scholarly journals Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 353 ◽  
Author(s):  
Xiaoyu Ji ◽  
Mengbi Yang ◽  
Ka Hang Or ◽  
Wan Sze Yim ◽  
Zhong Zuo
Keyword(s):  
Ultra Performance Liquid Chromatography ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Relevant Dose ◽  
Radix Aconiti ◽  
Toxic Alkaloids

Although Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practice are still not known. To give a comprehensive understanding of Fuzi-induced toxicities, current study is proposed aiming to investigate the biodistribution of the six toxic alkaloids in Fuzi, namely Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), Benzoylaconine (BAC), Benzoylhypaconine (BHA) and Benzoylmesaconine (BMA), after its oral administrations at clinically relevant dosing regimen. A ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for simultaneous quantification of six toxic alkaloids in plasma, urine and major organs of Sprague Dawley rats after oral administrations of two commonly used Fuzi preparations, namely Heishunpian and Paofupian, at their clinically relevant dose for single and 15-days. Among the studied toxic alkaloids and organs, BMA demonstrated the highest concentrations in all studied organs with liver containing the highest amount of the studied alkaloids, indicating their potential hepatotoxicity. Moreover, tissue accumulation of toxic alkaloids after multiple dose was observed, suggesting the needs for dose adjustment and more attention to the toxicities induced by chronic use of Fuzi in patients.

Chemopreventive effect of diclofenac on mammary carcinogenesis in Sprague-Dawley rats

Biologia ◽  
2013 ◽  
Vol 68 (4) ◽  
Author(s):  
Peter Orendáš ◽  
Ivan Ahlers ◽  
Bianka Bojková ◽  
Monika Kassayová ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Tap Water ◽  
Mammary Carcinogenesis ◽  
Female Rats ◽  
Sprague Dawley ◽  
Short Term ◽  
Antiinflammatory Drugs ◽  
Sprague Dawley Rats ◽  
Term Administration ◽  
Chemopreventive Effect

AbstractChemopreventive effect of non-steroidal antiinflammatory drugs (NSAIDs) in mammary carcinogenesis was reported in several studies. In this study, the effect of a nonselective cyclooxygenase inhibitor diclofenac (DICLO) in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats was evaluated. NMU was administered to animals intraperitoneally in two doses of 50 mg kg−1 b.w. within postnatal days 42-48. In experiment A (short-term administration), DICLO was administrated intramuscularly (5 mg kg−1 b.w.) every other day, starting 3 days before and for subsequent 25 days after first NMU injection. In experiment B (long-term administration), DICLO was administered in tap water (0.01 mg ml−1) continually, starting 7 days before and for subsequent 22 weeks after first NMU dose. The study was terminated 22 weeks after the first dose of NMU in both experiments. After DICLO treatment, tumor frequency per group was reduced in both variants of drug administration: in experiment A by 38% and in experiment B by 39.5%. Moreover, DICLO decreased tumor incidence by 11.5% and delayed tumor latency by 14 days in experiment B. In our preventive-curative experiments DICLO decreased some parameters of NMU-induced rat mammary carcinogenesis, mainly the tumor frequency.

scholarly journals Pharmacokinetics of ligustroflavone in rats and tissue distribution in mice by UPLC–MS/MS

2020 ◽  
Vol 32 (2) ◽  
pp. 102-106 ◽  
Author(s):  
Quan Zhou ◽  
Zhiguang Zhang ◽  
Peiwu Geng ◽  
Bingge Huang ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Intraperitoneal Administration ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Mouse Tissues ◽  
Extensive Metabolism ◽  
Liquid Chromatography Tandem Mass ◽  
Group 1

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for quantification of ligustroflavone, which was then applied in pharmacokinetics study in rat and tissue distribution in mouse. Twelve male Sprague Dawley rats were used for pharmacokinetics after intravenous (2 or 8 mg/kg) administration of ligustroflavone, six rats for each dose. Twenty-five mice were randomly divided into 5 groups (5 mice for each group, 1 group for each time point) and received 16 mg/kg ligustroflavone via intraperitoneal administration. The linear range of the calibration curve was over 2–2000 ng/mL for ligustroflavone in rat plasma and mouse tissues. The intra-day and inter-day precision expressed in % RSD were less than 14%, and the accuracy was between 88.5% and 108.4%. The tissue distribution results indicated that ligustroflavone diffuses rapidly and widely into major organs. The level of ligustroflavone was highest in the mouse liver, followed by the kidney, spleen, and lung. The overwhelming accumulation in the liver indicated that the liver was responsible for the extensive metabolism.

