Polycyclic aromatic hydrocarbon concentrations, mutagenicity, and Microtox® acute toxicity testing of Peruvian crude oil and oil-contaminated water and sediment.

The oil industry is a major source of contamination in Peru, and wastewater and sediments containing oil include harmful substances that may have acute and chronic effects. This study determined polycyclic aromatic hydrocarbon (PAH) concentrations by GC/MS, mutagenicity using TA98 and TA100 bacterial strains with and without metabolic activation in the Muta-ChromoPlate™ test, and Microtox® 5-min EC50 values of Peruvian crude oil, and water and sediment pore water from the vicinity of San José de Saramuro on the Marañón River and Villa Trompeteros on the Corrientes River in Loreto, Peru. The highest total PAH concentration in both areas was found in water (Saramuro = 210.15 µg/ml, Trompeteros = 204.66 µg/ml). Total PAH concentrations in water from San José de Saramuro ranged from 9.90 to 210.15 µg/ml (mean = 66.48 µg/ml), while sediment pore water concentrations ranged from 2.19 to 70.41 µg/ml (mean = 24.33 µg/ml). All water samples tested from Saramuro and Trompeteros sites, and one out of four sediment pore water samples from Trompeteros, were found to be mutagenic (P < 0.001). One sediment pore water sample in Saramuro was determined to have a measurable toxicity (Microtox EC50 = 335.1 mg/l), and in Trompeteros, the EC50 in water and sediment pore water ranged from 25.67 to 133.86 mg/l. Peruvian crude oil was mutagenic using the TA98 strain with metabolic activation, and the EC50 was 17.18 mg/l. The two areas sampled had very high PAH concentrations that were most likely associated with oil activities, but did not lead to acute toxic effects. However, since most of the samples were mutagenic, it is thought that there is a greater potential for chronic effects.

Apparent mineralocorticoid excess syndrome: an overview

A síndrome do excesso aparente de mineralocorticóides (SEAM) resulta de defeito na 11b-hidroxisteróide desidrogenase tipo 2 (11b-HSD2). Esta enzima é co-expressa com o receptor mineralocorticóide (RM) nos rins e converte cortisol (F) em cortisona (E), seu metabólito inativo. Deficiência desta enzima permite que o cortisol não metabolizado se ligue ao RM, induzindo retenção de sódio, hipocalemia, supressão da APR e hipertensão. Mutações no gene que codifica a 11b-HSD2 são responsáveis pela forma herdada, mas um quadro clínico semelhante de SEAM ocorre durante ingestão dos bioflavonóides, alcaçuz e carbenoxolona, que são inibidores competitivos da 11b-HSD2. Redução na atividade da 11b-HSD2 pode explicar o aumento da retenção de sódio na pré-eclâmpsia, na doença renal e na cirrose hepática. Deficiência relativa de atividade da 11b-HSD2 pode ocorrer na síndrome de Cushing devido à saturação da enzima e explicar o estado de excesso mineralocorticóide que caracteriza a síndrome do ACTH ectópico. Redução da expressão placentária da 11b-HSD2 poderia justificar a ligação entre baixo peso ao nascer e hipertensão no adulto. Variabilidade polimórfica no gene HSD11B2 determina, em parte, a sensibilidade ao sódio, um preditor do surgimento da hipertensão no adulto. A SEAM representa um espectro de hipertensão mineralocorticóide cuja severidade reflete o defeito genético de base na 11b-HSD2; embora a SEAM seja uma doença genética, vários compostos exógenos podem provocar os sintomas pela inibição da 11b-HSD2. O excesso de substrato, visto na síndrome de Cushing e na produção ectópica de ACTH, pode sobrepujar a capacidade da 11b-HSD2 de converter F em E, levando a uma forma adquirida de SEAM.

Apparent mineralocorticoid excess syndrome: an overview.

Apparent mineralocorticoid excess (AME) syndrome results from defective 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol (F) to its inactive metabolite cortisone (E). Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, hypokalemia, suppression of PRA and hypertension. Mutations in the gene encoding 11beta-HSD2 account for the inherited form, but a similar clinical picture to AME occurs following the ingestion of bioflavonoids, licorice and carbenoxolone, which are competitive inhibitors of 11beta-HSD2. Reduced 11beta-HSD2 activity may explain the increased sodium retention in preeclampsia, renal disease and liver cirrhosis. Relative deficiency of 11beta-HSD2 activity can occur in Cushing's syndrome due to saturation of the enzyme and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome. Reduced placental 11beta-HSD2 expression might explain the link between reduced birth weight and adult hypertension. Polymorphic variability in the HSD11B2 gene in part determines salt sensitivity, a forerunner for adult hypertension onset. AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11beta-HSD2; although AME is a genetic disorder, several exogenous compounds can bring about the symptoms by inhibiting 11beta-HSD2 enzyme. Substrate excess as seen in Cushing's syndrome and ACTH ectopic production can overwhelm the capacity of 11beta-HSD2 to convert F to E, leading up to an acquired form of AME.