Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway

Su, Jinzi; Zou, Wei; Cai, Wenqin; Chen, Xiuping; Wang, Fangbing; Li, Shuizhu; Ma, Wenwen; Cao, Yangming

doi:10.1016/j.ejphar.2013.10.025

Cited by 29 publications

(28 citation statements)

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“…Statins reduce the levels of intracellular pro-inflammatory factors in several cellular systems by acting on the inhibition of producing enzymes (12,21,22). In the rat model used in the present study, pretreatment with atorvastatin reduced the iopamidol-induced release of TNF-α, IL-1β and IL-6, and improved renal function, including the levels of SCr, urine microprotein and uKIM-1.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

Yang

Liu

et al. 2017

Molecular Medicine Reports

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Contrast-induced nephropathy (CIN) is an iatrogenic acute renal failure occurring following the intravascular injection of iodinated radiographic contrast medium. However, the regulatory mechanisms for CIN remain to be fully elucidated. The present study aimed to investigate whether atorvastatin protects against CIN via anti-apoptotic effects by the upregulation of Hsp27 in vivo and in vitro. To determine whether atorvastatin attenuated CIN, the inflammatory response and apoptosis in vivo and in vitro, a rat model of iopamidol-induced CIN was used, and human embryonic proximal tubule (HK2) cell damage was assessed. The rats were assigned into four groups (n=10 per group), as follows: Control rats; rats+atorvastatin; rats + iopamidol; rats+iopamidol+atorvastatin. In vitro, the HK2 cells were treated with iopamidol in the presence or absence of atorvastatin, heat shock protein (Hsp)27 small interfering (si)RNA or pcDNA3.1-Hsp27. The renal tissues were examined histopathologically and collected for western blot analysis. The results showed that atorvastatin ameliorated the apoptosis and deterioration of renal function (P<0.05). Furthermore, atorvastatin reduced the iopamidol-induced activity of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/caspase-3 and increased the expression of Bcl-2 in vivo and in vitro. Notably, following treatment with Hsp27 siRNA or pcDNA3.1-Hsp27, it was found that iopamidol enhanced or weakened the upregulation of Bax/caspase-3 and downregulation of Bcl-2 in the HK2 cells, respectively. The results of the present study suggested that atorvastatin protected against contrast-induced renal tubular cell apoptosis through the upregulation of Hsp27 in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

Yang

Liu

et al. 2017

Molecular Medicine Reports

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“…RCM injection is also used to model CI-AKI [82, 84, 85, 175]. For example, RCM induces tubular necrosis in diabetic nephropathy kidneys (Figures 4(l) and 4(m)) [37]. A yes-or-no phenomenon regarding RCM dose has been reported in the diabetic CI-AKI model as 8 mL/kg or 10 mL/kg iopromide did not but 12 or 16 mL/kg did induce renal functional decline [9, 37].…”

Section: Further Histological Changes Related Primarily To the Modmentioning

confidence: 99%

“…(l) Tubular vacuolar degeneration (arrows), necrosis, hyaline casts (filled triangles), and cellular casts (hollow triangles) and inflammatory infiltration in contrast-treated diabetic and (m) normal rat kidney medulla (HE, 200x). From [37] with permission. Scale bar represents 100 μ m.…”

Section: Figurementioning

confidence: 99%

Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

Kiss

Hamar

2016

BioMed Research International

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Contrast-induced acute kidney injury (CI-AKI) can occur in 3–25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments.

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“…Such agents include cyclosporine, glycerol, cisplatin, and adriamycin (44)(45)(46). Su et al assessed the effect of contrast on artificially induced diabetic rats following streptozotocin therapy (47). It should be noted that the nephrotoxic effects of these agents may not be similar to human risk factors and may interfere with results.…”

Section: Pre-test Conditionsmentioning

confidence: 99%

“…Several series determined the degree of apoptosis using a TUNEL assay, for example the ApopTag Plus Peroxidase In Situ Apoptosis Detection Kit. This assay is performed on frozen sections of the renal parenchyma and allows the measurement of DNA fragmentation by labelling the newly formed 3'-OH groups with digoxigenin-nucleotides, which are then detected with a specific antibody (41,43,47,55,60,73). The specimens are incubated with the TUNEL reaction mixture, and TUNEL-positive cells are counted under a fluorescence microscope for quantitative assessment.…”

Section: Assessment Of Oxidative Stressmentioning

confidence: 99%

Experimental rat models for contrast-induced nephropathy; a comprehensive review

et al. 2020

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Contrast-induced nephropathy (CIN) is an iatrogenic disease caused by the parenteral administration of iodinated contrast media (CM). A number of agents are currently being assessed to minimise or prevent CIN. Such agents are typically assessed using rat models. The aim of this study was to provide a comprehensive review of the rat models of CIN used in pre-clinical research. The MEDLINE, EMBASE, Web of Science and Cochrane databases were systematically searched. Articles reporting rat models of CIN were included for assessment. Study designs, contrast agents and outcome measures were assessed. Of the assessed studies, a majority report a requirement for pre-existing renal impairment prior to the administration of CM. Outcome measures are heterogenous between studies, but typically include assessment and quantification of serum biochemical markers, cellular oxidative stress and histopathological changes. The significant variation in methodology reported in the current literature highlights the lack of consensus. The use of a reliable pre-contrast insult appears critical to result in the development of contrast nephropathy. The use of acceptable outcome measures appears to include serum laboratory markers, quantification of reactive oxygen species (ROS) and objective histopathological outcomes. ABSTRACT Implication for health policy/practice/research/medical education:Contrast-induced nephropathy (CIN) is an iatrogenic disease caused by the parenteral administration of iodinated contrast media. A number of agents are currently being assessed to minimise or prevent CIN, of which initial assessment of these agents are typically assessed using rat models. We provide a comprehensive review outlining previously utilised rat models for the assessment of CIN. This paper is of benefit, as it highlights the different approaches to studying this model and provides a framework for future trials assessing novel agents. Please cite this paper as: Perera M, Ischia J, Bolton D, Shulkes A, Baldwin GS, Patel O. Experimental rat models for contrast-induced nephropathy; a comprehensive review. J Nephropathol. 2020;9(2):e12.

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Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway

Cited by 29 publications

References 50 publications

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

Experimental rat models for contrast-induced nephropathy; a comprehensive review

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