Sesame oil prevents acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats.

The aim of the study was to investigate the effect of sesame oil on acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats. Acute kidney injury was induced by a 5-day course of daily gentamicin injections (100 mg/kg of body weight, subcutaneously) and then iodinated contrast (4 ml/kg, intravenously) in male specific-pathogen-free Sprague-Dawley rats. Sesame oil (0.5 ml/kg, orally) was given 1 h before iodinated contrast. Renal function and oxidative stress were assessed 6 h after iodinated contrast injection. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. Renal oxidative stress was assessed by determining renal lipid peroxidation, myeloperoxidase, hydroxyl radical, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase levels. Sesame oil significantly prevented the rise of serum blood urea nitrogen and creatinine levels. Furthermore, there was a parallel inhibition of the rise in levels of expression of renal lipid peroxidation, myeloperoxidase, hydroxyl radicals, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase in rats with gentamicin-plus-iodinated contrast-induced acute kidney injury. We conclude that sesame oil may attenuate aminoglycoside-plus-iodinated contrast-induced acute kidney injury by inhibiting renal oxidative stress in rats.

Hydration and N-acetylcysteine in acute renal failure caused by iodinated contrast medium: an experiment with rats.

BACKGROUND: The involvement of nephrotoxic agents in acute renal failure (ARF) has increased over the last few decades. Among the drugs associated with nephrotoxic ARF are the radiologic contrast media whose nephrotoxic effects have grown, following the increasing diagnostic use of these agents. METHODS: We evaluated the effect of iodinated contrast (IC) medium, administered in combination, or not, with hyperhydration or N-acetylcysteine (NAC), on creatinine clearance, production of urinary peroxides and renal histology of rats. Adult Wistar rats treated for 5 days were divided into the following groups: control (saline, 3 ml/kg/day, intraperitoneally [i.p.]), IC (sodium iothalamate meglumine, 3 ml/kg/day i.p.), IC + water (12 mL water, orally + IC, 3 ml/kg/day i.p. after 1 hour), IC + NAC (NAC, 150 mg/kg/day, orally + IC, 3 ml/kg/day i.p. after 1 hour) and IC + water + NAC. RESULTS: IC medium reduced renal function, with maintenance of urinary flow. Hyperhydration did not reduce the nephrotoxic effect of the IC agent, which was observed in the group IC + NAC. The combination of hyperhydration and NAC had no superior protective effect compared with NAC alone. An increase in urinary peroxides was observed in the IC group, with NAC or water or the combination of both reducing this parameter. Histopathologic analysis revealed no significant alterations. CONCLUSIONS: In summary, given 5 days previously, NAC was found to be more effective than hyperhydration alone in the prevention of contrast-induced acute renal failure.

A rat EEG model for evaluating contrast media neurotoxicity.

The electroencephalographic (EEG) effects of intracisternally administered x-ray contrast media were evaluated in rats as a means of assessing neurotoxicity. Rats were ventilated with a mixture of nitrous oxide and oxygen (70/30) sufficient to maintain light anesthesia/analgesia and neuromuscular blockade was induced to prevent movement artifacts. A femoral artery was catheterized for monitoring arterial blood pressure (BP), heart rate, blood gases, and pH. Four 22-gauge stainless steel needle electrodes were inserted underneath the scalp for recording EEG. Approximately 1 hour after the start of EEG recording, test agents were injected via the cisterna magna and rats were placed in a 20 degrees head-down position. EEG and BP were monitored continuously for up to 160 minutes postinjection. Blood gases and pH were monitored periodically. The effects of meglumine iothalamate (IOT), metrizamide (MET), iogulamide (IOG), and ioversol (IOV) were compared at dose levels from 30 to 240 mgI/kg. Normal saline was injected as a control substance and caused no changes in EEG, blood gases, pH, and BP for up to 160 minutes postinjection. IOT (30 mg I/kg) produced profound EEG effects consistent with epileptogenic activity, followed by slowing and subsequent death in 3 of 4 animals. Metrizamide had minimal EEG effects at 30 mg I/kg but at 60 mg I/kg, and 120 mg I/kg produced moderate to severe EEG changes including epileptiform patterns and death in 33% of animals. IOV caused mild EEG abnormalities in 4 of 12 animals at 120 mg I/kg, mild EEG abnormalities in 6 of 11 animals, and moderate EEG abnormalities in 1 of 11 animals at 240 mg I/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Cutaneous ulceration due to contrast extravasation. Experimental assessment of injury and potential antidotes.

