Chronic Toxicity Study of Aqueous Roots Extract of Rauvolfia vomitoria AFZEL on Haematological Parameters in Wistar Rats

Rauvolfia vomitoria Afzel. (Apocynaceae) is a plant used in traditional medicine in Côte d'Ivoire for the treatment of several conditions. This work aims to evaluate the effects of repeated oral administration of the aqueous roots extract Rauvolfia vomitoria AFZEL (AERv) on haematological parameters in Wistar rats. Thus, 100 healthy rats were divided into four groups (T, A, B, C) of 20 rats each. The sub groups Ts and Cs from the groups T and C included 10 rats (5 males and 5 females) were formed for a reversibility study. After 6 months (180 days) of the experiment, the sub groups rats Ts and Cs were no more treated with the extract till the 210th day (7 months), day of their sacrifice to verify the reversibility and/or delayed effects of AERv. The erythrocyte, platelet and leukocyte parameters were determined. Results showed that AERv caused a significant decrease in erythrocyte and thrombocyte parameters with the high dose (1000 mg/kg bw) while an increase in leukocyte parameters was noted in a dose-dependent manner. The aqueous extract of the barkless roots is not harmful at the therapeutic dose of 700 mg/kg bw on the haematological parameters. After stoping administration the effects were reversible.

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Glucocorticoid-Induced, Morpho-Functional Alterations in Pancreatic Beta Cells of Wistar Rats

Asian Journal of Research in Medical and Pharmaceutical Sciences ◽

10.9734/ajrimps/2019/v6i230099 ◽

2019 ◽

pp. 1-9

Author(s):

A. Aigbiremolen ◽

M. A. Omoirri ◽

O. A. Udi ◽

S. E. Iloh ◽

M. Ogbonnaya

Keyword(s):

Vitamin E ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Wistar Rats ◽

Morphological Changes ◽

High Dose ◽

Dependent Manner ◽

Functional Changes ◽

Cell Functions ◽

Dose Dependent

Background: Though prolonged use of glucocorticoids has been reported to promote adverse effects, traditionally, high-dose glucocorticoids have been implicated in immune-suppression following organ transplant with Cortisone being a well-known artificial glucocorticoid. Objectives: This study investigated the histo-architectural and functional changes in pancreatic beta cells due to Cortisone administration. Materials and Methods: Forty two (42) Wistar rats (140 – 200 kg) were assigned into seven groups of six (6) rats each with group A acting as a control. While groups B and C were respectively treated with 0.1 mg/kg and 0.3 mg/kg of Cortisone, groups D and E received 0.1 mg/kg and 0.3 mg/kg of Cortisone respectively plus 33 mg/kg of Ketoconazole; whereas, groups F and G were respectively given 0.1 mg/kg and 0.3 mg/kg of Cortisone alongside 150 mg/kg of Vitamin E each for twenty-eight (28) days. After 28 days of administration, rats were euthanized and blood samples collected for insulin assay. Pancreatic tissues were also harvested and observed for histo-morphological changes. Results: Analysis of variance (ANOVA) found Cortisone to have significantly (p < .05) increased glucose level in a dose dependent manner. This was however attenuated following co-administration of Ketoconazole and Vitamin E as Ketoconazole showed more potency in this ameliorating effect. Also, Cortisone was observed to significantly decrease (in dose dependent fashion), pancreatic β-cell functions, with attenuating effect seen following co-administration of Ketoconazole. Conclusion: It is recommended that caution is applied with the intake of glucocorticoids, especially in polypharmacy while treating certain ailments.

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Meloxicam induced toxicopathology studies in Wistar rats

Indian Journal of Animal Research ◽

10.18805/ijar.b-3766 ◽

2019 ◽

Author(s):

S. Pramod Bharani ◽

A. K. Naik ◽

S. C. Parija ◽

S. K. Panda

Keyword(s):

Wistar Rats ◽

Hematological Parameters ◽

Clinical Signs ◽

High Dose ◽

Dependent Manner ◽

Group Iii ◽

Group I ◽

Anti Inflammatory ◽

Group Ii ◽

Dose Dependent

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used class of drugs for treating inflammation and pain. Meloxicam has analgesic, anti-inflammatory and antipyretic properties and is a commonly used NSAID in veterinary practice. The present study was done to evaluate effect of meloxicam on toxico-pathological and hematological parameters in Wistar rats. Eighteen Wistar rats were equally divided into three groups i.e. Group I, Group II and Group III. Group I (negative control) rats received only Normal saline (0.9%) @ 1ml/kg. Group II (Low dose) received meloxicam@ 4 mg/kg B.W. and Group III (High dose) rats received meloxicam@8 mg/kg B.W. orally by gavage for 28 days. Dose-dependent clinical signs and lesions were observed after meloxicam treatment. Kidneys and liver were severely hemorrhagic at the high dose, while intestine and stomach had ulcers and erosions. Hematological values were altered after 28 days of administration. Total Erythrocyte Count (TEC), Packed Cell Volume (PCV), Haemoglobin values were decreased and TLC count was significantly increased in both doses of meloxicam treated groups in a dose-dependent manner. It was concluded that meloxicam caused GIT lesions, nephrotoxicity, hepatotoxicity and variation in the hematological parameters at selected dose and duration.

