Ioxitalamate induces renal tubular apoptosis via activation of renal efferent nerve-mediated adrenergic signaling, renin activity, and reactive oxygen species production in rats

Shih Ping Hsu, Tun Jun Tsai, Chiang-Ting Chien

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Abstract

To investigate the unrecognized role of renal efferent nerve activity (RENA) in iodinated contrast media (CM)-induced acute kidney injury, we explored the effects of CM on RENA, renal hemodynamics, plasma renin activity (PRA), reactive oxygen species (ROS) production, and renal injury in rats. Four types of CM including ioxitalamate (high osmolar and ionic), ioxaglate (low osmolar and ionic), iohexol (low osmolar and nonionic), and iodixanol (iso-osmolar and nonionic) were given iv (1600 mg I/kg body weight) to urethane-anesthetized female Wistar rats. We measured RENA by electrophysiologic recording techniques, renal blood flow with Doppler ultrasound, PRA by radioimmunoassay, and ROS by an in vivo chemiluminescence method.We graded the severity of CM-induced vacuoles in cortical tubular cells stained by hematoxylin and eosin and apoptosis production in outer medulla by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Besides, the effects of pretreatment with iv β-adrenoceptor antagonist propranolol (10 mg/kg body weight), antioxidant N-acetylcysteine (100 mg/kg body weight), and renal denervation on CM-induced pathophysiologic parameters were determined. Ioxitalamate significantly increased RENA and renal vascular resistance, PRA, renal ROS production within 1 h, and formation of vacuoles and TUNEL apoptosis in renal tubular cells 2 h later; other CM had less effect on these parameters. On the other hand, propranolol, N-acetylcysteine, or renal denervation partially attenuated the ioxitalamate-aggravated responses on RENA, PRA, ROS production, and vacuole and TUNEL apoptosis formation in renal tubular cells. In conclusion, we suggest that ioxitalamate may induce acute tubular injury via aggravation of RENA, adrenergic signaling, PRA, and ROS production.

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalToxicological Sciences
Volume114
Issue number1
DOIs
Publication statusPublished - 2009 Nov 26

Fingerprint

Renin
Adrenergic Agents
Contrast Media
Rats
Reactive Oxygen Species
Chemical activation
Apoptosis
Kidney
Plasmas
Acetylcysteine
Propranolol
Ioxaglic Acid
In Situ Nick-End Labeling
Iohexol
Vacuoles
Chemiluminescence
DNA Nucleotidylexotransferase
Urethane
Hemodynamics
Hematoxylin

Keywords

  • Iodinated contrast media
  • N-acetylcysteine
  • Reactive oxygen species
  • Renal denervation
  • Renal nerve
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Toxicology

Cite this

@article{60b776eac25545458cf89c72ac0bd1d8,
title = "Ioxitalamate induces renal tubular apoptosis via activation of renal efferent nerve-mediated adrenergic signaling, renin activity, and reactive oxygen species production in rats",
abstract = "To investigate the unrecognized role of renal efferent nerve activity (RENA) in iodinated contrast media (CM)-induced acute kidney injury, we explored the effects of CM on RENA, renal hemodynamics, plasma renin activity (PRA), reactive oxygen species (ROS) production, and renal injury in rats. Four types of CM including ioxitalamate (high osmolar and ionic), ioxaglate (low osmolar and ionic), iohexol (low osmolar and nonionic), and iodixanol (iso-osmolar and nonionic) were given iv (1600 mg I/kg body weight) to urethane-anesthetized female Wistar rats. We measured RENA by electrophysiologic recording techniques, renal blood flow with Doppler ultrasound, PRA by radioimmunoassay, and ROS by an in vivo chemiluminescence method.We graded the severity of CM-induced vacuoles in cortical tubular cells stained by hematoxylin and eosin and apoptosis production in outer medulla by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Besides, the effects of pretreatment with iv β-adrenoceptor antagonist propranolol (10 mg/kg body weight), antioxidant N-acetylcysteine (100 mg/kg body weight), and renal denervation on CM-induced pathophysiologic parameters were determined. Ioxitalamate significantly increased RENA and renal vascular resistance, PRA, renal ROS production within 1 h, and formation of vacuoles and TUNEL apoptosis in renal tubular cells 2 h later; other CM had less effect on these parameters. On the other hand, propranolol, N-acetylcysteine, or renal denervation partially attenuated the ioxitalamate-aggravated responses on RENA, PRA, ROS production, and vacuole and TUNEL apoptosis formation in renal tubular cells. In conclusion, we suggest that ioxitalamate may induce acute tubular injury via aggravation of RENA, adrenergic signaling, PRA, and ROS production.",
keywords = "Iodinated contrast media, N-acetylcysteine, Reactive oxygen species, Renal denervation, Renal nerve, Renin-angiotensin system",
author = "Hsu, {Shih Ping} and Tsai, {Tun Jun} and Chiang-Ting Chien",
year = "2009",
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language = "English",
volume = "114",
pages = "149--158",
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TY - JOUR

