Organ toxicity of diethylnitrosamine and capsaicin in mice – in vivo study

Diethylnitrosamine (DEN) is proven to be toxic to kidneys and liver and to act as a potent carcinogen mainly in liver. Capsaicin (CAP) is an alkaloid produced by Capsicum genus plants and is considered to be a protective agent against toxicity and carcinogenicity of many substances including DEN. The aim of this study was to assess the toxicity of DEN and CAP in liver and kidneys in mice. The experiment started after two weeks of acclimatisation and was conducted according to the Czech animal welfare protection legal guidelines. At the end of the experiment the mice were sacrificed and the toxicity of DEN and CAP in liver and kidneys were analysed. The histopathological examination of the liver revealed multifocal lymphoplasmacytic reaction in parenchyma in DEN treated group. CAP used as both preventive and therapeutic agent caused reduction in number and extent of lesions. In CAP group mitotic figures were found indicating xenobiotic-induced hepatotoxicity or regenerative changes. In the kidneys DEN revealed also multifocal lymphoplasmacytic reaction that has been mitigated by CAP. Moreover histopathological observation of the kidney in DEN group has revealed granular dystrophy of the renal tubules which has not been presented in CAP treated mice. Levels of ALT, AST activity, total protein and albumin concentration was not statistically different among control and experimental groups. In this study mild protective effect of CAP on DEN-induced hepatotoxicity and nephrotoxicity was shown only in histopathological changes. The toxicity of CAP itself is questionable and further studies should be performed to verify its chemopreventive potential.

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In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

AMB Express ◽

10.1186/s13568-021-01269-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masarra M. Sakr ◽

Walid F. Elkhatib ◽

Khaled M. Aboshanab ◽

Eman M. Mantawy ◽

Mahmoud A. Yassien ◽

...

Keyword(s):

Survival Rate ◽

Murine Model ◽

Histopathological Examination ◽

Healing Process ◽

Bacterial Count ◽

Treated Group ◽

Control Group ◽

In Vivo Evaluation ◽

Systemic Spread

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

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Assessment The Efficacy of Thymol Against Toxocara Vitulorum In Experimentally Infected Rats

10.21203/rs.3.rs-827080/v1 ◽

2021 ◽

Author(s):

Shawky M Aboelhadid ◽

Sahar Abdel Aleem Abdel-Aziz

Keyword(s):

Histopathological Examination ◽

Treated Group ◽

Control Group ◽

Albino Rats ◽

Untreated Control Group ◽

Toxocara Vitulorum ◽

The Third ◽

Ifn Γ

Abstract The effect of thymol and ivermectin on the development and embryonation of Toxocara vitulorum (T. vitulorum) eggs, as well as their migration in albino rats was investigated in vitro. A total of forty male albino rats were divided into four groups for an in vivo experiment. The first group was uninfected; the second group was infected but left untreated; the third group received thymol at a dose of 40 mg/kg; and the fourth group received ivermectin (0.2 mg/kg). Thymol inhibited the development of Toxocara larvae within the eggs in vitro. Ivermectin; however, produced inconsistent results. The in vivo results indicated that the recovery rates of Toxocara larvae from the liver and lungs on day 7 post-infection were significantly lower in the thymol- or ivermectin-treated group than in the infected untreated control group. Histopathological examination demonstrated that thymol and ivermectin were effective in reducing larval load, reducing the number and size of granulomas in the absence of larvae, and improving tissue architectures. Albumin levels were significantly increased in the thymol-treated group. Nitric oxide, IL-4, and IFN- γ levels were significantly decreased in the serum of the thymol- or ivermectin-treated group. The current study concluded that thymol possessed anti-Toxocara activity in a rat model. Additionally, thymol possessed ovicidal properties and may be used as a disinfectant.

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In Vivo Evaluation of a Recombinant N-acylhomoserine Lactonase Formulated in a Hydrogel Using a Murine Model Infected With Mdr Pseudomonas Aeruginosa Clinical Isolate, CCASUP2

10.21203/rs.3.rs-209973/v1 ◽

2021 ◽

Author(s):

Masarra M. Sakr ◽

Walid F. Elkhatib ◽

Khaled Aboshanab ◽

Eman M. Mantawy ◽

Mahmoud A. Yassien ◽

...

Keyword(s):

Survival Rate ◽

Murine Model ◽

Histopathological Examination ◽

Healing Process ◽

Bacterial Count ◽

Treated Group ◽

Control Group ◽

In Vivo Evaluation ◽

Systemic Spread

Abstract Failure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

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Cytotoxicity, Anti-diabetic, and hepato-protective potential of Ajuga bracteosa-conjugated silver nanoparticles in Balb/c mice

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210421101837 ◽

2021 ◽

Vol 22 ◽

Author(s):

Sadia Nazer ◽

Saiqa Andleeb ◽

Shaukat Ali ◽

Nazia Gulzar ◽

Abida Raza ◽

...

