Influence of daily oral prophylactic selenium treatment on the dibutyltin dichloride (DBTC)-induced pancreatitis in rats

Dibutyltin dichloride (DBTC) is an organotin compound used as model for acute and chronic pancreatitis. Oxidative stress is one of the mechanisms of propagation of acinar cell injury in acute pancreatitis. Selenium is an essential cofactor in the antioxidant glutathione peroxidase pathway. Selenium levels are described to be subnormal in patients with acute and chronic pancreatitis. The aim of our studies was to determine the prophylactic effect of Na-selenite [5 mg kg-1 body weight (b.w.) per os (p.o.) 7 days] on the pathogenesis and course of DBTCinduced pancreatitis. Male inbred rats (LEW-1W Charles River) of 150 g body weight were used in this study. Experimental pancreatitis was induced by intravenous administration of 6 mg kg-1 b.w. DBTC in rats. Na-selenite was administered as daily oral dose of 5 mg kg-1 b.w. 7 days before induction of DBTC-pancreatitis. Malondialdehyde (MDA) was measured for monitoring levels of oxidative stress. Elimination of DBTC was reflected as tin concentration in bile and urine. Organ changes were indicated by serum parameters as well as histology. A prophylactic Na-selenite application significantly diminished MDA- and bilirubin concentration in serum, activities of lipase and transaminases as well as organ injuries compared to DBTC- treated rats in the absence of Naselenite. The prophylactic oral treatment with Na-selenite in the scope of DBTC-induced pancreatitis points to a reduced oxidative stress characterized by diminished MDA serum levels and a milder course of pancreatitis suggesting prophylactic substitution with Na-selenite to probably elicit beneficial effect on the clinical outcome in patients with endoscopic retrograde cholangiopancreatography (ERCP)

Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production

BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-alpha production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin

Bayesian Consensus

Tree file containing the consensus results of Bayesian analyses

RAxML Bootstrap Topology

This is the tree file containing the results of Maximum Likelihood analyses in the program RAxM

Data from: Cryptic diversity and population genetic structure in the rare, endemic, forest-obligate, slender geckos of the Philippines

Recent studies of forest lizards in Southeast Asia have highlighted spectacular morphological and cryptic genetic diversity in several poorly known clades. Unfortunately, many of the included species have microhabitat preferences for forested environments, and therefore they are threatened by extensive forest destruction throughout the region. This is particularly true in the Philippines, an archipelago with a strikingly high proportion (84%) of endemic geckos. Abundances inferred from historical museum collections suggests that we are in a critical period where apparent declines in population viability and species’ abundance have taken place faster than the growth in our understanding of alpha diversity. This phenomenon is exemplified in the exceedingly rare Philippine slender forest geckos of the genus Pseudogekko. Most of the known species are rarely encountered by field biologists, and species boundaries are unclear; this poor state of knowledge impedes effective conservation measures. Using the first multilocus phylogeny for these taxa, and phylogenetic and population genetic approaches, we elucidate evolutionary lineages and delimit species-level conservation targets in this unique radiation of endemic Philippine geckos. The results support the presence of widespread cryptic diversity in the genus, providing a framework for the re-evaluation of conservation priorities aimed at protecting these rare, forest-obligate species

Data Alignment

This is the alignment file for the molecular dataset used in the study. A character set is listed at the bottom of the alignment providing gene and tRNA information