Role of the sympathetic nervous system in carbon tetrachloride-induced hepatotoxicity and systemic inflammation

Carbon tetrachloride (CCl4) is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS) in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL)-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2), and tumor necrosis factor-α (TNF-α)], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response

Diversity, Ecology and Biogeochemistry of Cyst-Forming Acantharia (Radiolaria) in the Oceans

Marine planktonic organisms that undertake active vertical migrations over their life cycle are important contributors to downward particle flux in the oceans. Acantharia, globally distributed heterotrophic protists that are unique in building skeletons of celestite (strontium sulfate), can produce reproductive cysts covered by a heavy mineral shell that sink rapidly from surface to deep waters. We combined phylogenetic and biogeochemical analyses to explore the ecological and biogeochemical significance of this reproductive strategy. Phylogenetic analysis of the 18S and 28S rRNA genes of different cyst morphotypes collected in different oceans indicated that cyst-forming Acantharia belong to three early diverging and essentially non symbiotic clades from the orders Chaunacanthida and Holacanthida. Environmental high-throughput V9 tag sequences and clone libraries of the 18S rRNA showed that the three clades are widely distributed in the Indian, Atlantic and Pacific Oceans at different latitudes, but appear prominent in regions of higher primary productivity. Moreover, sequences of cyst-forming Acantharia were distributed evenly in both the photic and mesopelagic zone, a vertical distribution that we attribute to their life cycle where flagellated swarmers are released in deep waters from sinking cysts. Bathypelagic sediment traps in the subantarctic and oligotrophic subtropical Atlantic Ocean showed that downward flux of Acantharia was only large at high-latitudes and during a phytoplankton bloom. Their contribution to the total monthly particulate organic matter flux can represent up to 3%. High organic carbon export in cold waters would be a putative nutritional source for juveniles ascending in the water column. This study improves our understanding of the life cycle and biogeochemical contribution of Acantharia, and brings new insights into a remarkable reproductive strategy in marine protists