Effects of uranium depletion on 1α-hydroxylase in kidney of rats

2010 ◽  
Vol 30 (7) ◽  
pp. 786-790 ◽  
Author(s):  
Minfen Yan ◽  
Gaoren Zhong ◽  
Linfeng Gao ◽  
Xiqiao Xia ◽  
Lihua Wang ◽  
...  
Keyword(s):  
Active Form ◽  
Underlying Mechanism ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Sprague Dawley Rats ◽  
Dose Levels ◽  
Medium Dose

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)2D3 in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)2D3 after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.

scholarly journals Androgenic Effects of Cinnamomum camphora in Male Sprague-dawley Rats

2019 ◽  
pp. 1-13
Author(s):  
O. H. Ayoade ◽  
G. G. Akunna ◽  
F. I. Duru
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Activity Level ◽  
Control Group ◽  
High Dose ◽  
Activity Levels ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Medium Dose

This study evaluated camphora-induced androgenic and histopathological changes in male Sprague-Dawley rats. Thirty-five animals weighing 200 g±20 g were used for this study and randomly divided equally into five groups, with seven rats in each group. Group A animals (normal control group) were served water and rat chow only; Groups B-D (treatment groups) were orally administered camphora in doses of 1 g/kg (Low-dose), 2 g/kg (Medium-dose) and 4 g/kg (High-dose) respectively while Group E (vehicle group) were orally administered 6 mL/kg olive oil (a solvent for camphora) per day for 56 days. There was a significant decrease (P< .05) in activity levels of Follicle-Stimulating Hormone (FSH); Superoxide Dismutase (SOD) when the treatment was compared with the control group. Also, a significant decrease (P< .05) in activity level of FSH was observed when the Medium-dose group was compared with Low-dose group. Insignificant irregular pattern in activity level of Testosterone was observed across the treatment groups when compared with the control. However, a significant increase (P< .05) in activity level of Testosterone was observed when the High-dose group was compared with the Medium-dose group. There was a significant increase (P< .05) in activity levels of Luteinizing Hormone (LH) and Malondialdehyde (MDA) when the treatment was compared with the control group. Semen analysis showed reduction in sperm concentration, motility and morphology with increasing concentration of camphora. Significant decrease was recorded in testicular weight when High-dose group was compared to Control and Low-dose groups. Histopathological changes were seen in the testes of the camphor administered groups, ranging from mild disintegrated interstitial tissues in Low-dose to severe degeneration and disintegration of both seminiferous and interstitial tissues in the testes in the Medium-dose and High-dose groups. In conclusion, camphora had androgenic and toxic effects on testis and may cause testicular tissue damage.

scholarly journals Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-25
Author(s):  
Gajanan Deshmukh ◽  
Suresh B. Venkataramaiah ◽  
Chandrashekar M. Doreswamy ◽  
Mohan C. Umesh ◽  
Rajesh B. Subbanna ◽  
...  
Keyword(s):  
Biologically Active ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Endogenous Antioxidant ◽  
In Vitro Genotoxicity

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

scholarly journals Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

2019 ◽  
Vol 74 (2) ◽  
pp. 353-370 ◽  
Author(s):  
Li Tian ◽  
Weibin Qian ◽  
Qiuhai Qian ◽  
Wei Zhang ◽  
Xinrui Cai
Keyword(s):  
Low Dose ◽  
Area Postrema ◽  
Biologically Active ◽  
Control Group ◽  
High Dose ◽  
Delayed Emesis ◽  
Blank Control Group ◽  
Qrt Pcr ◽  
Underlying Mechanisms ◽  
Different Doses

Abstract Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract

Effects of TRH on thyrotroph function and number in rat pituitaries transplanted to renal capsule

1986 ◽  
Vol 251 (5) ◽  
pp. E563-E568
Author(s):  
S. Amr ◽  
S. S. Lippman ◽  
B. D. Weintraub
Keyword(s):  
Biologically Active ◽  
Constant Infusion ◽  
Control Group ◽  
Mrna Levels ◽  
Renal Capsule ◽  
Sprague Dawley ◽  
Subunit Mrna ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
Hypothalamic Influence

