial period. Our findings concur with the results of earlier studies indicating that the Zemun site and the adjacent area served as a transition zone between the refuge areas within the southeastern part of the Carpathian Basin during the Late Pleistocene

The provenance of Danubian loess

With one of the largest watersheds in Europe, draining complex geological terrains within the Alps, Bohemian Massif, Carpathians, Dinarides, and the Balkan Mountains, the Danube River valley has long been linked to the formation of thick loess deposits, particularly within the Middle and Lower Danube basins. However, uncertainty over the provenance of loess-palaeosol sequences along the Danube impacts our understanding of sediment generation mechanisms and hinders interpretation of paleoenvironmental proxies preserved in loess. To date, most of the studies investigating loess provenance in Europe have not attempted a standardised characterisation and synthesis of loess deposits with potential source rocks. Further, despite clear links identified between loess and rivers in Asia and Europe, detrital zircons have not yet been used systematically to investigate the relationship between loess and the fluvial sediments of the Danube and its tributaries. Finally, in European loess research, provenance fingerprinting has often been conducted using indirect approaches or bulk sample geochemical analyses, which have been shown to have a limited application in well mixed sedimentary bodies such as loess. This provenance study of loess along the Danube River integrates existing zircon U-Pb ages and Hf datasets for loess, rivers, and bedrock, with new loess zircon U-Pb and Hf results from loess sequences in Croatia, Serbia and Bulgaria. The results show that all surrounding mountain belts (i.e. the Alps, Bohemian Massif, Carpathians, Dinarides Alps, and Balkan Mountains) contribute primary sediment to loess deposits in the Danube valley via its modern tributary network. Critically sedimentary sources remain relatively homogenous along the river, with no apparent major change in source with tributary confluence, further highlighting the role of fluvial transport in homogenising sediment prior to final aeolian deposition. Whilst some small site variations can be observed, they are likely explained by contributions restricted to very local rock outcrops. Moreover, geomorphological results support floodplain sediments as the proximal sediment source and suggest that short-distance aeolian transport dominates sediment delivery to loess sequences, challenging distant sources hypotheses such as major Saharan sources. The identification of sediment sourced from lower elevation regions such as the Bohemian Massif, Dinarides, and Balkans, which did not support ice-caps, suggests that the role of glacial action in silt-size sediment production has been previously exaggerated. Therefore, the glacial and desert loess division inadequately separates and describes sediment generation processes. This research supports and furthers previous work, which suggests “mountain sourced and transported by-rivers” as a more appropriate term for the particles forming loess, at least in the Danube basin