NTA and Fe(III)NTA: differential patterns of renal toxicity in subchronic studies

2002 ◽  
Vol 21 (8) ◽  
pp. 445-452 ◽  
Author(s):  
E Leibold ◽  
K Deckardt ◽  
W Mellert ◽  
B Potthoff-Karl ◽  
O Grundler ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Lipid Peroxidation ◽  
Low Dose ◽  
Renal Toxicity ◽  
Intraperitoneal Administration ◽  
Nitrilotriacetic Acid ◽  
Cell Cytotoxicity ◽  
Thermodynamic Consideration ◽  
Kidney Toxicity ◽  
Kidney Homogenate

Differential patterns in terms of nephropathology and 8-hydroxyguanine formation in the course of oral 28-day studies were observed with nitrilotriacetic acid (NTA) and FeNTA. FeNTA, but not NTA, caused enhanced 8-hydroxyguanine formation in kidney DNA after oral and intraperitoneal administration. Enhanced lipid peroxidation in the kidney homogenate was observed with FeNTA as well as with NTA. For NTA, the low dose (9 mg/kg per day) was without adverse effect. The kidney toxicity of oral FeNTA (50, 200, and 1000 mg/ kg per day) was only mild, 50 mg/ kg per day; however, it still led to an increased 8-hydroxyguanine content. The relevance of Iron(III) (Fe(III)) or Fe(III)NTA formation as a relevant mediator of NTA-related toxicity was excluded on the basis of these data. Also, a thermodynamic consideration presented here, supports the view that zinc (Zn), and not Fe, is likely to mediate the tubular cell cytotoxicity of NTA.

Nigella sativa Seed Protects Against Cadmium-induced Renal Toxicity in Rats

2020 ◽  
Vol 14 (2) ◽  
pp. 140-149
Author(s):  
Ikenna Kingsley Uchendu ◽  
Henshaw Uchechi Okoroiwu
Keyword(s):  
Low Dose ◽  
Renal Toxicity ◽  
Histopathological Examination ◽  
Nigella Sativa ◽  
Intraperitoneal Administration ◽  
Albino Rats ◽  
High Dose ◽  
Protective Effects ◽  
Oral Group ◽  
Nigella Sativa Seed

Background: Prevalence of chemical-induced renal injuries has been on a fast rise over the years and has become the leading cause of mortality and morbidity in the society, with environmental pollutants, heavy metals inclusive, seen as the causal agents. Recently, the role of medicinal foods in human health has gained considerable attention. Objective: We investigated the protective effects of methanolic extract of Nigella sativa (MENS) (Black seed) against cadmium-induced renal toxicity in albino rats. Methods: Twenty-five (25) male albino rats, weighing (150-170g), were randomly grouped into five groups: A-E. Group B (Negative Control) received intraperitoneal administration of cadmium chloride (CdCl2, 5mg/kg) only, group C received CdCl2 and low dose MENS (300mg/kg, oral), group D received CdCl2 and high dose MENS (600mg/kg, oral), group E (Positive control) received CdCl2 and Vitamin C (200mg/kg, oral), for 7 days. No treatment was administered to group A (Normal control). Renal injury was assessed by measuring serum levels of Na+, K+, creatinine and blood urea nitrogen (BUN) using standard methods. The kidneys were harvested for histopathological examination. Results: CdCl2 induced significant nephrotoxicity with marked elevation in the levels of biochemical markers of renal functions (p<0.05 or p<0.01); these were, however, ameliorated by a low dose of MENS. Histopathological examination of the kidney sections supported the biochemical findings. Conclusion: We conclude that Nigella sativa seed extract, at a low dose, is potentially nephroprotective against harmful chemical toxins such as cadmium.

Abstract 528: Dose- And Salt-dependency Of Angiogenesis Inhibition-induced Blood Pressure Rise And Renal Toxicity

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Stephanie Lankhorst ◽  
Mariëtte H Kappers ◽  
Stefan Sleijfer ◽  
A H Danser ◽  
Anton H van den Meiracker
Keyword(s):  
Low Dose ◽  
Renal Toxicity ◽  
Pressure Rise ◽  
High Salt ◽  
High Dose ◽  
Low Doses ◽  
High Salt Diet ◽  
Salt Diet ◽  
Angiogenesis Inhibition ◽  
Cystatine C