Severe cutaneous ulceration may occur as a result of contrast media extravasation. We established a definitive animal model for assessing the cutaneous toxicity of commonly employed agents and used this model to evaluate possible antidotes to the effects of contrast media extravasation. The contrast agents studied were: meglumine/sodium diatrizoate 76%, meglumine iothalamate 60% and 43%, meglumine/sodium ioxaglate 60%, iohexol 350, and iopamidol 370, in varying volumes and osmolalities. Hypertonic saline (950 and 1900 mOsm/kg) also was injected. Agents were injected intradermally into BALB/c mice. The higher osmolality agents produced dose-dependent skin ulcerations. The lower osmolality agents failed to produce any skin lesions after the same volume doses. Hypertonic saline produced skin toxicity in a dose-dependent fashion similar to hyperosmolar contrast agents. Three antidotes were tested: hyaluronidase, topical heat, and topical cold. Hyaluronidase significantly reduced skin toxicity when injected immediately following contrast injection. Cold also significantly reduced skin toxicity, while heat caused no improvement.

Histologic effects of Amipaque (metrizamide) and various contrast media on mouse peritoneum.

The histologic effects of Amipaque and various commonly used contrast media on mouse peritoneum were studied by intraperitoneal injections of Amipaque 370 mg I/ml and 170 mg I/ml, Conray 300 mg I/ml, Conray Meglumine 282 mg I/ml, Urografin 60% and 76%, Gastrografin and barium sulfate. Amipaque and the other water-soluble media cause no deleterious effects, whereas barium sulfate evokes granulomatous inflammatory reaction. Amipaque is suitable for gastrointestinal studies when leakage into the peritoneal cavity is expected.

Pulmonary edema following high intravenous doses of ionic contrast media. Effect of the anion composition and concentration.

High intravenous doses of diatrizoate are known to induce a profound degree of pulmonary edema which is dose- and injection rate-dependent in the rat. In this study, meglumine salts of diatrizoate, iothalamate, and metrizoate were evaluated for their capacity to induce pulmonary edema following intravenous injections. Differences in anion composition or concentration of diatrizoate meglumine/sodium salts did not cause significantly different degrees of pulmonary edema.

Comparison of nonionic and ionic contrast agents in the rabbit lung.

The objective of this study was to determine the short- and long-term radiographic, physiologic and histologic changes elicited in the lung of rabbits following the aspiration of commonly used radiographic contrast agents. All agents used, including nonionic agents, caused radiographically evident pulmonary edema which cleared by 24 hours. The contrast materials with higher osmolality, viscosity, and iodine content elicited the greatest physiologic and pathologic changes. No differences were found between an ionic and a nonionic agent with similar viscosities and iodine content, despite a lower osmolality in the nonionic agent. No contrast agent is innocuous when introduced into the lung.

Adult peripheral angiography. Results from four North American randomized clinical trials of ionic media vs. iohexol.

Four, randomized, double blind comparisons of iohexol versus ionic media for peripheral angiography are summarized. Iohexol is safe, effective, and significantly less painful than ionic media for this indication.

Release of serotonin from human platelets in vitro by radiographic contrast media.

