It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.
Focal Segmental Glomerulosclerosis (FSGS) is one of the most frequent glomerulopathies, and is considered a public health problem worldwide. FSGS is characterized by glomerular loss mainly due to in ammation and collagen bers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation. Its activation occurs in response to several growth factors and cytokines. In renal cells, STAT-3 has been related with disease progression. Considering this perspective, the present study evaluated the involvement of STAT-3 in an experimental model of FSGS induced by Doxorubicin (DOX). First, we described a novel FSGS model in Swiss mice that after DOX administration showed typical signs of kidney dysfunction like higher proteinuria. Since there were no studies of ADM nephropathy model in heterogeneous mice, we were the rst to evaluate the model in this lineage. Control animals treated with STAT-3 inhibitor (STATTIC) presented lower levels of albumin/creatinine ratio, glycosuria e proteinuria while DOX-injected mice showed higher levels. After analyzing some molecules involved in the STAT-3 signaling pathway, it was observed that STAT-3 blockade decreased levels of STAT-3, IL-6 and IL-6R, which remained elevated in DOX-administrated mice. Moreover, we detected that SOCS-3 (a regulator of STAT family) was up-regulated only in STATTIC-treated mice. Finally, histopathological analyzes showed that DOX-treated group had a signi cant increase in a tubulointerstitial brosis and tubular necrosis, which were not identi ed in both control and STATTIC groups. Thus, our results indicate that STAT-3 can have an important role in experimental FSGS induced by DOX and further studies are encouraged.
Focal Segmental Glomerulosclerosis (FSGS) is one of the most frequent glomerulopathies, and is considered a public health problem worldwide. FSGS is characterized by glomerular loss mainly due to inflammation and collagen fibers deposition. STAT-3 is a transcription factor associated with cell differentiation, migration and proliferation. Its activation occurs in response to several growth factors and cytokines. In renal cells, STAT-3 has been related with disease progression. Considering this perspective, the present study evaluated the involvement of STAT-3 in an experimental model of FSGS induced by Doxorubicin (DOX). First, we described a novel FSGS model in Swiss mice that after DOX administration showed typical signs of kidney dysfunction like higher proteinuria. Since there were no studies of ADM nephropathy model in heterogeneous mice, we were the first to evaluate the model in this lineage. Control animals treated with STAT-3 inhibitor (STATTIC) presented lower levels of albumin/creatinine ratio, glycosuria e proteinuria while DOX-injected mice showed higher levels. After analyzing some molecules involved in the STAT-3 signaling pathway, it was observed that STAT-3 blockade decreased levels of STAT-3, IL-6 and IL-6R, which remained elevated in DOX-administrated mice. Moreover, we detected that SOCS-3 (a regulator of STAT family) was up-regulated only in STATTIC-treated mice. Finally, histopathological analyzes showed that DOX-treated group had a significant increase in a tubulointerstitial fibrosis and tubular necrosis, which were not identified in both control and STATTIC groups. Thus, our results indicate that STAT-3 can have an important role in experimental FSGS induced by DOX and further studies are encouraged.
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