scholarly journals Effect of the Phragmitis Rhizoma Aqueous Extract on the Pharmacokinetics of Docetaxel in Rats

2019 ◽  
Vol 22 (5) ◽  
pp. 326-332
Author(s):  
Sarah Shin ◽  
No Soo Kim ◽  
Young Ah Kim ◽  
Hea Ry Oh ◽  
Ok-Sun Bang
Keyword(s):  
Aqueous Extract ◽  
Statistical Significance ◽  
Ultra Performance Liquid Chromatography ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Mass Spectrometry System ◽  
Phragmitis Rhizoma

Background: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. Aim and Objective: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague–Dawley rats. Materials & Methods: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. Results: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). Conclusion: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.

scholarly journals Unexpected short- and long-term effects of chronic adolescent HU-210 exposure on emotional behavior

2021 ◽  
Author(s):  
Miguel Farinha-Ferreira ◽  
Nádia Rei ◽  
Jo&atildeo Fonseca-Gomes ◽  
Catarina Miranda-Lourenço ◽  
Paula Serr&atildeo ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Emotional Behavior ◽  
Sprague Dawley ◽  
Long Term Effects ◽  
Negative Effects ◽  
Short Term ◽  
Receptor Agonists ◽  
Sprague Dawley Rats ◽  
Short And Long Term

Chronic adolescent cannabinoid receptor agonist exposure has been shown to lead to persistent increases in depressive-like behaviors. This has been a key obstacle to the development of cannabinoid-based therapeutics. However, most of the published work has been performed with only three compounds, namely ∆9-tetrahydrocannabinol, CP55,940 and WIN55,212-2. Hypothesizing that different compounds may lead to distinct outcomes, we herein used the highly potent CB1R/CB2R full agonist HU-210, and first aimed at replicating cannabinoid-induced long-lasting effects, by exposing adolescent female Sprague-Dawley rats to increasing doses of HU-210, for 11 days and testing them at adulthood, after a 30-day drug washout. Surprisingly, HU-210 did not significantly impact adult anxious- or depressive-like behaviors. We then tested whether chronic adolescent HU-210 treatment resulted in short-term (24h) alterations in depressive-like behavior. Remarkably, HU-210 treatment simultaneously induced marked antidepressant- and prodepressant-like responses, in the modified forced swim (mFST) and sucrose preference tests (SPT), respectively. Hypothesizing that mFST results were a misleading artifact of HU-210-induced behavioral hyperreactivity to stress, we assessed plasmatic noradrenaline and corticosterone levels, under basal conditions and following an acute swim-stress episode. Notably, we found that while HU-210 did not alter basal noradrenaline or corticosterone levels, it greatly augmented the stress-induced increase in both. Our results show that, contrary to previously studied cannabinoid receptor agonists, HU-210 does not induce persisting depressive-like alterations, despite inducing marked short-term increases in stress-induced reactivity. By showing that not all cannabinoid receptor agonists may induce long-term negative effects, these results hold significant relevance for the development of cannabinoid-based therapeutics.

Discordant aspects of aldosterone resistance in potassium depletion

1992 ◽  
Vol 262 (6) ◽  
pp. F972-F979 ◽  
Author(s):  
S. K. Mujais ◽  
Y. Chen ◽  
N. A. Nora
Keyword(s):  
Biochemical Response ◽  
Sprague Dawley ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
Pump Activity ◽  
Before And After ◽  
Collecting Tubules ◽  
Low K ◽  
K Depletion

Aldosterone resistance, defined as absent kaliuretic response to exogenous hormone, has been described in K depletion. It is not clear whether the absent kaliuresis is due to activation of K-conserving mechanisms or to failure of activation of the Na-K pump in cortical collecting tubules (CCT) by mineralocorticoids. Adrenalectomized male Sprague-Dawley rats were allocated to either a normal or low-K diet. Na-K pump activity (pmol.mm-1.h-1) in microdissected CCT and medullary collecting tubules (MCT, inner stripe of the outer medulla) was determined at 7 or 21 days after allocation to the dietary groups before and after exogenous aldosterone (50 micrograms twice daily, for 3 days). K depletion led to progressive hypertrophic changes in the CCT and MCT manifest in an increase in basal Na-K pump activity. In both K repletion and short-term K depletion (7 days), aldosterone led to the expected increase in CCT Na-K pump activity. With long-term K depletion, the CCT Na-K pump response to aldosterone was blunted. In the MCT where under normal conditions the Na-K pump is aldosterone unresponsive, an increasing aberrant responsiveness to the mineralocorticoid was observed with progressive K depletion. We conclude that apparent aldosterone resistance in short-term K depletion is likely due to activation of K-conserving mechanisms with early preservation of the CCT biochemical response to the hormone. With long-term K depletion, a blunted biochemical response to aldosterone may contribute to the absent kaliuretic response. In the MCT, K depletion led to the development of aberrant responsiveness to aldosterone.

