Octreotide Attenuates Acute Kidney Injury after Hepatic Ischemia and Reperfusion by Enhancing Autophagy

Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat. Octreotide pretreatment significantly preserved renal function and reduced the severity of renal injury. Moreover, octreotide alleviated inflammation and apoptosis in the kidney after HIR. Additionally, octreotide induced autophagy and autophagy inhibition with 3MA markedly reversed the renoprotective, anti-inflammatory and anti-apoptotic effects of octreotide after HIR. Finally, octreotide abrogated the activation of phosphorylation of Akt, mTOR and p70S6K in the kidney after HIR. Our results indicate that octreotide reduced renal injury after HIR due to its induction of autophagy. The enhancement of autophagy may be potentially linked to the octreotide mediated Akt/mTOR/p70S6K pathway deactivation and reduction of kidney inflammation and apoptosis after HIR

Seasonal and inter-annual variability in alkalinity in Liverpool Bay (53.5° N, 3.5° W) and in major river inputs to the North Sea

A critical factor controlling changes in the acidity of coastal waters is the alkalinity of the water. Concentrations of alkalinity are determined by supply from rivers and by in situ processes such as biological production and denitrification. A 2-year study based on 15 cruises in Liverpool Bay followed the seasonal cycles of changing concentrations of total alkalinity (TA) and total dissolved inorganic carbon (DIC) in relation to changes caused by the annual cycle of biological production during the mixing of river water into the Bay. Consistent annual cycles in concentrations of nutrients, TA and DIC were observed in both years. At a salinity of 31.5, the locus of primary production during the spring bloom, concentrations of NO x decreased by 25?±?4 ?mol kg?1 and DIC by 106?±?16 ?mol kg?1. Observed changes in TA were consistent with the uptake of protons during primary biological production. Concentrations of TA increased by 33?±?8 ?mol kg?1 (2009) and 33?±?15 ?mol kg?1 (2010). The impact of changes in organic matter on the measured TA appears likely to be small in this area. Thomas et al. (2009) suggested that denitrification may enhance the CO2 uptake of the North Sea by 25%, in contrast we find that although denitrification is a significant process in itself, it does not increase concentrations of TA relative to those of DIC and so does not increase buffer capacity and potential uptake of CO2 into shelf seawaters. For Liverpool Bay historical data suggest that higher concentrations of TA during periods of low flow are likely to contribute in part to the observed change in TA between winter and summer but the appropriate pattern cannot be identified in recent low-frequency river data. On a wider scale, data for the rivers Mersey, Rhine, Elbe and Weser show that patterns of seasonal change in concentrations of TA in river inputs differ between river systems