The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO–/–). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO–/– mice. The levels of urinary protein observed in the 5-LO–/– mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO–/– mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO–/– mice. However, 5-LO–/– mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.
Background/Aims: Leaves of Echinodorus macrophyllus (EM), from the Alismataceae family, have been used in Brazilian folk medicine for their anti-inflammatory and diuretic properties. In this work, the diuretic and nephroprotective activities of crude extracts of EM were evaluated. Methods: Normal Wistar rats were given 0.9% NaCl containing either EM (10–300 mg/kg), furosemide (13 mg/kg) or arginine vasopressin (0.2 mg/kg). Thereafter, the rats were individually housed in metabolic cages, and urine volume was measured every 30 min for a total of 3 h. Acute kidney injury was induced by gentamicin (GM, 80 mg·kg–1·day–1, b.i.d., 5 days). Along with GM, 0.9% NaCl (control) or EM (30 mg/kg) was given to the rats by gavage. Results: EM produced a dose-dependent reduction in urine elimination. EM was effective in reversing all GM-induced alterations such as polyuria and glomerular filtration rate reduction. The GM-induced morphological alterations were not observed when EM was given concomitantly with GM. Conclusion: This study provides evidence that EM possesses nephroprotective effect which indicates that EM may have therapeutic applications in GM-induced acute kidney injury.
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