T1 - Ioxitalamate induces renal tubular apoptosis via activation of renal efferent nerve-mediated adrenergic signaling, renin activity, and reactive oxygen species production in rats

AU - Hsu, Shih Ping

AU - Tsai, Tun Jun

AU - Chien, Chiang-Ting

PY - 2009/11/26

Y1 - 2009/11/26

N2 - To investigate the unrecognized role of renal efferent nerve activity (RENA) in iodinated contrast media (CM)-induced acute kidney injury, we explored the effects of CM on RENA, renal hemodynamics, plasma renin activity (PRA), reactive oxygen species (ROS) production, and renal injury in rats. Four types of CM including ioxitalamate (high osmolar and ionic), ioxaglate (low osmolar and ionic), iohexol (low osmolar and nonionic), and iodixanol (iso-osmolar and nonionic) were given iv (1600 mg I/kg body weight) to urethane-anesthetized female Wistar rats. We measured RENA by electrophysiologic recording techniques, renal blood flow with Doppler ultrasound, PRA by radioimmunoassay, and ROS by an in vivo chemiluminescence method.We graded the severity of CM-induced vacuoles in cortical tubular cells stained by hematoxylin and eosin and apoptosis production in outer medulla by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Besides, the effects of pretreatment with iv β-adrenoceptor antagonist propranolol (10 mg/kg body weight), antioxidant N-acetylcysteine (100 mg/kg body weight), and renal denervation on CM-induced pathophysiologic parameters were determined. Ioxitalamate significantly increased RENA and renal vascular resistance, PRA, renal ROS production within 1 h, and formation of vacuoles and TUNEL apoptosis in renal tubular cells 2 h later; other CM had less effect on these parameters. On the other hand, propranolol, N-acetylcysteine, or renal denervation partially attenuated the ioxitalamate-aggravated responses on RENA, PRA, ROS production, and vacuole and TUNEL apoptosis formation in renal tubular cells. In conclusion, we suggest that ioxitalamate may induce acute tubular injury via aggravation of RENA, adrenergic signaling, PRA, and ROS production.

AB - To investigate the unrecognized role of renal efferent nerve activity (RENA) in iodinated contrast media (CM)-induced acute kidney injury, we explored the effects of CM on RENA, renal hemodynamics, plasma renin activity (PRA), reactive oxygen species (ROS) production, and renal injury in rats. Four types of CM including ioxitalamate (high osmolar and ionic), ioxaglate (low osmolar and ionic), iohexol (low osmolar and nonionic), and iodixanol (iso-osmolar and nonionic) were given iv (1600 mg I/kg body weight) to urethane-anesthetized female Wistar rats. We measured RENA by electrophysiologic recording techniques, renal blood flow with Doppler ultrasound, PRA by radioimmunoassay, and ROS by an in vivo chemiluminescence method.We graded the severity of CM-induced vacuoles in cortical tubular cells stained by hematoxylin and eosin and apoptosis production in outer medulla by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Besides, the effects of pretreatment with iv β-adrenoceptor antagonist propranolol (10 mg/kg body weight), antioxidant N-acetylcysteine (100 mg/kg body weight), and renal denervation on CM-induced pathophysiologic parameters were determined. Ioxitalamate significantly increased RENA and renal vascular resistance, PRA, renal ROS production within 1 h, and formation of vacuoles and TUNEL apoptosis in renal tubular cells 2 h later; other CM had less effect on these parameters. On the other hand, propranolol, N-acetylcysteine, or renal denervation partially attenuated the ioxitalamate-aggravated responses on RENA, PRA, ROS production, and vacuole and TUNEL apoptosis formation in renal tubular cells. In conclusion, we suggest that ioxitalamate may induce acute tubular injury via aggravation of RENA, adrenergic signaling, PRA, and ROS production.

KW - Iodinated contrast media

KW - N-acetylcysteine

KW - Reactive oxygen species

KW - Renal denervation

KW - Renal nerve

KW - Renin-angiotensin system

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