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High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽

10.3390/nu11091981 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1981 ◽

Cited By ~ 9

Author(s):

Qiufen Mo ◽

Aikun Fu ◽

Lingli Deng ◽

Minjie Zhao ◽

Yang Li ◽

...

Keyword(s):

Lipid Metabolism ◽

Systemic Inflammation ◽

Body Weight Gain ◽

High Dose ◽

Dependent Manner ◽

Glucose And Lipid Metabolism ◽

Glycerol Monolaurate ◽

Indigenous Microbiota ◽

Anti Inflammatory ◽

Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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Prolactin stimulates food intake in a dose-dependent manner

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.1.r276 ◽

1989 ◽

Vol 256 (1) ◽

pp. R276-R280 ◽

Cited By ~ 6

Author(s):

T. Gerardo-Gettens ◽

B. J. Moore ◽

J. S. Stern ◽

B. A. Horwitz

Keyword(s):

Food Intake ◽

Female Rats ◽

High Dose ◽

Dependent Manner ◽

Additional Control ◽

The Mean ◽

Ovine Prolactin ◽

Dose Dependent ◽

Medium Dose ◽

Cumulative Food Intake

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.

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Antidiarrheal Activity of Dissotis multiflora (Sm) Triana (Melastomataceae) Leaf Extract in Wistar Rats and Subacute Toxicity Evaluation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4038371 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Alian Désiré Afagnigni ◽

Maximilienne Ascension Nyegue ◽

Chantal Florentine Ndoye Foe ◽

Youchahou Njankouo Ndam ◽

Frédéric Nico Njayou ◽

...

Keyword(s):

Wistar Rats ◽

Leaf Extract ◽

Shigella Flexneri ◽

Female Rats ◽

Male Rats ◽

Dependent Manner ◽

Subacute Toxicity ◽

Antidiarrheal Activity ◽

Dose Dependent ◽

Ethanolic Leaf Extract

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days’ subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased (p<0.05) in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease (p<0.05) of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.

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Effect of the oral administration of monosodium glutamate during pregnancy and breast-feeding in the offspring of pregnant Wistar rats

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502010000100010 ◽

2010 ◽

Vol 25 (1) ◽

pp. 37-42 ◽

Cited By ~ 4

Author(s):

Vinicius von Diemen ◽

Manoel Roberto Maciel Trindade

Keyword(s):

Weight Gain ◽

Oral Administration ◽

Wistar Rats ◽

Monosodium Glutamate ◽

The Other ◽

Control Group ◽

Pregnant Rats ◽

Dependent Relation ◽

Dose Dependent

PURPOSE: Determine the effects of the MSG (monosodium glutamate) in the offspring of pregnant rats through the comparison of the weight, NAL (nasal-anal length) and IL (Index of Lee) at birth and with 21 days of life. METHODS: Pregnant Wistar rats and their offspring were divided into 3 groups: GC, G10 and G20. Each of the groups received 0%, 10% and 20% of MSG, respectively from coupling until the end of the weaning period. RESULTS: Neither weight nor NAL were different among the groups at birth. The group G20 at birth had an IL lower than the group GC (p<0,05) and with 21 days of life presented weight and NAL lower than the groups G10 and this lower than the GC (p<0,01). Otherwise the G20 at 21 days of life had the IL similar to the other two groups. The weight profit percentage from birth to the 21st day of life was lower in the G20 regarding the other two groups (p<0,01). The G20 had a NAL increase percentage from birth to the 21st day of life lower than the G10 and this lower than the GC (p<0,01). CONCLUSIONS: MSG presented a dose-dependent relation in the variables weight and NAL. It caused a decrease in the growth pattern as well as in the weight gain pattern until the 21st day of life. The IL of the group 20% had an increased in relation to the control group after 3 weeks of follow up.

