scholarly journals Unexpected Nephrotoxicity in Male Ablactated Rats Induced byCordyceps militaris: The Involvement of Oxidative Changes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaowen Zhou ◽  
Yi Yao
Keyword(s):  
Renal Cortex ◽  
Renal Toxicity ◽  
Kidney Injury ◽  
Female Rats ◽  
Male Rats ◽  
Reduced Form ◽  
High Dose ◽  
Protein Expressions ◽  
Kidney Injury Molecule 1 ◽  
Nutraceutical Products

Recently, many nutraceutical products containing the powdered or extracted parts ofC. militarishave become available for health care. Due to the increased morbidity and mortality, poisonings associated with the use of herbs have raised the universal attention. Herein, we carried out the 28-day repeated toxicity test in male and female ablactated rats (three weeks old) givenC. militarispowder orally at 0 (control), 1, 2, and 3 g/kg per day. Noticeable increments of serum aspartate and alanine aminotransferase (ALT and AST) levels were observed for both sexes, suggestive of weak hepatic toxicity. Nephrotoxicity characterized by tubular epithelium degeneration and necrosis was observed at the high dose, and the male rats were more susceptible to renal toxicity than female rats. In addition, the genes and protein expressions of novel markers of kidney toxicity, such as kidney injury molecule-1 (KIM-1) were enlarged in the renal cortex and the urine. Moreover,C. militaristreatment significantly decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. However, the ratio of glutathione oxidized form (GSSG)/glutathione reduced form (GSH) was increased byC. militaristreatment. We conclude that dietary contamination withC. militarismay have renal toxicity potentials, at least in part by causing oxidative damage to the kidney.

scholarly journals Drug-induced Obstructive and Retrograde Nephropathy Associated with α2u-globulin in Male Rats

2018 ◽  
Vol 47 (2) ◽  
pp. 138-149
Author(s):  
Björn Jacobsen ◽  
Christian Freichel ◽  
Anne Eichinger-Chapelon ◽  
Andreas Brink ◽  
Jean-Christophe Hoflack ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Female Rats ◽  
Male Rats ◽  
Mechanistic Study ◽  
Obstructive Nephropathy ◽  
Dependent Manner ◽  
Intact Male ◽  
Drug Induced ◽  
Specific Syndrome ◽  
Kidney Injury Molecule 1

The chemically induced accumulation of α2u-globulin protein in male rats causes specific renal lesions and subsequent nephropathy. Herein, we report additional parallel findings in the kidney of male rats consistent with obstructive and retrograde nephropathy. Kidney and urinary bladder samples were evaluated from Wistar rats treated with RG7129 for 2 week and 8 week and from an 8-week mechanistic study using females, intact and castrated males. Histopathological findings were present in intact males in all studies, including hyaline droplet accumulation and granular casts consistent with α2u-globulin nephropathy. In addition, tubular degeneration and regeneration, tubular changes extending from papilla to cortex, tubular dilation, and interstitial and luminal inflammation were observed consistent with retrograde and obstructive nephropathy. Renal and urinary lesions and their severity increased in a time- and dose-dependent manner. Urinalysis findings, including increases in leukocytes, protein, and in kidney biomarkers, kidney injury molecule 1 and clusterin, were present only in intact males. No treatment-related changes were observed in female rats or in castrated males. These results indicate that RG7129 induces α2u-globulin nephropathy, associated with retrograde and obstructive nephropathy secondary to precipitation in intact male rats only, constituting a species- and sex-specific syndrome that is not expected to occur in humans or other species.

scholarly journals Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  
Keyword(s):  
Rat Model ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Female Rats ◽  
Male Rats ◽  
Renal Diseases ◽  
Transgenic Rat ◽  
Increased Risk ◽  
Before And After

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.

Male gender increases sensitivity to renal injury in response to cholesterol loading

2003 ◽  
Vol 284 (4) ◽  
pp. F718-F726 ◽  
Author(s):  
Diana M. Attia ◽  
Roel Goldschmeding ◽  
Mahmoud A. Attia ◽  
Peter Boer ◽  
Hein A. Koomans ◽  
...  
Keyword(s):  
Renal Injury ◽  
Low Dose ◽  
Plasma Cholesterol ◽  
A Priori ◽  
No Synthase ◽  
Male Gender ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Cholesterol Feeding

Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol ( P < 0.001). Control males had lower renal NOS activity than control females (4.44 ± 0.18 vs. 7.46 ± 0.37 pmol · min−1 · mg protein−1; P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females ( P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.

