RESUMO
Chronic diabetes mellitus (DM) can lead to kidney damage associated with increased reactive oxygen species (ROS), proteinuria, and tubular damage. Altered protein expression levels of transforming growth factor-beta 1 (TGF-ß1), fibronectin, and renal NADPH oxidase (NOX-4) are associated with the profibrotic phenotype in renal tubular cells. NOX-4 is one of the primary sources of ROS in the diabetic kidney and responsible for the induction of profibrotic factors in collecting duct (CD) cells. The renal medulla is predominantly composed of CDs; in DM, these CD cells are exposed to high glucose (HG) load. Currently there is no published literature describing the expression of these markers in the renal medulla in male and female mice during the early phase of DM, or the role of NOX-4-induced ROS. Our aim was to evaluate changes in transcripts and protein abundances of TGF-ß1, fibronectin, and NOX-4 along with ROS levels in renal medullary tissues from male and female mice during a short period of streptozotocin (STZ)-induced type 1 DM and the effect of HG in cultured CD cells. CF-1 mice were injected with or without a single dose of STZ (200 mg/kg) and euthanized at day 6. STZ females showed higher expression of fibronectin and TGF-ß1 when compared to control mice of either gender. Interestingly, STZ female mice showed a >30-fold increase on mRNA levels and a 3-fold increase in protein levels of kidney medullary NOX-4. Both male and female STZ mice showed increased intrarenal ROS. In primary cultures of inner medullary CD cells exposed to HG over 48 h, the expression of TGF-ß1, fibronectin, and NOX-4 were augmented. M-1 CD cells exposed to HG showed increased ROS, fibronectin, and TGF-ß1; this effect was prevented by NOX-4 inhibition. Our data suggest that at as early as 6 days of STZ-induced DM, the expression of profibrotic markers TGF-ß1 and fibronectin increases in renal medullary CD cells. Antioxidants mechanisms in male and female in renal medullary tissues seems to be differentially regulated by the actions of NOX-4.
RESUMO
Mining in Ecuadorian territory comprises three stages of Ecuadorian history: pre-Columbian, colonial, and republican times. In its beginnings, this activity did not have regulations or a legal foundation. The first Mining Law dates back to 1830, and it has been modified until the most recent update in 2009. The Andean region consists of 10 provinces, 9 of which have registered gold concessions, the most important of which are Loja, Azuay, and in recent years, Imbabura and Pichincha, which are the provinces with the highest number of reported concessions. The objective of this study focused on analyzing the historical and current situation of Artisanal and Small-scale Mining (ASGM) and the emergence of large-scale (industrial) mining. For the elaboration of this study, different methodological techniques were used, such as literature review, field interviews, and expert judgment validation. The main findings show that the provinces of Loja, Azuay, Imbabura, and Pichincha are the most conflictive areas in the region due to the impacts caused by mining activities. In socio-economic terms, there are conflicts between inhabitants in favor and against these activities and problems associated with human health. In environmental terms, the findings suggest historical contamination of water sources by heavy metals, which has altered the surrounding aquatic and terrestrial systems. Finally, the study concludes that implementing public policies should be promoted to balance socio-economic and environmental aspects in gold mining activities in the Andean region of Ecuador, strengthening the use of new technologies and education to raise awareness of the serious effects of mining activities.
