MK-886 attenuates kidney injury induced after trauma/shock by preventing flap and 5-lo interactions in kidney tubules

Acute kidney injury (AKI), a clinical syndrome, is a sudden onset of kidney failure that severely affects the kidney tubules. One potential treatment is dexmedetomidine (DEX), a highly selective α2-adrenoreceptor agonist that is used as an anesthetic adjuvant. It also has anti-inflammatory, neuroprotective, and sympatholytic qualities. The aim of this study was to establish whether DEX also offers protection against ischemia and reperfusion- (I/R-) induced AKI in rats. An intraperitoneal injection of DEX (25 μg/kg) was administered 30 min prior to the induction of I/R. The results indicate that in the I/R rats, DEX played a protective role by reducing the damage to the tubules and maintaining renal function. Furthermore, in response to I/R, the DEX treatment reduced the mRNA expression of TNF-α, IL-1β, IL-6, and MCP-1 in the kidney tissues and the serum levels of TNF-α, IL-1β, IL-6, and MCP-1. DEX also reduced the levels of oxidative stress and apoptosis in the tubular cells. These results indicate that in response to I/R kidney injury, DEX plays a protective role by inhibiting inflammation and tubular cell apoptosis, reducing the production of reactive oxygen species, and promoting renal function.

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Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16245030 ◽

2019 ◽

Vol 16 (24) ◽

pp. 5030 ◽

Cited By ~ 11

Author(s):

Xiping Yi ◽

Shuaishuai Xu ◽

Feiyu Huang ◽

Cong Wen ◽

Shuilin Zheng ◽

...

Keyword(s):

Chronic Exposure ◽

Kidney Injury ◽

Oral Exposure ◽

Control Group ◽

Interstitial Tissue ◽

Kidney Tubules ◽

Potential Influence ◽

First Time ◽

Histopathological Investigation

Microcystin-LR (MC-LR) is a potent hepatotoxin, but a few studies suggested that it might also induce nephrotoxicity. However, nephrotoxicity induced by prolonged oral exposure to MC-LR is unknown. The aim of this study was to evaluate the potential influence of MC-LR on the kidney in mice following chronic exposure to MC-LR. In this study, we evaluated the nephrotoxicity of MC-LR in mice drinking water at different concentrations (1, 30, 60, 90, and 120 μg/L) for 6 months for the first time. The results showed that the kidney weights and the kidney indexes of mice were not altered in the MC-LR treated mice, compared with the control group. In addition, the renal function indicators revealed that the serum creatinine (SCr) levels were not significant changes after exposure to MC-LR. The blood urea nitrogen (BUN) levels were markedly decreased after exposure to 90 and 120 μg/L MC-LR for 3 months. The BUN levels were lower than that of the control group after exposure to 120 μg/L MC-LR for 6 months. The histopathological investigation revealed enlarged renal corpuscles, widened of kidney tubules, and lymphocyte infiltration in the interstitial tissue and the renal pelvis after exposure to 60, 90, and 120 μg/L MC-LR. Consequently, our results suggested that long-term exposure to MC-LR might be one important risk of kidney injury, which will provide important clues for the prevention of renal impairment.

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Villin and actin in the mouse kidney brush-border membrane bind to and are degraded by meprins, an interaction that contributes to injury in ischemia-reperfusion

AJP Renal Physiology ◽

10.1152/ajprenal.00703.2010 ◽

2011 ◽

Vol 301 (4) ◽

pp. F871-F882 ◽

Cited By ~ 21

Author(s):

Elimelda Moige Ongeri ◽

Odinaka Anyanwu ◽

W. Brian Reeves ◽

Judith S. Bond

Keyword(s):

Brush Border ◽

Knockout Mice ◽

Brush Border Membrane ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Mouse Kidney ◽