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Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes

10.1101/2021.04.15.21255504 ◽

2021 ◽

Author(s):

Tobias Schmidt ◽

Robin Kahn ◽

Fredrik Kahn

Keyword(s):

Flow Cytometry ◽

Ascorbic Acid ◽

Cytokine Production ◽

In Vitro Study ◽

Surface Expression ◽

High Dose ◽

Functional Assay ◽

Dependent Manner ◽

Dose Dependent

Objective To investigate the effects of high dose ascorbic acid (AA) on monocyte polarization and cytokine production in vitro Design Experimental in vitro study of cells from healthy subjects and patients with sepsis Setting University research laboratory and academic hospital Subjects Six healthy controls and three patients with sepsis Interventions Monocytes were isolated from whole blood of healthy donors (n=6) and polarized in vitro for 48hrs using LPS or LTA. Polarization was confirmed by surface marker expression using flow cytometry. As a comparison, monocytes were also isolated from septic patients (n=3) and analyzed for polarization markers. The effect of AA on monocyte polarization was evaluated. As a functional assay, AA-treated monocytes were analyzed for cytokine production of TNF and IL-8 by intracellular staining and flow cytometry following activation with LPS or LTA. Measurements and Main Results Both LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro- (CD40 and PDL1, p<0.05) and anti-inflammatory (CD16 and CD163, p<0.05) polarization markers, with non-significant effects on CD86 and CD206. This pattern resembled, at least partly, that of monocytes from septic patients. Treatment with AA significantly inhibited the upregulation of surface expression of CD16 and CD163 (p<0.05) in a dose dependent manner, but not CD40 or PDL-1. Finally, AA attenuated LPS or LTA-induced cytokine production of IL-8 and TNF in a dose-dependent manner (both p<0.05). Conclusions AA inhibits upregulation of anti-, but not pro-inflammatory related markers in LPS or LTA polarized monocytes. Additionally, AA attenuates cytokine production from in vitro polarized monocytes, displaying functional involvement. This study provides important insight into the immunological effects of high dose AA on monocytes, and potential implications in sepsis.

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Calcitriol Exerts Prophylactic Anti-Mycobacterium Effect In A Dose-Dependent Manner

10.21203/rs.3.rs-346581/v1 ◽

2021 ◽

Author(s):

Jianguo Li ◽

Zhen Li ◽

Zefeng Gao ◽

Juan Xia ◽

Jia Cui ◽

...

Keyword(s):

Vitamin D ◽

1H Nmr ◽

Low Dose ◽

Bacterial Load ◽

High Dose ◽

Dependent Manner ◽

Prophylactic Effect ◽

Moderate Dose ◽

Metabolism Pathway ◽

Dose Dependent

Abstract Vitamin D was empirically applied for Tuberculosis (TB) treatment in the past, and is currently used as an adjuvant for TB therapy. Although an increasing pile of evidences suggests that vitamin D has no therapeutic effect against TB infection, the prophylactic effect of vitamin D in preventing TB remains largely undetermined. To experimentally valuate the potential prophylactic effect of calcitriol (the active form of vitamin D) against mycobacterium infection, we performed dose-gradient calcitriol soaking in 30-day-old zebrafish before Mycobacterium marinum (M. marinum) challenge through tail vein injection. 1H-NMR metabolomics analysis was further performed for illustration of potential mechanisms underlying the prophylactic effect of calcitriol against M. marinum. The results suggested that calcitriol exerts dose-dependent prophylactic anti-mycobacterium effects, i.e., the bacterial load and the corresponding inflammatory factors (IL-1β, TNF-α, and IFN-γ) expressions in M. marinum challenged zebrafish were reduced by low-dose (25 µg/L) or high-dose (2500 µg/L) calcitriol soaking, rather than by moderate-dose (250 µg/L) calcitriol soaking. Body weight of the M. marinum challenged zebrafish was recovered by high-dose prophylactic calcitriol soaking rather than by low-dose or moderate-dose calcitriol. The 1H-NMR metabolomic profiling identified 29 metabolites with altered abundance among the dose-gradient calcitriol groups, among which 22 metabolites were co-varied with the dose of calcitriol, the rest 7 metabolites were co-varied with the bacterial load and the inflammatory response in term of cytokine expression. Further pathway analysis indicated that the glycine, serine, and threonine metabolism pathway was the activated in both of the two metabolite groups, indicating that the pathway was altered by dose-gradient of calcitriol and was in response to M. marinum infection in zebrafish. The results of the present study suggested that the activation of glycine, serine and threonine metabolism pathway may play a potential role for the dose-dependent anti-mycobacterium effect induced by prophylactic calcitriol soaking.

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Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic β-cells

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.274.1.e38 ◽

1998 ◽

Vol 274 (1) ◽

pp. E38-E44 ◽

Cited By ~ 5

Author(s):

Eri Mukai ◽

Hitoshi Ishida ◽

Seika Kato ◽

Yoshiyuki Tsuura ◽

Shimpei Fujimoto ◽

...

Keyword(s):

Metabolic Inhibition ◽

K Channel ◽

High Dose ◽

Dependent Manner ◽

Channel Activity ◽

Β Cells ◽

Pancreatic Β Cells ◽

Patch Clamp Technique ◽

Channel Inhibition ◽

Dose Dependent

The effect of metabolic inhibition on the blocking of β-cell ATP-sensitive K+ channels (KATP channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of KATP channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 μM) of ATP applied in the inside-out mode, KATP channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose-dependent and complete KATP channel inhibition under 10 μM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATP channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K+ channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, KATPchannel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic β-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.

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