We investigated the function of thyrotrophs in rat pituitaries that were transplanted under the renal capsule of 3-wk-old male Sprague-Dawley rats, which were either intact or hypophysectomized. Groups of 12 animals were implanted with osmotic minipumps that delivered a constant infusion of either thyrotropin-releasing hormone (TRH; 1 mg X kg-1 X day-1) or normal saline for 1 wk. In hypophysectomized rats, TRH infusion led to the appearance of substantial amounts of biologically active serum TSH and prevented the hypothyroidism that occurred in the control group. However, TRH did not change the transplant contents of DNA, immunoactive TSH, and mRNA levels for TSH subunits. Comparison of sellar and renal pituitary tissues, obtained from intact rats after 1 wk of either saline or TRH infusion, showed that removal of the pituitary from hypothalamic influence resulted in a 90% depletion of the thyrotroph TSH content. TRH infusion depleted only 63% of the TSH content of sellar thyrotrophs. The mRNA levels for TSH beta-subunit were similar in sellar and transplanted pituitaries and did not significantly change after TRH infusion. When immunocytochemically stained using rat TSH antiserum, the thyrotrophs in pituitary transplants were morphologically and numerically indistinguishable from the thyrotrophs in sellar pituitaries, in the presence or absence of TRH. These data indicate that in transplanted pituitary, for up to 1 wk of a constant infusion, TRH does not significantly affect either the number of thyrotrophs or their ability to synthesize TSH subunit mRNA. However, it is required to maintain released TSH in circulation, since TSH levels were low in the absence of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeated-Dose and Subchronic Toxicity Studies of 2,2,2-Trichloroethanol in Sprague-Dawley Rats

1991 ◽  
Vol 10 (2) ◽  
pp. 223-232
Author(s):  
J. Peter Bercz ◽  
Merrel Robinson ◽  
Lucille M. Garner ◽  
Norbert P. Page ◽  
Greg R. Olson
Keyword(s):  
Toxic Effect ◽  
Clinical Symptoms ◽  
Clinical Chemistry ◽  
Lactic Dehydrogenase ◽  
Target Organ ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Levels

Male and female Sprague-Dawley rats were administered 2,2,2-trichloroethanol (TCE) by gavage for 14 or 90 consecutive days. The gavage solution consisted of TCE dissolved in distilled water, containing 10% Emulphor. Doses of 37.5, 75, 150, and 300 mg/kg/day in the 14-day study and 40, 80, 160, and 320 mg/kg/day for the 90-day study were employed. Evaluation of clinical symptoms, clinical chemistry, and pathology examinations did not reveal a specific toxic effect or identify a target organ. In male rats an increase of red blood cells (RBCs) and hematocrit (Hct) in both 14- and 90-day studies, as well as increased hemoglobin (Hgb) in the 90-day study was observed at the highest dose level. In the high-dose females only increase of Hgb was seen in the 14-day study. These hematopoietic indices were not accompanied by commensurate changes in reticulocytes, mean corpuscular volumes or spleen weights. Serum lactic dehydrogenase (LDH) levels were increased in males at the two highest dose levels of both studies. Other changes in chemistries were sporadic in nature and did not appear to be dose related. Collectively, there was no basis to identify a target organ. The RBC and LDH levels did not correlate with other biochemical or pathology results and did not support the hypothesis that they represent a specific toxic effect. Based on the lack of detectable toxicity of TCE at the highest doses tested in rats, the following lowest observed adverse effect levels (LOAEL) were assigned for this chemical: in the 14-day exposure, 300 mg/kg/day for both sexes; in the 90-day protocol, 320 mg/kg/day for female; and 160 mg/kg/day for male rats.

scholarly journals Subacute Intramuscular Toxicity of the Acetylcholinesterase Reactivating Agent HI-6 in Rats and Dogs