Cytoskeletal Proteins ◽

Kidney Tubules ◽

Wild Type

Meprins, metalloproteinases abundantly expressed in the brush-border membranes (BBMs) of rodent proximal kidney tubules, have been implicated in the pathology of renal injury induced by ischemia-reperfusion (IR). Disruption of the meprin β gene and actinonin, a meprin inhibitor, both decrease kidney injury resulting from IR. To date, the in vivo kidney substrates for meprins are unknown. The studies herein implicate villin and actin as meprin substrates. Villin and actin bind to the cytoplasmic tail of meprin β, and both meprin A and B are capable of degrading villin and actin present in kidney proteins as well as purified recombinant forms of these proteins. The products resulting from degradation of villin and actin were unique to each meprin isoform. The meprin B cleavage site in villin was Glu744-Val745. Recombinant forms of rat meprin B and homomeric mouse meprin A had Km values for villin and actin of ∼1 μM (0.6–1.2 μM). The kcat values varied substantially (0.6–128 s−1), resulting in different efficiencies for cleavage, with meprin B having the highest kcat/ Km values (128 M−1·s−1 × 106). Following IR, meprins and villin redistributed from the BBM to the cytosol. A 37-kDa actin fragment was detected in protein fractions from wild-type, but not in comparable preparations from meprin knockout mice. The levels of the 37-kDa actin fragment were significantly higher in kidneys subjected to IR. The data establish that meprins interact with and cleave villin and actin, and these cytoskeletal proteins are substrates for meprins.

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Mycotoxic porcine nephropathy and spontaneous occurrence of ochratoxin A residues in kidneys of slaughtered swine

Zbornik Matice srpske za prirodne nauke ◽

10.2298/zmspn0916081m ◽

2009 ◽

pp. 81-90 ◽

Cited By ~ 1

Author(s):

Dragan Milicevic ◽

Verica Juric ◽

Aleksandra Dakovic ◽

Miljan Jovanovic ◽

Srdjan Stefanovic ◽

...

Keyword(s):

Ochratoxin A ◽

Histopathological Examination ◽

Kidney Injury ◽

Kidney Tubules ◽

Cell Vacuolization ◽

Spontaneous Occurrence ◽

Slaughtered Pigs

In order to find information on the occurrence of mycotoxic porcine nephropathy in Serbia, during a six month period (2006/2007) samples of kidney from individual healthy slaughtered pigs were collected (n=90) and analyzed by HPLC for ochratoxin A. In addition, histological examinations were carried out. The incidence of OTA in kidney was 33,3% and varied between 0.17-52.5 ng/g. Histopathological examination of kidneys confirmed tubulopathies with oedema and cell vacuolization. In addition, hemorrhages and necrosis of proximal kidney tubules cells were found. These findings indicate that it is likely that most of the kidney injury is related to ochratoxin A and other nephrotoxic compounds which enhance the toxicity of OTA.

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Occurrence of ochratoxin A and heavy metals in tissues associated with porcine nephropathy in Serbia

World Mycotoxin Journal ◽

10.3920/wmj2008.1074 ◽

2009 ◽

Vol 2 (3) ◽

pp. 347-356

Author(s):

D. Milićević ◽

V. Jurić ◽

S. Stefanović ◽

M. Jovanović ◽

Z. Petrović ◽

...

Keyword(s):

Heavy Metals ◽

Ochratoxin A ◽

Histopathological Examination ◽

Kidney Injury ◽

Kidney Tubules ◽

Cadmium Lead ◽

Slaughtered Pigs

In order to find information on the occurrence of mycotoxic porcine nephropathy in Serbia, during a six month period (2006/2007) samples of blood, kidney and liver from individual animals were collected from healthy slaughtered pigs (n=90) and analysed by HPLC for ochratoxin A (OTA). In addition, the presence of nephrotoxic heavy metals such as cadmium, lead, mercury and arsenic were measured and the kidneys pathohistologically examined. Of the 90 liver samples, 26.6% contained OTA in the range of 0.22-14.5 ng/g. The incidence of OTA in serum and kidney were very similar (30 and 31.1%), but varied between 0.24-220.8 ng/ml and 0.17-52.5 ng/g, respectively. The presence of mercury was confirmed in 33.3% of kidney samples and concentrations ranged between 0.005-0.055 mg/kg, while cadmium was found less frequently (27.7% positive samples) but at higher levels (0.05-1.23 mg/kg). The presence of arsenic was found in only one sample, while lead was not detected in any sample. Histopathological examination of kidneys confirmed tubulopathies with oedema and cell vacuolisation. In addition, haemorrhages and necrosis of proximal kidney tubules' cells were found. These findings indicate that it is likely that most of the kidney injury is related to OTA and other nephrotoxic compounds which enhance the toxicity of OTA.

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