Both ionic and nonionic, monomeric and dimeric contrast media were found to release serotonin from intact human platelets in vitro. The monomeric contrast media were compared at the concentration range of 25 mg I/ml. Iothalamate was the strongest and the statistically equal metrizamide iopamidol, and P-297 were the weakest releasers. Monomeric and dimeric contrast media were compared at concentration ranges of 50 and 100 mg I/ml. They ranked, in descending order of serotonin releasing potency: iodipamide, iothalamate, P-127, iopamidol, and a statistically indistinguishable group of the monoacid dimer P-286, the nonionic dimer ZK 74 435, and metrizamide. The capability of contrast media to release serotonin seems to be a composite result of their specific physical and molecular structural properties.

Role of red blood cell deformation in toxicity of contrast media in cerebral angiography.

The authors investigated the effect on the brain of red blood cells that had been modified by contrast media. Rat blood was mixed with an equivolume of contrast media, and up to 200 microL of the mixture was infused to the internal carotid artery of the rat. Evans blue was administered intravenously to assess the integrity of the blood-brain barrier (BBB). Immediately after the death of the animal, or 2.5 hours after the infusion, the brain was removed for evaluation of the degree of BBB destruction and edema. Extensive destruction of the BBB, cerebral edema, and death of the animals were induced by infusion of blood mixed with an ionic contrast medium, such as diatrizoate and iothalamate, which deformed red blood cells. Microscopic observation showed atrophy and necrosis of nerve cells and decomposition of nerve fibers in the affected area of the brain. Cerebral damage was not observed in rats injected with blood mixed with a nonionic contrast medium such as iopamidol, iopromide, or metrizamide, which had less effect on red blood cells. Cerebral damage also was observed in the rats injected with blood mixed with a hyperosmotic solution of mannitol, as well as washed red blood cells mixed with an ionic contrast medium. This study's results indicate that hyperosmotic ionic contrast media affect red blood cells and cause disturbance in cerebral circulation.

Effects of radiographic contrast agents on spinal cord physiology.

Segmental reflexes in the spinal cords of cats anesthetized with chloralose were used to evaluate the neurophysiologic effects of radiographic contrast agents. The exposed lumbar spinal cord was bathed with concentrations of ionic and nonionic agents including saline, sodium meglumine diatrizoate, meglumine iothalamate, meglumine iocarmate, and metrizamide. The following responses were evaluated: flexor and extensor monosynaptic reflex; polysynaptic flexion reflexes; spontaneous ventral root activity. Hypertonic solutions generally produced a transient decrease in all reflex activity for up to 1 hour. Isotonic solutions produced no significant changes in the monosynaptic responses, but an increase in amplitude of polysynaptic responses, and increased spontaneous activity. The usual facilitory effects of flexion reflex on the flexor monosynaptic reflex were unchanged, but the expected inhibitory effect of flexion reflex on the extensor monosynaptic reflex was changed to excitatory. The relative ability to produced these effects was sodium meglumine diatrizoate greater than meglumine iothalamate greater than meglumine iocarmate greater than metrizamide.

Effect of meglumine iothalamate on renal hemodynamics and function in the diabetic rat.

Diabetic rats were given an intravenous (external jugular vein) injection of 3 mg/kg of 60% meglumine iothalamate to test for this contrast agent's functional effects on the kidney. Rats were made diabetic by the intravenous injection of 60 mg/kg streptozotocin six months prior to the experiment and received no treatment during the interim. Glomerular filtration rate, renal blood flow, blood pressure, and sodium reabsorption were measured immediately before and at timed intervals after the administration of the contrast agent. In the diabetic rats, meglumine iothalamate caused a small and brief increase in renal blood flow followed by a sustained decrease; in the control animals an initial rapid rise was followed by a sustained elevation. Glomerular filtration rate also decreased slightly after contrast agent injection and remained depressed below baseline in the diabetic rats, whereas in the control animals it rose slightly above baseline and returned to control values by the end of the experiment. Sodium reabsorption was initially much higher than that of the controls, and it remained much higher throughout the experiment but decreased slightly just after injection of the contrast agent. Volume expansion of the diabetic animals decreased fractional sodium reabsorption to levels similar to those of the control rats but did not normalize the response of renal blood flow, glomerular filtration rate, or sodium reabsorption. Dehydration of control animals increased initial sodium reabsorption to levels similar to those of the diabetic animals but did not normalize the response to the contrast agent of the glomerular filtration rate, renal blood flow, or sodium reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of renal hemodynamic and functional changes following intravascular contrast to the renin-angiotensin system and renal prostacyclin in the dog.

