ATP-sensitive potassium channel blockage attenuates cisplatin-induced renal damage.

BACKGROUND: Cisplatin-induced renal damage was associated with an inflammatory process. ATP-sensitive potassium channels can be involved in neutrophil migration. This study evaluated the effects of glibenclamide, an ATP-sensitive potassium channel blocker, on cisplatin-induced renal damage. METHODS: A total of 48 Wistar rats received glibenclamide (20 mg/kg/day, s.c.) and 24 h later, these animals, and an additional group of 45 rats, were injected with cisplatin (5 mg/kg, i.p.). In addition, 38 control rats were injected with saline, i.p. Twenty-four hours and 5 days after saline or cisplatin injections blood and urine samples were collected to evaluate renal function and the kidneys were removed for analysis of neutrophil accumulation, tumor necrosis factor-alpha and interleukin-1beta and histological and immunohistochemical studies. RESULTS: Cisplatin injection induced neutrophil recruitment and increased tumor necrosis factor-alpha and interleukin-1beta contents in renal cortices and outer medullae tissues. Cisplatin-treated rats also presented reduction in the glomerular filtration rate, as well as greater immunostaining for ED1 (macrophages/monocytes) and acute tubular necrosis. All of these alterations were reduced by treatment with glibenclamide. These effects seem to be related, at least in part, to the restriction of neutrophil recruitment and inflammatory process observed in the kidneys from glibenclamide+cisplatin-treated rats.

Role of myofibroblasts, macrophages, transforming growth factor-beta endothelin, angiotensin-II, and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin.

BACKGROUND: Animal models of aminoglycoside nephrotoxicity can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of fibronectin, alpha-smooth muscle actin (alpha-SM-actin), macrophages, endothelin,transforming growth factor-beta (TGF-beta) and angiotensin II (AII) in the renal cortex of rats, 5 and 30 days after stopping treatment with gentamicin, and the relationships with the histological features and renal function of these animals. METHODS: Forty-five female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, and 11 controls were injected with 0.15 M NaCl solution. The animals were killed 5 or 30 days after these injections and the kidneys removed for histological examination, enzyme immunoassay and immunohistochemical studies. The histological and immunohistochemical results were evaluated by scores reflecting the extent of lesion or staining. The percentage of tubulointerstitial lesions was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. The immunohistochemical studies showed increased fibronectin, alpha-SM-actin, ED-1, endothelin, TGF-beta and AII staining in the renal cortex from rats 5 and 30 days after gentamicin compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis and increased TGF-beta content in the renal cortex (p < 0.001), despite the recovery of renal function. The proportion of damaged areas was 23.17% +/- 5.23 in the renal cortex of these animals. CONCLUSIONS: Macrophages, myofibroblasts, TGF-beta, endothelin and AII may have contributed to the development of renal fibrosis in these rats.

Long-term evolution of the acute tubular necrosis (ATN) induced by glycerol: role of myofibroblasts and macrophages.

Late structural changes such as interstitial fibrosis in the renal cortex and tubular atrophy have been detected after severe acute tubular necrosis (ATN). The aim of this study was to investigate the expression of fibronectin, alpha-smooth muscle actin and macrophages during the evolution of the ATN induced by glycerol and their relationship with the late structural changes observed in the kidneys of these animals. Forty-nine male Wistar rats were injected with a 50% glycerol solution, 8 mL/kg (4 mL/kg applied i.m. to each hind leg) and 14 with 0.15 m NaCl solution. Before glycerol injection on day 1, water was removed for 17 h. Blood and urine samples were collected 1 day after the injection to quantify sodium and creatinine. The animals were killed 5, 30 and 60 days after the injections and the kidneys removed for histological and immunohistochemical studies. The results of the histological and immunohistochemical studies were scored according to the extent of lesion or staining in the cortical tubulointerstitium, respectively. The percentage of tubulointerstitial lesions was determined by morphometry. Glycerol-injected rats presented a transitory increase in plasma creatinine levels and in fractional sodium excretion. The immunohistochemical studies showed increased fibronectin, alpha-smooth muscle actin (alpha-SM-actin), TGF-beta and ED-1 (macrophages) staining in the renal cortex from rats killed 5, 30 and 60 days after glycerol injection (P < 0.05) compared to control. The animals killed on day 30 and 60 also presented chronic lesions (fibrosis, tubular dilatation and atrophy) in the renal cortex, despite the recovery of renal function. Macrophages, TGF-beta and myofibroblasts may have contributed to the development of renal fibrosis in these rats.