scholarly journals Detection of Toxic Effects of Clostridial Crude Toxin in Experimental Rats

2013 ◽  
Vol 21 (1-2) ◽  
pp. 65-72
Author(s):  
MS Miah ◽  
M Asaduzzaman ◽  
A Siddika ◽  
N Popy ◽  
MA Sufian ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Inflammatory Cells ◽  
Toxic Effects ◽  
Fatty Change ◽  
Hair Coat ◽  
Crude Toxin ◽  
Leukocytic Infiltration ◽  
Dose Dependent ◽  
Lung And Kidney ◽  
Different Doses

The present study was conducted for the detection of toxic effects of clostridial crude toxin in experimental rats. The crude toxin of Clostridium perfringens was prepared and the rats were injected intraperitoneally (IP) 0.5 ml, 1.0 ml and 2.0 ml of crude toxin. The rats were observed for 24 hrs. The crude toxin inoculated rats showed the dose dependent clinical signs; depression, rough hair coat, respiratory distress, diarrhea and rapid heart beats, whereas PBS inoculated rats did not show any clinical sings. Necropsy changes were variable however, highly dilated and distended whole intestine with blood stained semifluid contents and gas along with congestion in all the affected rats were found dose dependently. Liver, lung and kidney were congested, hemorrhagic and swollen. More or less hydrothorax was seen during the postmortem of all affected rats. The peritoneal fat was frequently congested in all affected rats. Histopathological changes in intestine (0.5 ml inoculated rats) involved congestion, slightly swollen goblet cells and hemorrhages. The most severe lesions comprised of profuse hemorrhages in the mucosa and submucosa with complete necrosis, desquamation and intense leukocytic infiltration in 2 ml inoculated rats. Affected liver (1 ml inoculated rats) exhibited engorgement of central veins, sinusoidal spaces with blood and fatty change. The hepatocytes revealed swelling, granulation and vacuolation of cell cytoplasm, extensive hemorrhage and congestion were seen in 2 ml toxin inoculated rats. Congestion and sometimes extravasation were observed in the subepicardial region of heart. The myocardium revealed mild degenerative changes in the form of granularity of myocardial fiber. In lungs there was congestion, hemorrhage and leukocytes infiltration in the interstitial spaces around the bronchioles in both 1 and 2 ml toxin inoculated rats. Affected kidneys of different doses of crude toxin showed hemorrhage, congestion and inflammatory cells dose dependently. From the above findings, it may be concluded that clostridial crude toxin induced clinical signs, gross and histopathological lesions dose dependently in experimental rats.DOI: http://dx.doi.org/10.3329/pa.v21i1-2.16753 Progress. Agric. 21(1 & 2): 65 - 72, 2010

Histopathological changes in the liver and kidney tissues of Wistar albino rat exposed to fenitrothion

2008 ◽  
Vol 24 (9) ◽  
pp. 581-586 ◽  
Author(s):  
S Afshar ◽  
AA Farshid ◽  
R Heidari ◽  
M Ilkhanipour
Keyword(s):  
Control Group ◽  
Histopathological Changes ◽  
Albino Rat ◽  
Hydropic Degeneration ◽  
Leukocytic Infiltration ◽  
Male Wistar Rats ◽  
Liver And Kidney ◽  
Dose Dependent ◽  
Significant Injury ◽  
Different Doses

The aim of this study was to investigate the dose-related effects of fenitrothion (FNT) on the liver and kidney. The study was conducted on 8-week-old male Wistar rats that were divided into four groups (three experimental groups and one control group) and were treated orally with different doses (25, 50, 100 mg/kg) of FNT for 28 consecutive days. After treatment, the rats were anesthetized with ether and liver and kidney samples were taken for histological studies. The results showed that the histopathological changes in the liver were mainly represented by parenchymatous degeneration of hepatocytes with mild necrosis, leukocytic infiltration in the portal area, severe congestion, and hemorrhage. These changes were dose dependent. Marked tubular dilation, hydropic degeneration in tubular epithelium, moderate congestion, and hemorrhage in the cortical and medulla part of the kidney were recorded. Histopathologic examination of the liver and kidney indicated a significant injury only in rats receiving 100 mg/kg FNT.