Angiogenesis inhibition with the VEGF inhibitor sunitinib is an established anti-cancer therapy, inducing hypertension and nephrotoxicity. We explored the dose- and salt-dependency of these side effects. In male WKY rats, mean arterial pressure (MAP) was monitored telemetrically during oral treatment with a high (27.5 mg/kg.day, n=14), an intermediate (14 mg/kg.day, n=6) and low dose (7 mg/kg.day, n=6) of sunitinib or vehicle (n=8) after normal salt diet for 2 weeks. The low dose-model was also combined with a high salt diet (8% NaCl and saline water). Eight days after administration rats were sacrificed and blood and 24h urine samples collected for biochemical measurements. With the high dose of sunitinib, MAP increased from 94.7±0.9 mmHg to 125.8±1.5 mmHg (Δ31.1±0.9 mmHg, p<0.001). The intermediate and low doses induced MAP rises of 24.3±2.7 mmHg (p<0.001) and 13.4±3.3 mmHg (p<0.001), respectively. The low dose of sunitinib with high salt, induced a MAP rise of 43.5±2.2 mmHg (p<0.001 compared to normal salt). With the high dose, circulating ET-1 increased from 0.6±0.1 pg/ml to 1.6±0.2 pg/ml (p<0.01) and serum cystatine-C from 4.5±0.1 mg/L to 6.6±0.3 mg/L (p<0.001). Comparable increases in circulating ET-1 were seen with the intermediate and low doses, whereas serum cystatine-C did increase with the intermediate dose (to 6.3±0.1 mg/L, p0.05). Serum cystatine-C levels with low and high salt were identical. With the high dose of sunitinib, proteinuria increased from 7.5±1.3 to 33.3±4.8 mg/day (p<0.05). The rise in proteinuria was attenuated with the intermediate (16.2±2.1 mg/day, p<0.01) and low dose (19.9±3.3 mg/day, p<0.01), but increased to 40.4±30.1 mg/day (p>0.05) with high salt. Angiogenesis inhibition-induced hypertension and nephrotoxicity are dose-dependent with a lower threshold for the rise in BP than for renal toxicity. The BP rise observed with the low dose of sunitinib observed in normotensive rats is comparable to the sunitinib-induced BP rise observed in patients and clearly is salt-sensitive. Since cystatine-C levels during normal and high salt diet were comparable, the BP rise during high salt seems independent of renal dysfunction.

Ferrostatin-1 Attenuates Mechanical Hypersensitivity in Rats with Streptozotocin-Induced Diabetes by Inhibiting Spinal Ferroptosis

2021 ◽  
Author(s):  
Xiang Li ◽  
Yifan Deng ◽  
Ping Xiang ◽  
Jingyi Du ◽  
Jianfen Liang
Keyword(s):  
Lipid Peroxidation ◽  
Therapeutic Strategy ◽  
Intraperitoneal Administration ◽  
Mitochondrial Morphology ◽  
Continuous Administration ◽  
Once Daily ◽  
Mechanical Hypersensitivity ◽  
Expression Levels ◽  
Morphological Alterations ◽  
Streptozotocin Induced Diabetes

Abstract Diabetic neuropathic pain (DNP) is a highly prevalent complication of diabetes mellitus (DM) without effective treatments. The present study aimed to explore the effects of ferrostatin-1 (Fer-1) on mechanical hypersensitivity and spinal ferroptosis in rats with DM induced with streptozotocin (STZ). One week after STZ injection, the DM rats intraperitoneally received Fer-1 (2 μmol/kg) or a vehicle (1% DMSO) once daily for consecutive two weeks. The paw mechanical withdrawal thresholds (PMWT) were assessed weekly to investigate the nociceptive threshold. Biochemical and morphological alterations associated with spinal ferroptosis, including iron content, lipid peroxidation assays, the activities of anti-acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and mitochondrial morphology, were also evaluated. Decreased PMWT and significant changes in ferroptosis-associated markers, such as iron overload, lipid peroxidation, increased expression levels of ACSL4 and decreased expression levels of GPX4, and disrupted morphological features in mitochondria were found in rats with STZ-induced DM. These effects were significantly attenuated via intraperitoneal administration of the ferroptosis inhibitor Fer-1. Our findings indicated the involvement of iron-dependent ferroptosis in the spinal cords of rats with STZ-induced DM, and highlighted the effect of continuous administration of ferroptosis inhibitors such as Fer-1 on hypersensitivity in DM rats. These results suggest that inhibition of ferroptosis might be a potential therapeutic strategy in DNP treatment.