scholarly journals Effect of a Short-Term and Long-Term Melatonin Administration on Mammary Carcinogenesis in Female Sprague-Dawley Rats Influenced by Repeated Psychoemotional Stress

2007 ◽  
Vol 76 (3) ◽  
pp. 371-377 ◽  
Author(s):  
M. Kassayová ◽  
E. Adámeková ◽  
B. Bojková ◽  
P. Kubatka ◽  
I. Ahlers ◽  
...  
Keyword(s):  
Mammary Carcinogenesis ◽  
Tumour Volume ◽  
Female Rats ◽  
Sprague Dawley ◽  
Short Term ◽  
Psychoemotional Stress ◽  
Sprague Dawley Rats ◽  
Melatonin Administration ◽  
Term Administration

The aim of this study was to evaluate the effect of melatonin (MEL) on N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats exposed to repeated psychoemotional stress - immobilization in boxes. NMU was applied intraperitoneally in two doses each of 50 mg/kg b.w. between 40 - 50 postnatal days. Melatonin was administered in drinking water at a concentration of 4 μg/ml daily from 15:00 h to 8:00 h. The application was initiated 5 days prior to the fi rst NMU dose and lasted 15 days, i.e. during the promotion phase of tumour development, or long-term until the end of the experiment (week 20). Immobilization (2 h per day) began on the third day after the second carcinogen application and lasted for 7 consecutive days. Short-term MEL administration to immobilized animals increased incidence by 22%, decreased tumour frequency per animal by 26% and reduced tumour volume gain (by 21%) when compared to the immobilized group without MEL application. Decreased frequency per animal by 28% and more than a 40% decrease in tumour volume gain and cumulative volume were the most pronounced changes in the animals drinking MEL until the end of the experiment. Long-term MEL administration reduced the number and size of mammary tumours more markedly than its short-term administration. Melatonin decreased certain attributes of mammary carcinogenesis in female rats influenced by psychoemotional stress.

scholarly journals The beneficial effect of long-term supplementation of vitamin C on renal mitochondrial disturbances in streptozotocin-induced diabetic rats

2011 ◽  
Vol 5 (2) ◽  
pp. 277-282
Author(s):  
Mariem Yusuksawad ◽  
Narongsak Chaiyabutr
Keyword(s):  
Vitamin C ◽  
Renal Dysfunction ◽  
Tap Water ◽  
Diabetic Rats ◽  
Mitochondrial Activity ◽  
Sprague Dawley ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
Respiration Control

Abstract Background: Oxidative stress induces renal dysfunction in diabetes, in which renal mitochondrial disturbance was implicated. Vitamin C (VC) supplementation may ameliorate the renal dysfunction in diabetics. However, it is not clear whether VC supplementation is effective for renal mitochondrial disturbances in diabetes. Objective: Investigate whether long-term continuous VC supplementation could ameliorate the renal mitochondrial disturbances in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-five male Sprague-Dawley rats were used, and diabetes was induced by an injection of STZ. The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and diabetic rats supplemented by vitamin C (STZ-VC). The CON and STZ rats were given tap water, while STZ-VC rats received VC (1 g/L) every day for eight, 24 and 52 weeks. The kidney was isolated and homogenized. Oxygen comsumption (Vo2) was measured in mitochondria homogenate using an oxygen consumption monitor. Based on Vo2 tracings, the respiration control index (RCI) and P/O ratio (= ADP/ O ratio) were measured at week 8, 24 and 52. Results: At week eight, using either glutamate plus malate (for site I) or succinate (for site II) as substrates, both RCI and P/O ratio were not significantly different among three groups. The P/O ratio in STZ and STZ-VC rats increased from eight to 52 weeks after VC supplementation. At week 24, the P/O ratio at site II was normalized in STZ-VC rat. The increased P/O ratio (only site I) and the increased RCI (only site II) of STZ-VC rats were slower than those of STZ rats. Conclusion: Short-term VC supplementation might not influence the renal mitochondrial activity. The long-term VC supplementation could ameliorate the mitochondrial disturbances induced in STZ-induced diabetic rats.

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