Glucose Alters the Susceptibility of Mesangial Cells to Contrast Media

Wasaki, Masahiko; Sugimoto, Jiro; Shirota, Kinji

doi:10.1097/00004424-200107000-00001

Cited by 23 publications

(21 citation statements)

References 33 publications

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“…Given all that, ERK1/2 and JNK expression might be involved in iodinated contrast media-induced renal cell apoptosis in diabetic rats. Based on the findings of our study and others, 11,12,[15][16][17][26][27][28][29] we propose a pathophysiologic mechanism for apoptosis induced by ionic HOCM in diabetic rats (Figure 4). According to these findings, ERK1/2 and JNK pathway may be a target for novel therapeutic intervention in CIAKI.…”

Section: Discussionsupporting

confidence: 75%

“…Therefore, the hyperglycemia itself makes the kidney more susceptible to CIAKI. 22 Several in vitro studies also 11,12 demonstrated that high-glucose condition enhanced the susceptibility of renal cells to the cytotoxic effects (apoptosis) of both the HOCM and LOCM. In other words, the combination of high-glucose and contrast media has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of CIAKI.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the combination of these effects had a synergistic effect on accentuating renal tubular apoptosis and therefore, it increased the risk of CIAKI. 11,12 Different extracellular stimuli induces activation of multiple members of the mitogen activated protein kinases (MAPK) including c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), extracellular signal-regulated kinase1/2 (ERK1/2), p38 kinase, and the phosphoinositide 3-kinase (PI3K)/Akt pathway. [13][14][15] Lee et al 16,17 demonstrated that contrast media can activate the JNK/ATF2 pathway which plays a pivotal role in contrast media-induced cytotoxicity (apoptosis) in both in vitro and in vivo experiments.…”

Section: Introductionmentioning

confidence: 99%

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Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Jiao

Liu

et al. 2015

Renal Failure

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Background: The risk of contrast-induced acute kidney injury (CIAKI) is significantly increased in patients with diabetes mellitus. This study aimed to investigate molecular mechanisms of contrast media-induced apoptosis in diabetic rat kidneys, especially the involvement of ERK1/2 and JNK signal pathways. Methods: Diabetic Sprague-Dawley rats were induced by intraperitoneal injection of streptozotocin. Ten weeks later the normal and diabetic rats were administered high-osmolar contrast media (HOCM; meglumine diatrizoate) or normal saline (10 mL/kg) injection for 2 consecutive days. At 24 h after the operation, the rats were sacrificed, the blood samples were collected for examining serum creatinine and the kidneys were collected for determining the expression of caspase-3 by immunohistochemistry and the expression of Bcl-2, Bax, upstream signal molecule p-JNK, and p-ERK1/2 by western blotting. Results: The serum creatinine was significantly increased in diabetes + contrast media group (DC group) after operation compared with in the diabetic group (D group; 103.89 ± 9.01 mmol/L vs. 71.52 ± 7.03 mmol/L, p50.05). While creatinine clearance rate (Ccr) was significantly decreased in DC group after operation (1.49 ± 0.33 mL/min vs. 2.60 ± 0.54 mL/min, p50.05). Especially, in the diabetic kidney, the expression of caspase-3 was also significantly increased after intravenous injection of HOCM compared with normal saline. The expression level of upstream signal molecule p-JNK protein was apparently increased, but p-ERK1/2 protein was significantly decreased (both p50.05). Conclusions: The ionic HOCM-induced renal cells apoptosis in diabetic rats through activating the caspase-3 apoptotic pathway, which might be mediated by upstream MAPK (inhibiting p-ERK1/2 expression and promoting p-JNK expression) signal pathways.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Jiao

Liu

et al. 2015

Renal Failure

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“…(D) (C) studies, 21,22 and also on the fact that ICM are concentrated in the kidneys compared with blood plasma. Urinary concentrations of ICM can be up to 50-100 times that in plasma.…”