Ovalbumin/lipopolysaccharide induced vasculitis in rats: a new predictive model

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Vandana R. Thakur ◽  
Anita A. Mehta
Keyword(s):  
Inflammatory Cytokines ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Tnf Α ◽  
Disease Induction ◽  
Dose Dependent ◽  
Different Doses

Abstract Objectives Currently, there are several animal models for vasculitis. Ovalbumin and lipopolysaccharide (OVA, LPS) are well established for causing inflammation and used as an adjunct in the vasculitis induction. However, to date, none has established the effect of OVA and LPS in disease induction. Therefore, in the present study, an attempt has been made to develop a new animal model for vasculitis using OVA/LPS in rats. Methods A total of 42 Wistar rats were divided randomly into seven groups (n=6/group), normal control, and three different doses (0.5, 1, and 5 mg/kg) of OVA and LPS treated groups. Half of the rats in each group received only intraperitoneal sensitization, while the remaining half rats were additionally subjected to a one-week intranasal challenge. Results Results showed that both OVA/LPS in their respective groups have significantly increased circulating inflammatory cells, C-reactive protein (CRP), Inflammatory cytokines (IL-1β, IL-6, TNF-α), Kidney damage markers (BUN, Creatinine), and liver function enzymes (AST, ALT) in a dose-dependent manner. Conclusions OVA/LPS induced vascular inflammation in a dose-dependent manner. However, the higher (5 mg/kg) dose of ovalbumin and lipopolysaccharide has contributed to severe vascular inflammation through increasing inflammatory cytokines. These findings suggest that OVA/LPS may contribute as a possible model for vasculitis in rats.

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

scholarly journals Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

2021 ◽  
Vol 73 (2) ◽  
pp. 323-345
Author(s):  
Samuel Kohtala
Keyword(s):  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Post Traumatic Stress ◽  
Active Metabolites ◽  
The Past ◽  
Antidepressant Effects ◽  
Post Traumatic ◽  
Pharmacologically Active ◽  
Dose Dependent ◽  
Different Doses

AbstractOver the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.

scholarly journals Safety Study on Ketoprofen in Pigs: Evaluating the Effects of Different Dosing and Treatment Scheme on Hematological, Hepatic, and Renal Parameters

2021 ◽  
Vol 8 (2) ◽  
pp. 30
Author(s):  
Luis Emilio Fazzio ◽  
Santiago José Raggio ◽  
Juan Facundo Romero ◽  
Juver Membrebe ◽  
Antonio Humberto Hamad Minervino
Keyword(s):  
Body Condition Score ◽  
Clinical Signs ◽  
Study Groups ◽  
Control Group ◽  
Safety Study ◽  
Treatment Groups ◽  
Treatment Scheme ◽  
Condition Score ◽  
Biochemical Evaluation ◽  
Different Doses

A safety study on ketoprofen 10% was carried out on pigs using a different dosing and treatment scheme. Forty healthy crossbreed pigs with similar age, weight, and body condition score were distributed into five treatment groups. The pigs were intramuscularly injected once with different doses of ketoprofen: 3 mg/kg (group 1X), 6 mg/kg (group 2X), 9 mg/kg (group 3X). In addition, the 3 mg/kg dosis was administered on three consecutive days (group 1X ext.). Intramuscular injections of saline solution were used in control group (CTL). The pigs were clinically examined throughout the trial and blood samples were taken for hematological and biochemical evaluation on days −4 (before treatment), +3, +7, and +14 (the end of the trial). Any unusual behaviour or clinical signs were reported as potential toxic effects of ketoprofen. Serum measurements showed that none of the ketoprofen doses produced changes in renal or hepatic biochemical parameters, liver enzymes, or total bilirubin. Likewise, hematological assessment indicated no altered parameters or hematocrit percentage in the study groups. These results demonstrate that ketoprofen has no adverse effects in pigs when the doses and scheme evaluated in this study are applied.