1993 ◽  
Vol 12 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Barry S. Levine ◽  
Michael J. Tomlinson
Keyword(s):  
Injection Site ◽  
Creatine Kinase Activity ◽  
High Dose ◽  
Sprague Dawley ◽  
Hi 6 ◽  
Sprague Dawley Rats ◽  
High Doses ◽  
Hematology Parameters ◽  
Dose Levels ◽  
Dose Injection

Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture, and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters were unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.

scholarly journals Impact of Moriamin Forte on Testicular and Epididymal Damage in Rats with Oligoasthenospermia

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xing Zhou ◽  
Guo-Wei Zhang ◽  
Wei-Ning Liang ◽  
Yi-Ze Li ◽  
Song Xu ◽  
...  
Keyword(s):  
Group Treatment ◽  
Sperm Count ◽  
Testicular Tissue ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Antioxidase Activity ◽  
Motility Of Sperm ◽  
Related Proteins

To investigate the effect and mechanism of action of Moriamin Forte (MF) on oligoasthenospermia (OA) in rats exposed to multiglycosides of Tripterygium wilfordii (GTW), forty male Sprague Dawley rats were randomly divided into four groups. Rats in the control group were treated with 0.5% sodium carboxymethyl cellulose. The remaining rats were administered GTW (30 mg/kg/d) for 40 d to establish an OA model. Concurrently, the groups were treated with normal saline and low-dose (100 mg/kg/d) and high-dose (200 mg/kg/d) MF, respectively. After treatment, the number and motility of sperm cells were examined. Testicular and epididymal histomorphology changes were observed. Antioxidant indicators (SOD, CAT, MDA, TAC, and Nrf2) in testicular and epididymal tissues were detected. Apoptotic and antiapoptotic indicators (Bax and Bcl2 expression) in the testicular tissue were measured by immunohistochemistry. GTW decreased sperm count and motility, damaged testicular and epididymis tissues, impaired antioxidase activity, and increased tissue MDA levels. Meanwhile, GTW upregulated the expression of Bax and downregulated the expression of Bcl2. Western blot analysis demonstrated a decrease in the Nrf2 expression in the model group. Treatment with MF improved sperm count and motility, as well as inhibited the rate of apoptosis in the rat reproductive system. Moreover, MF improved the activity of antioxidants and increased the relative expression of the antioxidant pathway-related protein Nrf2. In conclusion, MF may reverse the GTW-induced OA by modulating the expression of apoptotic and antioxidant pathway-related proteins. This study may provide a pharmacological foundation for the use of MF in OA treatment.

scholarly journals Constipation-relieving effect of L-arabinose

2020 ◽  
Vol 19 (1) ◽  
pp. 95-99
Author(s):  
Hao Wang ◽  
Wenxian Zhang ◽  
Bin Jiang
Keyword(s):  
Mouse Model ◽  
Control Group ◽  
High Dose ◽  
Fecal Pellets ◽  
Experimental Mouse Model ◽  
Model Control ◽  
Model Control Group ◽  
Experimental Mouse ◽  
Dose Levels ◽  
Medium Dose

Purpose: To investigate the mitigating effect of L-arabinose on constipation in a mouse model of experimental constipation.Methods: Kunming mice were used as experimental animals to establish a constipation model. Intestinal propulsion, first defecation time, number of defecation pellets, and the weight of defecation pellets in 5 h were measured. L-Arabinose was given at 3 dose levels, viz, low dose (0.5 g/kg/day),medium dose (0.75 g/kg/day), and high dose (2.5 g/kg/day), and their effects on constipation were compared with that of the model control group.Results: Compared with the model control group, there were significant differences in ink propulsion (F= 22.67, p < 0.05); time taken for first black stool to appear (F = 19.51, p < 0.05), number of fecal pellets (F = 12.22, p < 0.05), and fecal weight (F = 5, p < 0.05) in the L-arabinose groups.Conclusion: L-Arabinose relieves constipation symptoms in an experimental mouse model of constipation. Therefore, L-arabinose may be useful in the management of patients with constipation, but further studies in humans are required to ascertain this. Keywords: L-Arabinose, Fecal pellets/grains, Constipation, Stool, Intestinal propulsion