Hepatic alpha 2 mu-globulin: a potential metabolic role in the rat proximal tubule

1996 ◽  
Vol 271 (3) ◽  
pp. F527-F538 ◽  
Author(s):  
S. C. Borkan ◽  
Y. H. Wang ◽  
K. T. Lam ◽  
P. Brecher ◽  
J. H. Schwartz
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Proximal Tubule ◽  
Glucose Oxidation ◽  
Renal Cortex ◽  
Female Rats ◽  
Male Rats ◽  
Normal Female ◽  
Fatty Acid Binding ◽  
Oxidation Rates

In the present study, we provide immunohistochemical and immunologic evidence to localize an abundant, 15.5-kDa protein to the soluble protein fraction of the proximal tubule. This 15.5-kDa protein binds fatty acids in vitro and has identity with amino acids 10-117 of alpha 2 mu-globulin (A2 fragment), a 19-kDa protein synthesized predominantly in the male liver. With reverse transcription-polymerase chain reaction, mRNA for A2 was detected in male liver but not in the male kidney. De novo accumulation of the 15.5-kDa protein was observed in the renal cortex of female rats given intravenous injections of purified 19-kDa protein (A2), suggesting intrarenal processing of the larger protein. The potential role of this protein in the proximal tubule, a site that utilizes fatty acids as an important metabolic substrate, was determined in isolated proximal tubule segments. Fatty acid and glucose oxidation rates were measured in three experimental models in which the 15.5-kDa protein was virtually absent: 1) uninephrectomized male rats treated with deoxycorticosterone acetate and salt, 2) male rats subjected to bilateral adrenalectomy, and 3) normal female rats. In the absence of the 15.5-kDa protein, fatty acid oxidation rates decreased by 30-55%, whereas glucose oxidation significantly increased in all three models. In female renal cortex, depletion of the 15.5-kDa protein was associated with a rise in heart fatty acid binding protein, an alternative intracellular transporter of fatty acids. These data support the hypothesis that a proteolytic cleavage product of hepatic alpha 2 mu-globulin may facilitate the oxidation of oleate, a hydrophobic ligand, in the proximal tubule.

Influence of in utero di-n-hexyl phthalate and di-cyclohexyl phthalate exposure on the endocrine glands and T3, T4, and TSH hormone levels of male and female rats: Postnatal outcomes

2020 ◽  
Vol 36 (6) ◽  
pp. 399-416
Author(s):  
Nurhayat Barlas ◽  
Emre Göktekin ◽  
Gözde Karabulut
Keyword(s):  
Pituitary Gland ◽  
Dose Group ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Hormone Levels ◽  
Male And Female Rats ◽  
Endocrine Organs ◽  
Body Weights ◽  
Juvenile Stages

The present study was designed to evaluate the effects of di- n-hexyl phthalate (DHP) and di-cyclohexyl phthalate (DCHP) on endocrine organs in rats. Oil control, 20-, 100-, and 500 mg/kg dose groups were selected and administered to pregnant rats on gestational days 6–19 by oral gavage. The neonatal stages of rats continued until postnatal day 20 and the- juvenile stages of rats continued until postnatal day of 32. The rats were allowed to mature until the neonatal and juvenile stages and there after, they were divided into four groups corresponding to the treatment levels. Body and organ weights were recorded, serum was collected, and thyroid, pancreas, pituitary gland, and adrenal gland were removed. There was a decrease in body weights in the 20- and 500mg/kg DHP and in the 20-mg/kg DCHP dose groups in neonatal male rats. In contrast, for female rats, there was an increase in body weights in the 100-mg/kg DCHP dose group and there was a decrease in body weights in the 500-mg/kg DHP dose group. Body weights were increased at 20 and 500 mg/kg in the DHP-exposed juvenile male rats. Serum thyroid-stimulating hormone (TSH) levels were increased in neonatal male rats, while they were increased in the 100-mg/kg DHP group of neonatal and juvenile female rats. Serum triiodothyronine (T3) levels were increased at the high dose of DHP for neonatal male rats and at the low and high dose levels of DCHP for female rats. Serum thyroxine (T4) levels were increased in neonatal rats for DHP. Also, some histopathological changes were observed in the thyroid, pancreas, adrenal, and pituitary gland. In conclusion, it was shown that DHP and DCHP caused negative effects on T3, T4, and TSH hormone levels.