Deterioration in renal function has been observed after the use of intravascular contrast media. In an attempt to identify factors responsible for this phenomenon, meglumine iothalamate (Conray 60), in a dosage range of 2.5-3.3 ml/kg, was injected as a bolus into the aorta of dogs. Serial measurements were made of parameters of renal function as well as of changes in aortic and renal venous levels of angiotensin II, renin activity, and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin. The major findings were (1) an initial, brief increase followed by approximately a 20% sustained decrease in renal blood flow and creatinine clearance, (2) no significant changes in angiotensin II and renin levels, and (3) a significant decline in the renal secretory rate of 6-keto-PGF1 alpha. These observations suggest that the suppression of prostacyclin, rather than the activation of the renin-angiotensin system, may contribute to the renal function changes attending the use of intravascular contrast media.

Intrathecal tolerance of metrizamide in chloralose anesthetized cats.

The water soluble radiopaque medium, metrizamide (Amipaque) was introduced into the lumbar subarachnoid space in chloralose anesthetized cats at a standard volume of 0.35 cc/kg in concentrations of 300 mgI/cc to 500 mgI/cc during EMG recording. These animals did not differ from controls which received cerebrospinal fluid under otherwise identical conditions; both groups usually showed some mild and occasional muscle fasciculations or mild spasms. Treatment with metrizamide appeared to be a less deleterious procedure than that using hyperosmotic sucrose (1.32 M) as judged from EMG records. In contrast, equivalent amounts of neglumine iothalamate produced frank convulsions in 7 of 15 cases and a range of hyperirritability in the remaining 8.

Chemotoxicity of contrast media and clinical adverse effects: a review.

The clinical effects of contrast agents not only result from high osmolality, but also from their own specific pharmacology, which mediates chemotoxic effects. In this review, the chemotoxic effects of the new nonionic agent, iohexol, are compared with those of standard ionic and other low osmolality contrast agents, ionic and nonionic. Iohexol has the lowest chemotoxicity of any agent yet synthesized. Its low systemic toxicity is the combined result of low chemotoxicity and low osmolality. Mechanisms of severe adverse reactions are reviewed, including the views of Lasser and Lalli, and the view that emphasizes the importance of cardiotoxic and hemodynamic effects. It is concluded that whichever view is taken of the mechanisms of severe adverse reactions, the new nonionic agents are likely to be safer than the ionic agents now in use.

Clinical trial of Iohexol vs. Conray 60 for cerebral angiography.

Iohexol, a new nonionic contrast agent, and Conray 60 were compared in a double-blind clinical trial of 60 patients for safety, imaging effectiveness, and patient discomfort in cerebral angiography. There was no significant difference between the two agents in physiologic changes, film quality, or incidence of adverse effects in the 60 patients. One patient in the iohexol group suffered a cardiac arrest, which was clinically due to septic shock and was probably the result of inadvertent contamination of the iohexol used for test injections in this case. Bacterial growth can be supported in iohexol under certain circumstances, due to the lack of preservatives in this contrast material. The patients in the iohexol group experienced significantly less discomfort than the Conray 60 group. Iohexol is a safe, effective contrast agent when handled properly and causes less discomfort to patients than Conray 60.

A role for nitric oxide in X-ray contrast material toxicity.