Section: Discussionmentioning

confidence: 99%

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

et al. 2011

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Nephrotoxicity, associated with the administration of iodinated X-ray contrast media (ICM), continues to be a major side effect in a significant number of vulnerable patients undergoing diagnostic X-ray imaging procedures. The molecular mechanisms underlying these adverse effects on the kidneys are unclear despite several decades of investigation. Side effects are more common after exposure to high-osmolar compared with low-osmolar ICM, suggesting that osmolality may be an important physical-chemical property related to nephrotoxicity. This investigation in cultured NRK 52-E cells, a cell line of renal origin, compares the in vitro toxicity of the iso-osmolal ICM iodixanol with the lowosmolal ICM iohexol, iopromide, and ioversol. The cellular toxicity was evaluated with the trypan blue exclusion assay, the MTT assay, and incidences of cell death. A qualitative assessment of vacuolation of the cultured NRK 52-E cells was taken as a measure of intracellular uptake of ICM. A difference in cell death incidence was observed between the iso-osmolal iodixanol and the low-osmolal iohexol, iopromide, and ioversol contrast media, with the isoosmolal iodixanol having the least effect in each of the in vitro systems tested. The osmolality of the contrast media appeared to be the major cause for the observed in vitro toxicity.

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“…Some studies suggest the generation of ROS as an important mechanism of direct RAs cytotoxicities. [7,8] The recommended clinical procedure used to reduce RA-induced damage to the kidneys is hydrating the patient before the administration of the RAs. [9][10][11][12] Recently, N-acetyl-cysteine, an antioxidant agent, has been used for RAs nephrotoxicities preventions.…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Independent Cytotoxicity Induced by Radiocontrast Agents in Tubular Cells (LLC-PK1 and MDCK)

et al. 2007

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Purpose. Radiocontrast agents (RAs) cause renal tubular damage by hemodynamic imbalance, which could cause hypoxic stimulus and direct cytotoxicity. However, reactive oxygen species (ROS) could be an important factor in RAs' direct cytotoxicity. This study investigated the involvement of ROS in deleterious effects produced by RAs on normoxic and hypoxic renal tubular cells. Materials and Methods. LLC-PK1 and MDCK were exposed to diatrizoate and ioxaglate in normoxic and hypoxic conditions. Apoptotic and necrotic cell death were assessed by acridine orange/ethidium bromide and annexin V methods. Hydrogen peroxide, superoxide anion, and malondialdehyde levels were analyzed by, respectively, 2′,7′-dichlorofluorescein, luminal, and thiobarbituric acid. Antioxidant agents were used to prevent cellular RAs damage. Results. Diatrizoate and ioxaglate decreased cellular viability in both cells, and this effect was enhanced by hypoxic conditions. Diatrizoate induced more injury than ioxaglate to both cell lines. LLC-PK1 underwent necrosis, while MDCK cells underwent apoptosis when exposed to diatrizoate. These results could not be attributed to an increase in osmolality. RAs did not increase hydrogen peroxide, superoxide anion or malondialdehyde levels in both cells. Additionally, N-acetyl-L-cysteine (NAC), ascorbic acid, α-tocopherol, glutathione, β-carotene, allopurinol, cimetidine, and citric acid did not protect cells against RAs damage. Surprising, NAC increased the cellular damage induced by ioxaglate in the both cell lines. Conclusion. The present study shows that RAs induce damage in cultured tubular cells, especially in hypoxic conditions. ROS were not involved in the observed RAs' cytotoxicity, and NAC increased ioxaglate-induced tubular damage.

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Glucose Alters the Susceptibility of Mesangial Cells to Contrast Media

Cited by 23 publications

References 33 publications

Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

Role of ERK1/2 and JNK phosphorylation in iodine contrast agent-induced apoptosis in diabetic rat kidneys

The Effects of the Iodinated X-Ray Contrast Media Iodixanol, Iohexol, Iopromide, and Ioversol on the Rat Kidney Epithelial Cell Line NRK 52-E

Reactive Oxygen Species Independent Cytotoxicity Induced by Radiocontrast Agents in Tubular Cells (LLC-PK1 and MDCK)

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