scholarly journals Effects of Chronic Exposure to Sodium Arsenite on Expressions of VEGF and VEGFR2 Proteins in the Epididymis of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Dai Yan-Ping ◽  
Gao Xiao-Qin ◽  
Ma Xiao Ping ◽  
Yue Ying Quan
Keyword(s):  
Sodium Arsenite ◽  
Low Dose ◽  
Infected Group ◽  
Control Group ◽  
High Dose ◽  
Apoptotic Cells ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group Protein

Objective. To study the expressions of VEGF and VEGFR2 at protein level in the epididymis of rats with arsenism. Methods. Forty male Sprague-Dawley rats were randomly divided into four groups: the high dose arsenic infected group (60.0 mg/L in water), the middle dose arsenic infected group (12.0 mg/L in water), the low dose arsenic infected group (2.4 mg/L in water), and the control group (distilled water). Rats were treated with arsenic through drinking water for 6 consecutive months. At the end of the experiment, the average densitometry values of apoptotic cells in epididymis tubules were determined by TUNEL method; the protein and mRNA levels of VEGF and VEGFR2 were observed by immunohistochemistry, Western blot, and real time fluorescent quantitative PCR, respectively. Results. Compared with the control group, in each infected group, the average densitometry values of apoptotic cells in the epididymis tubules were significantly lower. Compared with control group, protein and mRNA levels of VEGF and VEGFR2 in each infected group were obviously declined. The correlations between protein and mRNA levels of VEGF and VEGFR2 were positively exhibited (r = 0.843, 0.869, p < 0.05). Conclusions. Arsenism affects the expressions of VEGF and VEGFR2 in the epididymis of rats and results in apoptosis of pathophysiology of male infertility.

scholarly journals Metabolomics of Aurantio-Obtusin-Induced Hepatotoxicity in Rats for Discovery of Potential Biomarkers

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3452 ◽  
Author(s):  
Longlong Xu ◽  
Jian Li ◽  
Xianglin Tang ◽  
Yuguang Wang ◽  
Zengchun Ma ◽  
...  
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Hematological Indices ◽  
Main Components ◽  
Kg Medium

Aurantio-obtusin is an anthraquinone derived from Cassia obtusifolia (cassiae semen). It is also used as a tool and a detection index for the identification of cassiae semen, as stipulated by the Chinese Pharmacopoeia. Anthraquinones, the main components in cassiae semen, have been reported to show hepatotoxicity. This study investigates the hepatotoxicity of aurantio-obtusin in male Sprague–Dawley rats. We randomly divided the animals into a blank control group and treated three test groups with different doses of aurantio-obtusin: Low dose (4 mg/kg), medium dose (40 mg/kg), and high dose (200 mg/kg). Each group was treated with aurantio-obtusin for 28 days, whereas the control group was administered an equal volume of 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution. Subsequently, we conducted biochemical, hematological, and pathological investigations and determined the weight of different organs. We used serum metabolomics to identify possible biomarkers related to hepatotoxicity. The low-dose group showed no significant liver injury, whereas the medium- and high-dose groups manifested obvious liver injury. Compared with the control group, the test groups showed an increase in alanine transaminase, aspartate transaminase, and alkaline phosphatase levels. The liver organ coefficient also significantly increased. Additionally, we found significant changes in the hematological indices. Metabolomics analysis showed that aurantio-obtusin induced 28 endogenous markers related to liver injury. Our data indicate that aurantio-obtusin induces hepatotoxicity in rat liver in a dose-dependent manner and is mediated by pathways involving bile acids, fatty acids, amino acids, and energy metabolism. In particular, changes in bile acid content during treatment with therapeutic agents containing aurantio-obtusin deserve increased attention.

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