scholarly journals Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anton Lindberg ◽  
Ryosuke Arakawa ◽  
Tsuyoshi Nogami ◽  
Sangram Nag ◽  
Magnus Schou ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Specific Binding ◽  
Occipital Cortex ◽  
Intrinsic Activity ◽  
High Affinity ◽  
G Protein Coupled ◽  
Dose Dependent ◽  
The Brain ◽  
Agonist Affinity States ◽  
Different Doses

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.

scholarly journals CTRP9 protects against MIA-induced inflammation and knee cartilage damage by deactivating the MAPK/NF-κB pathway in rats with osteoarthritis

2020 ◽  
Vol 15 (1) ◽  
pp. 971-980
Author(s):  
Shicheng Zheng ◽  
Jing Ren ◽  
Sihai Gong ◽  
Feng Qiao ◽  
Jinlong He
Keyword(s):  
Synovial Fluid ◽  
Nuclear Factor Kappa B ◽  
Cartilage Damage ◽  
Cartilage Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nuclear Factor ◽  
Knee Cartilage ◽  
Monosodium Iodoacetate ◽  
Dose Dependent ◽  
Different Doses

AbstractC1q/TNF-related protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to protect against inflammation-related diseases. However, its role in regulating osteoarthritis (OA) has not been fully elucidated. First, a rat model of OA was generated. Furthermore, rats with OA were injected with different doses of recombinant CTRP9 protein (rCTRP9), and the knee cartilage damage was evaluated. Finally, the phosphorylation of p38 and the secretion of matrix metalloproteinases (MMPs) were detected by Western blotting and enzyme-linked immunosorbent assay. Results revealed that CTRP9 was highly expressed in adipose tissue, followed by skeletal muscle and cartilage tissue, and less expressed in liver, kidney and lung. Moreover, the expression of CTRP9 significantly decreased in the monosodium iodoacetate (MIA) group in the knee cartilage and knee synovial fluid, and the contents of interleukin-1β (IL-1β) and IL-6 significantly increased in knee synovial fluid. In addition, rCTRP9 alleviated MIA-induced inflammation, oxidative stress and knee cartilage damage in a dose-dependent way. In addition, rCTRP9 could attenuate the expression of p38MAPK and p-p38 and suppress the expression of nuclear factor-kappa B (NF-κB), p65 and MMPs. Collectively, the results of the present study suggested that CTRP9 alleviates the inflammation of MIA-induced OA through deactivating p38MAPK and NF-κB signaling pathways in rats.

scholarly journals Pyrrolizidine Alkaloid-Induced Hepatotoxicity Associated with the Formation of Reactive Metabolite-Derived Pyrrole–Protein Adducts

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 723
Author(s):  
Jiang Ma ◽  
Mi Li ◽  
Na Li ◽  
Wood Yee Chan ◽  
Ge Lin
Keyword(s):  
Natural Products ◽  
Pyrrolizidine Alkaloids ◽  
Pyrrolizidine Alkaloid ◽  
Protein Adducts ◽  
Dependent Manner ◽  
Histological Changes ◽  
Histological Results ◽  
Dose Dependent ◽  
Different Doses ◽  
Alt Activity

Pyrrolizidine alkaloids (PAs) with 1,2-unsaturated necine base are hepatotoxic phytotoxins. Acute PA intoxication is initiated by the formation of adducts between PA-derived reactive pyrrolic metabolites with cellular proteins. The present study aimed to investigate the correlation between the formation of hepatic pyrrole–protein adducts and occurrence of PA-induced liver injury (PA-ILI), and to further explore the use of such adducts for rapidly screening the hepatotoxic potency of natural products which contain PAs. Aqueous extracts of Crotalaria sessiliflora (containing one PA: monocrotaline) and Gynura japonica (containing two PAs: senecionine and seneciphylline) were orally administered to rats at different doses for 24 h to investigate PA-ILI. Serum alanine aminotransferase (ALT) activity, hepatic glutathione (GSH) level, and liver histological changes of the treated rats were evaluated to assess the severity of PA-ILI. The levels of pyrrole–protein adducts formed in the rats’ livers were determined by a well-established spectrophotometric method. The biological and histological results showed a dose-dependent hepatotoxicity with significantly different toxic severity among groups of rats treated with herbal extracts containing different PAs. Both serum ALT activity and the amount of hepatic pyrrole–protein adducts increased in a dose-dependent manner. Moreover, the elevation of ALT activity correlated well with the formation of hepatic pyrrole–protein adducts, regardless of the structures of different PAs. The findings revealed that the formation of hepatic pyrrole–protein adducts—which directly correlated with the elevation of serum ALT activity—was a common insult leading to PA-ILI, suggesting a potential for using pyrrole–protein adducts to screen hepatotoxicity and rank PA-containing natural products, which generally contain multiple PAs with different structures.