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu
Keyword(s):  
Lymph Node ◽  
Bisphenol A ◽  
Tissue Damage ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Organ Function ◽  
Pregnant Rats

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

Studies of the Toxicological Potential of Capsinoids: VIII. A 13-Week Toxicity Study of Commercial-Grade Dihydrocapsiate in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 101-118 ◽  
Author(s):  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Food Consumption ◽  
Water Intake ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Organ Weights

Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100,300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses ≤300 mg/kg or in females at any of the doses tested (≤1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.

Gene expression approach to evaluate kidney injury molecule-1 (KIM-1) as a predictive marker for renal toxicity

2010 ◽  
Vol 196 ◽  
pp. S245
Author(s):  
A. Chiusolo ◽  
R. Defazio ◽  
P. Cristofori ◽  
M. Mongillo ◽  
E. Zanetto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Toxicity ◽  
Kidney Injury ◽  
Predictive Marker ◽  
Kidney Injury Molecule 1

Kidney Injury Molecule-1 and its association with delayed clearance and drug exposure in pediatric oncology patients treated with high dose methotrexate.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 10034-10034
Author(s):  
Andrew J. Bukowinski ◽  
Tomoyuki Mizuno ◽  
Tsuyoshi Fukuda ◽  
A.a. Vinks ◽  
Stuart Goldstein ◽  
...  
Keyword(s):  
Pediatric Oncology ◽  
Drug Exposure ◽  
Kidney Injury ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Oncology Patients ◽  
Dose Methotrexate ◽  
Kidney Injury Molecule 1

Subchronic Toxicity of Thalidomide in Rodents After 13 Weeks of Oral Administration

1999 ◽  
Vol 18 (5) ◽  
pp. 337-352 ◽  
Author(s):  
Steve K. Teo ◽  
Nancy J. Trigg ◽  
Mary E. Shaw ◽  
J. Michael Morgan ◽  
Steve D. Thomas
Keyword(s):  
Food Consumption ◽  
Dose Response ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
Lumbar Spinal Cord ◽  
High Dose ◽  
Significant Finding ◽  
Lower Body ◽  
Body Weights

The subchronic toxicology of thalidomide was determined in CD-1 mice and F344 rats. Animals (10/sex/dose) were orally dosed at 30,300, and 3000 mg/kg/day over 13 weeks. Control animals were given 1% carboxymethylcellulose. No thalidomide-related mortality occurred throughout the study. Some species and sex differences were seen. In mice, thalidomide had no effect on body weight, food consumption, ophthalmic function or clinical chemistry/hematology, but a dose-dependent orange-pink urine was observed in both sexes. The discoloration was probably due to chromogenic breakdown products of thalidomide. The only significant finding in the mouse study was dose-related hepatic centrilobular hypertrophy in the males. This appeared only at the highest dose in the females. The hypertrophy was correlated with increased liver weight for the high dose of both sexes suggesting enzyme induction. In rats, thalidomide produced lower body weights in both sexes compared to control with a dose-response more evident in males. Male rats dosed at 30, 300, and 3000 mg/kg had body weights that were 8, 11, and 19% below control weight just before necropsy. Corresponding female rats were only 6–7% below control weights at all dose levels. Lower food consumption was observed in male rats and varied between 6–13% below control with no dose-response. Decreased forelimb strength was noted in males and could be due to the lower body weights. Functional observational battery tests and histopathology of the sural nerve and lumbar spinal cord sections suggested that the rat did not develop thalidomide-induced peripheral neuropathy. Mild anemia and leukopenia were seen only in some treated males. A decrease in total and free T4 was more consistent in females. Both sexes had lower thymus weights with no histological correlate compared to control. The no-observed-adverse-effect level for mice and female rats were 3000 mg/kg and 30 mg/kg for male rats.

Sign in / Sign up

Export Citation Format

Share Document