RENAL TOXICITY AND PHARMACOKINETICS OF WEEKLY LOW DOSE CISPLATIN ADMINISTERED WITH HYPERTHERMIA AND RADIATION

1991 ◽  
pp. 281
Author(s):  
D.L. FRAZIER ◽  
E. KLEBANOW ◽  
M. PANJEHPOUR ◽  
G. DANIEL ◽  
M.A. BARNHILL ◽  
...  
Keyword(s):  
Low Dose ◽  
Renal Toxicity

scholarly journals Effect of Fasting on Temporal Variation in the Nephrotoxicity of Amphotericin B in Rats

1999 ◽  
Vol 43 (3) ◽  
pp. 520-524 ◽  
Author(s):  
Michel LeBrun ◽  
Louis Grenier ◽  
Michel G. Bergeron ◽  
Louise Thibault ◽  
Gaston Labrecque ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Serum Creatinine Level ◽  
Temporal Variation ◽  
Amphotericin B ◽  
Creatinine Level ◽  
Renal Toxicity ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Similar Data ◽  
Ad Libitum

ABSTRACT Evidence for temporal variation in the nephrotoxicity of amphotericin B was recently reported in experimental animals. The role of food in these variations was determined by studying the effect of a short fasting period on the temporal variation in the renal toxicity of amphotericin B. Twenty-eight normally fed and 28 fasted female Sprague-Dawley rats were used. Food was available ad libitum to the fed rats, while the fasted animals were fasted 12 h before and 24 h after amphotericin B injection to minimize stress for the animals. Water was available ad libitum to both groups of rats, which were maintained on a 14-h light, 10-h dark regimen (light on at 0600 h). Renal toxicity was determined by comparing the levels of excretion of renal enzyme and the serum creatinine and blood urea nitrogen (BUN) levels at the time of the maximal (0700 h) or the minimal (1900 h) nephrotoxicity after the intraperitoneal administration of a single dose of dextrose (5%; control group) or amphotericin B (50 mg/kg of body weight; treated group) to the rats. The nephrotoxicities obtained after amphotericin B administration at both times of day were compared to the nephrotoxicities observed for time-matched controls. In fed animals, the 24-h urinary excretion ofN-acetyl-β-d-glucosaminidase and β-galactosidase was significantly higher when amphotericin B was injected at 0700 and 1900 h. The excretion of these two enzymes was reduced significantly (P < 0.05) in fasting rats, and this effect was larger at 0700 h (P < 0.05) than at 1900 h. The serum creatinine level was also significantly higher (P < 0.05) in fed animals treated at 0700 h than in fed animals treated at 1900 h. Fasting reduced significantly (P < 0.05) the increase in the serum creatinine level, and this effect was larger in the animals treated at 0700 h. Similar data were obtained for BUN levels. Amphotericin B accumulation was significantly higher (P < 0.05) in the renal cortexes of fed rats than in those of fasted animals, but there was no difference according to the time of injection. These results demonstrated that fasting reduces the nephrotoxicity of amphotericin B and that food availability is of crucial importance in the temporal variation in the renal toxicity of amphotericin B in rats.

scholarly journals Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Robin Paudel ◽  
Prerna Dogra ◽  
Saurav Suman ◽  
Saurav Acharya ◽  
Jyoti Matta
Keyword(s):  
Adverse Effect ◽  
Renal Failure ◽  
Drug Toxicity ◽  
Unusual Case ◽  
Renal Toxicity ◽  
Wide Spectrum ◽  
Polysorbate 80 ◽  
Ventricular Tachyarrhythmias ◽  
Case Review ◽  
Idiosyncratic Reaction

Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

scholarly journals Evaluation of isoniazid-oxidative reactions in mice model

2019 ◽  
Vol 9 (6) ◽  
pp. 36-37
Author(s):  
Kamel Mokhnache ◽  
Ahlem Karbab ◽  
Soraya Madoui ◽  
Hanane Khither ◽  
El-Khamsa Soltani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adverse Effect ◽  
Lipid Peroxidation ◽  
Control Group ◽  
Mice Model ◽  
Oxidative Reactions

In this study the anti-tubercular drug; isoniazid (INH) was investigated for their adverse effect; the oxidative stress. This effect was evaluated by using mice model, at the dose of 151 mg/kg.  We found that oxidative stress induced by INH is associated with lipid peroxidation expressed by the increase in the level of MDA from 76.9 ± 1.74 to 79.61 ± 2.67 nmol/g tissue. The oxidative stress of INH is accompanied by a decrease in reduced GSH level (from 79.9 ± 12 μmol / mg  to 68.48 ± 4.28 μmol / mg compared to of the control group). After treatment with INH at 151 mg/kg, a decrease in CAT activities occurred compared to control (2.53 ± 0.39 U/mg Pr vs 5.07 ± 0.73 U/mg Pr). Keywords: isoniazid, oxidative stress, MDA, GSH, CAT

Low‐dose curcumin‐loaded Eudragit L‐100‐nanocapsules in the diet of dairy sheep increases antioxidant levels and reduces lipid peroxidation in milk

2019 ◽  
Vol 43 (8) ◽  
Author(s):  
Antonise M. Jaguezeski ◽  
Samanta S. Gündel ◽  
Fernanda R. Favarin ◽  
André Gündel ◽  
Carine F. Souza ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Low Dose ◽  
Dairy Sheep
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