scholarly journals Effect of Vernonia amygdalina on phospholipase activity from Naja Mossambica (Cobra)

2021 ◽  
Vol 6 (3) ◽  
pp. 053-060
Author(s):  
Abdullahi Abdulkakdir ◽  
Omeremime Elizabeth Dania ◽  
Bala Alkali Mohammed ◽  
Yahaya Abubakar Mohammed ◽  
Maimuna Bello Umar ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Membrane Integrity ◽  
Maximal Velocity ◽  
Vernonia Amygdalina ◽  
Phospholipase Activity ◽  
Bioactive Agents ◽  
Dose Dependent ◽  
Hydrolysis Of ◽  
Menten Constant ◽  
Different Doses

Background: Phospholipases are one of the numerous enzymes found in the Naja mossambica venom. They play a major role in snakebite envenomation, and also responsible for the hydrolysis of a phospholipid, disrupting the membrane integrity. In this study, we evaluated the effect of Vernonia amygdalina on Phospholipase activity from Naja mossambica (Cobra) Results: Partially purified phospholipase had maximal velocity (Vmax) and Michaelis Menten constant (Km) of 7.6 × 10-5 mol/min and 1.7mg/ml, while the crude phospholipase had Vmax and Km of 9.4 × 10-5mol/min and 2.5mg/ml respectively. Inhibition study of aqueous extracts of Vernonia amygdalina leaf shows that the extract is a potent inhibitor of crude phospholipase in a dose-dependent pattern. The different doses of extract 15 %, 10 % and 5% produced percentage inhibition of 74.04 %, 78.6 % and 86.63% respectively. The kinetic binding constant (Ki) values of crude phospholipase for different concentrations of extracts 5%, 10% and 15% were 0.21mg/ml, 0.29mg/ml and 0.39mg/ml, while the partially purified phospholipase for different concentrations of extracts 5%, 10% and 15% were were 0.48mg/ml, 0.42mg/ml and 0.41mg/ml respectively. It can be deduced from the results that the extract inhibits the phospholipase activity in an uncompetitive manner. Conclusion: Aqueous extract of Vernonia amygdalina leaves may contain some bioactive agents that could serve as potent inhibitors of phospholipase from Naja mossambica venom.

scholarly journals Therapeutic Potential of Human Neutrophil Peptide 1 against Experimental Tuberculosis

2001 ◽  
Vol 45 (2) ◽  
pp. 639-640 ◽  
Author(s):  
Sudhir Sharma ◽  
Indu Verma ◽  
G. K. Khuller
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Human Neutrophil ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Therapeutic Activity ◽  
Experimental Tuberculosis ◽  
Dose Dependent ◽  
Different Doses ◽  
Human Neutrophil Peptide

ABSTRACT The therapeutic efficacy of human neutrophil peptide 1 (HNP-1) against experimental tuberculosis in mice on the basis of numbers of CFU has been examined. Mice infected with 1.5 × 104CFU of Mycobacterium tuberculosisH37Rv and treated with different doses of HNP-1 injected subcutaneously exhibited significant clearance of bacilli from lungs, livers, and spleens. There were time- and dose-dependent decreases in the bacillary load in lungs, livers, and spleens of the HNP-1-treated animals compared to that in controls (untreated animals). These observations strongly suggest the therapeutic activity of HNP-1 against tuberculosis.

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