Supplementation with n-3 polyunsaturated fatty acids to lipopolysaccharide-induced rats improved inflammation and functional properties of renal Na,K-ATPase.

Measurements of enzyme kinetics of renal Na, K-ATPase were used for characterization of ATP- and Na⁺-binding sites in rats that were subjected to 10 days of moderate inflammation that was induced by a single dose of Escherichia coli lipopolysaccharides (LPSs) at a dose of 1 mg kg⁻¹ body weight. We hypothesized that LPSs might initiate a malfunction of renal Na, K-ATPase, which is a key enzyme involved in regulation of sodium homeostasis in the organism. We also investigated the potential effect that fish oil (FO) has in the prevention of Na, K-ATPase alterations by administering FO daily at a dose of 30 mg kg⁻¹. Alone, LPS elevated the level of C-reactive protein by more than 500% and free radicals by 36% in plasma, as indicated by an increased level of malondialdehyde. The Na, K-ATPase was slightly altered in the vicinity of the ATP-binding site as suggested by the 9% increase of the concentration of ATP necessary for half-maximal activation of the enzyme, thus indicating a deteriorated binding of ATP as a consequence of inflammation. Daily supplementation of FO partly attenuated LPS-induced injury, as observed by a significant decrease in the plasma levels of C-reactive protein and free radicals, hence maintaining the activity of renal Na, K-ATPase to the level of healthy control animals. In conclusion, our findings showed that FO prevented an excessive malondialdehyde production in LPS-treated animals and stabilized renal Na, K-ATPase.

Ischaemia/reperfusion-induced organ injury in low dose streptozotocin diabetes.

OBJECTIVES: The influence of low dose streptozotocin diabetes on intestinal and vascular injury induced by mesenteric ischaemia/reperfusion (I/R) was studied in rats. The role of reactive oxygen species (ROS) in the exacerbation of ischaemic/postischaemic damage in diabetes was addressed. METHODS: Diabetes was induced by i.p. injection of 3 x 30 mg/kg streptozotocin and after 5 weeks male Wistar rats underwent 60 min ischaemia followed by 30 min reperfusion of the superior mesenteric artery (SMA). The extent of intestinal haemorrhagic injury was assessed macroscopically. Relaxation to acetylcholine of precontracted SMA rings was tested. Chemiluminescence (CL) enhanced by luminol of tissue samples excised from the ileum and SMA was measured. RESULTS: In diabetic rats I/R-induced intestinal injury was significantly more pronounced compared to non-diabetic rats (63.6% potentiation). Decreased endothelial-dependent relaxation of diabetic SMA was not further influenced by I/R. Diabetes itself did not change the CL response of SMA and there was a similar CL increase in the diabetic group with I/R as in the controls. In the intestinal samples CL response was suppressed and I/R only mildly increased CL in the diabetic group. CONCLUSIONS: Diabetes renders the intestinal tissue more vulnerable to the effects of I/R. Endothelial-dependent relaxation of diabetic SMA was not further worsened by I/R. CL responses showed a different involvement of ROS in diabetic intestinal versus vascular tissue.

Effect of prenatal phenytoin administration on the fine structure of rat myocardium and aorta.

Phenytoin (PHT) is an antiepileptic drug known to have teratogenic effects. The aim of this study was to examine the ultrastructure of the left ventricle, the left atrium, and the aorta of 3-month-old offspring and 4-month-old mother animals after oral PHT (150 mg/kg/day) administration to Wistar/DV rats on days 7-18 of gestation. Electron microscopy of the myocardium revealed a heterogeneous population of cardiomyocytes with conventional architecture, and hypoxia/ischemia-like subcellular changes. Cardiomyocytes of offspring hearts were more vulnerable to PHT administration compared with the mother animals. Atrial cardiomyocytes of both mother animals and offspring were less affected by PHT than the ventricular ones. In the myocardium, both interstitial fibrosis and injury of capillaries were noted. Electron microscopy of the aorta revealed a higher resistance of maternal endothelial and smooth muscle cells to PHT compared with offspring cells. Nuclei of endothelial and smooth muscle cells showed pronounced mitotic activity with one and/or two hyperactive nucleoli, more frequently observed in offspring. PHT administration resulted in aortic arteriogenesis in both offspring and mother animals. Interestingly, bundles of myocardial fibers consisting of ischemia-like altered cardiomyocytes with own capillary network were noted in off-spring aortic adventitia. These results are indicative of harmful effects of PHT on rat myocardium and aorta.