RATIONALE AND OBJECTIVES: We assessed the role that nitric oxide (NO) plays in contrast media (CM) toxicity, using 100% lethal dose (LD100) studies in hyperimmune Brown Norway (BN) rats. METHODS: Ninety-two BN rats and 41 Sprague-Dawley (SD) rats underwent CM LD100 tail vein injections with methylglucamine iothalamate or sodium iothalamate to the point of cessation of respiration. Methylglucamine hydrochloride also was injected. The injections were accompanied by L-arginine (L-Arg) or D-arginine (D-Arg) analogues or by an H1 blocker. L-Arg analogues inhibit NO formation, and D-Arg analogues do not. RESULTS: An L-Arg analogue, but not a D-Arg analogue, increased the tolerance of BN rats (p < .005) for methylglucamine iothalamate but not for sodium iothalamate. The L-Arg analogue also protected BN rats against methylglucamine chloride injections (p < .002). H1 blockade protected BN rats against methylglucamine iothalamate (p < .0005) and methylglucamine chloride (p < .005) injections. None of these measures altered the CM tolerance of SD rats. In SD rats, injections of either methylglucamine iothalamate or sodium iothalamate along with a D-Arg analogue or normal saline were better tolerated than similar injections in BN rats (p < .01 and .002 for methylglucamine iothalamate and sodium iothalamate, respectively). In SD rats but not BN rats, sodium iothalamate was better tolerated than was methylglucamine iothalamate (p < .0005). CONCLUSION: NO appears to play a significant role in BN rats LD100 CM toxicity and has been implicated by others in the blood pressure fall characterizing some forms of antigen-induced anaphylaxis [1, 2]. The results of the current study and the literature suggest that methylglucamine-modulated release of histamine from mast cells may underlie the NO production.

An experimental study of different contrast media in the epidural space.

In the experimental study of different contrast media, metrizamide has been found to be very safe for epidurography as no clinical, radiologic, or histologic changes after epidural injection were seen. Next in order was meglumine iothalmate. However, sodium containing salts like sodium acetrazoate and sodium iothalmate were found to be very irritating to the nerve roots and the spinal cord and, therefore, should not be used for epidurographic studies.

A clinical and experimental study of meglumine iocarmate in the subarachnoid space: a complication of positive contrast ventriculography.

Meglumine iocarmate (Dimer-X) may be accidentally put into the subarachnoid space because of suboptimal technique during ventriculography. This may cause status epilepticus. Two cases of this complication are reported. It is emphasized that this should be avoided. Treatment is mentioned briefly.

Effects of sterilized micropulverized barium sulfate suspension and meglumine iothalamate solution on the genitourinary tract of healthy male dogs after retrograde urethrocystography.

A sufficient quantity of 30% w/v sterile barium sulfate suspension was infused into the caudal portions of urinary tracts of 12 young adult healthy male Beagles to induce vesicoureteral reflux. A control group of dogs was infused with a 7.5% solution of meglumine iothalamate. The dogs were radiographed at 1, 6, 13, and 29 days later. Three dogs from each group were euthanatized and necropsied (1 each) after radiography at each of these times. In some dogs, radiopacity in the prostate, urinary bladder, and renal pelvic diverticula due to barium persisted throughout the 30-day observation period. Opacity at or beyond 24 hours was not found in dogs infused with iothalamate. Light microscopy revealed barium either free or within macrophages in the submucosa of the bladder, in glandular and stromal areas of the prostate, and in the kidney. Renal barium was limited to pelvic diverticula (3 dogs), in a medullary tubule (1 dog), and in cortical tubules (2 dogs). Significant lesions attributable to barium were not seen in kidneys of dogs in the barium group. Iothalamate induced focal to multifocal inflammatory responses in some prostates; barium was phagocytosed by macrophages. Focal transient inflammatory and ulcerative lesions induced by bladder distention were observed in the bladder and urethral mucosa in both groups.