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Modulation of interleukin-6 by β2-adrenoceptor in endotoxin-stimulated renal macrophage cells. Background. Activation of the cAMP signaling pathway by means of β2-adrenoceptor agonists has been shown to up-regulate interleukin-6 (IL-6) gene expression and to stimulate IL-6 production in macrophage cells. However, whether β2-adrenoceptor activation can also modify the rate of IL-6 production in macrophage cells activated by the bacterial endotoxins has not yet been determined. Using renal resident macrophage cells treated with endotoxin, lipopolysaccharide (LPS), and β2-adrenoceptor agonist, terbutaline, we investigated the role of cAMP pathway, tumor necrosis factor (TNF)-α and mitogen-activated protein kinase (MAPK) pathway (p42/p44) in regulating IL-6 production. Methods. IL-6 protein, mRNA, and promoter activity were measured in these cells exposed to LPS (1 μg/ml) and/or terbutaline (10-9 to 10-6 m). Furthermore, the time course effects of terbutaline on cAMP, MAPK (p42/p44), and TNF-α release were evaluated in the cells. Results. Terbutaline at high concentrations (10-6 m) significantly up-regulated IL-6 by approximately 25% (P < 0.05), whereas at a lower concentration (10-8 m), it down-regulated IL-6 production by 42% (P < 0.05). Terbutaline (10-8 and 10-6 m) caused a concentration- and time-dependent stimulation of cAMP (P < 0.05) and TNF production (P < 0.05) and a time-dependent decrease in MAPK activity (P < 0.05). Following the addition of a cAMP inhibitor, IL-6 promoter activity was correlated with TNF-α levels and MAPK activity. Conclusions. A biphasic effect of β2-adrenoceptor agonist on IL-6 production in renal resident macrophage cells became apparent when LPS was exposed to the cells. The terbutaline-induced down-regulation of IL-6 gene production was mediated by an inhibitory... [ABSTRACT FROM AUTHOR]

Abstract: The aim of the present study was to quantify phenolic acids and flavonoids from Citrullus colocynthis roots (CCR), leaves (CCL) fruits (CCF) and compare the antioxidant and free radical scavenging activities of their extracts and major compounds. Reverse phase high performance liquid chromatography method was developed and validated for the simultaneous quantification of phenolic acids and flavonoids from ethanol and hexane extracts of CCR, CCL and CCF. The antioxidant activity of CCR, CCL and CCF extracts was investigated by measuring total phenolics, total flavonoids contents, DPPH free radical scavenging activity, inhibition of linoleic acid peroxidation and reducing power. The RP-HPLC analysis of C. colocynthis extracts revealed the presence of ferulic acid, vanillic acid, p-coumeric acid, gallic acid, p-hydroxy benzoic acid and chlorogenic acid being the major phenolic acids and quercetin, myricetin and catechin being the most prominent flavonoids compounds. The amounts of TP (3.07–18.6mg/g of dry plant material, measured as gallic acid equivalent) and TF (0.51–13.9mg/g of dry plant material, measured as catechin equivalent) were higher in ethanol extracts of CCL, followed by CCR and CCF. Ethanol extract of CCL exhibited the highest antioxidant and DPPH radical scavenging activities followed by ethanol extracts of CCR and CCF. However, only hexane extract of CCF showed considerable DPPH radical scavenging activity. The results suggested that CCR, CCL and CCF extracts showed a wide variability of their phenolic acids and flavonoids composition and antioxidant activity. [Copyright &y& Elsevier]

Abstract: In this study we employed both detrended fluctuation analysis (DFA) and multiscale entropy (MSE) measurements to compare the long-range temporal correlation (LRTC) of multifibre renal sympathetic nerve activity (RSNA) between conscious and anesthetized Wistar rats. It was found that both methods showed the obvious LRTC properties in conscious state. Moreover, the scaling exponent of the RSNA in conscious rats was significantly higher than that in anesthetized rats. The results of MSE analysis showed that the entropy values, derived from the conscious group, increased on small time scales and then stabilized to a relatively constant value whereas the entropy measure, derived from anesthetized animals, almost monotonically decreased. This suggests that the fractal properties of underlying dynamics of the system have been reduced by anesthesia. The results demonstrate that apparently random fluctuations in multifibre RSNA are dictated by a complex deterministic process that imparts “long-term” memory to the dynamic system. However, this memory is significantly weakened by anesthesia. [Copyright &y& Elsevier]

Abstract: This study investigated whether the α1-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P <0.05) by 40–50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110±2 versus 102±3 mmHg and renal blood flow was lower, 10.7±0.9 versus 18.9±0.1 ml/min/kg in the renal failure rats (both P <0.05). AMP, MeU and BMY 7378 decreased (all P <0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P <0.05) in the renal failure but not in the normal rats. These data showed that α1A- and α1D-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of α1B-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats. [Copyright &y& Elsevier]

Apoptosis is regulated by several pathways, such as caspases, mitogen activated protein kinase (MAPK) and cAMP/cAMP-dependent protein kinase A (PKA) cascade. This study investigated the effect of β2-adrenoceptor activation on Shiga toxin (Stx)2-induced apoptosis in renal tubular cells and the contribution of these signalling pathways. Cultured human adenocarcinoma-derived tubular cells were exposed to Stx2 (64 pg/mL) for 2–24 hr following the addition of the β2-adrenoceptor agonist (terbutaline) to the incubation medium. Stx2-induced apoptosis and its amelioration by β2-adrenoceptor activation was confirmed using DNA degradation assays and by flow cytometry for annexin V, mitochondrial membrane potential and caspase(-3 and -7) activity. Exposure of cells to Stx2 for 24 hr increased the DNA fragmentation to 11.6±0.9%, compared to 3.3±0.2% in control cells (P<0.05) but was decreased to approximately 5–7% (P<0.05) in the presence of terbutaline. Furthermore, Stx2-stimulated apoptosis, detected by TUNEL, annexin V and mitochondrial potential, was inhibited by terbutaline (P<0.05) which was prevented by cAMP-PKA inhibitors and a β2-adrenoceptor antagonist. However, inhibition of Stx2-mediated caspase activity by terbutaline was partially blocked by cAMP-PKA inhibitors. On the other hand, p38MAPK inhibition by terbutaline prevented Stx2-induced apoptosis and caspase activity through a cAMP-independent pathway via β2-adrenoceptor. These data indicate that β2-adrenoceptor activation can inhibit Stx2-induced apoptosis of the cells, which may be caused by a reduction in caspase activity through cAMP-PKA activation and the p38MAPK pathway. [Copyright &y& Elsevier]