Keyword(s):

Silver Nanoparticles ◽

Histopathological Examination ◽

Treated Group ◽

Functional Markers ◽

Protective Potential ◽

Liver And Kidney ◽

Histopathological Studies ◽

Green Synthesized Silver Nanoparticles

Background: Ajuga bracteosa is a traditional herb used against various diseases. Objective: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). Methods: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. Results: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepato-protective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity. Conclusion: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepato-protective phytoconstituents which could be used in the prevention of diseases.

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In Vivo Wound Healing Activity of Spirulina platensis

Phytothérapie ◽

10.3166/phyto-2018-0097 ◽

2019 ◽

Vol 18 (1) ◽

pp. 06-16

Author(s):

R. Seghiri ◽

A. Essamri

Keyword(s):

Wound Healing ◽

Spirulina Platensis ◽

Therapeutic Agent ◽

Conventional Medicine ◽

Folk Medicine ◽

Chemical Burns ◽

Amount Of Substance ◽

Test Population ◽

Wound Healing Activity

Spirulina is a microalga used in traditional folk medicine in Morocco for the treatment of various health disorders. The wound healing activity of Moroccan Spirulina is unknown. In the current study, aqueous extracts of Spirulina platensis were investigated for acute toxicity and wound healing activity in Swiss Albino mice and White New Zealand rabbits, respectively. The LD50 (amount of substance required to kill 50% of the test population) of the microalga was greater than 5,000 mg/kg. Healing after application of the same amount of ointment on differently induced (mechanical, chemical, and thermal) wounds was about the same, over five weeks. Aqueous extract had remarkable healing activity on rabbits’ skin, possessing significantly greater healing effect for mechanical and chemical burns than controls. Moreover, the hair growing time was faster in treated groups; Spirulina-treated groups did not show any contamination with microbes compared to others. This study affirms that Spirulina platensis can be considered as a potential therapeutic agent for wound healing not only as a complementary medicine but also in conventional medicine.

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The effect of dexamethasone on mucosal immunity of uterine tissue during pregnancy in rat

Mansoura Veterinary Medical Journal ◽

10.35943/mvmj.2019.01.1013 ◽

2019 ◽

Vol 20 (1) ◽

pp. 75-84

Keyword(s):

Early Pregnancy ◽

Histopathological Examination ◽

Early Period ◽

Interleukin 10 ◽

Treated Group ◽

Female Rats ◽

Male Rats ◽

Mrna Levels ◽

Uterine Tissue ◽

Leukocytic Infiltration

Disturbances in early pregnancy immunity affect embryo development, endometrial receptivity, placental development, fetal growth and lead to subfertility, dexamethasone is a synthetic glucocorticoid used for treatment of various complications. Immune cells and cytokines were examined during the early pregnancy in twenty-four female rats and six male rats for mating. Rats were grouped into two group control and dexamethasone treated by a dose of 50µgm/kgm body weight daily starting from one week before mating and persisted for one week after pregnancy. Blood samples were collected from each rat at 5hrs and at 1,3,7 day of pregnancy. Extracted RNA was subjected to real time PCR to determine mRNA levels for immune related genes interleukin1a(IL1A) and interleukin 10(IL10). Histopathological examination was done to uterus in order to detect leukocyte infiltration in uterine tissue. Results showed that significant increase in white blood cell count mainly eosinophil at 5hrs and lymphocyte at three and seven day of pregnancy of dexamethasone treated group. Moreover, TNF, C-reactive protein and progesterone were increased mainly at seven day of pregnancy of dexamethasone treated group. Similarly, interleukin 1alpha and interleukin 10 significantly increased at 5hrs and one day of pregnancy of dexamethasone treated group. In contrast, serum levels of total antioxidant capacity and estrogen were decreased significantly at 5hrs and seven day in dexamethasone treated group. Histopathological examination of uterus revealed leukocytic infiltration especially neutrophil and few eosinophils at five hours and one day of gestation then eosinophil become absent at 3day and seven day of dexamethasone group. Epithelial height and uterine gland diameter significantly increased at 5hrs, three day and seven days of gestation of dexamethasone treated group. The present investigation demonstrated that using of dexamethasone by dose of 50µgm/kgm during early pregnancy had a conflicting impact on some immune cytokines and parameters and may reflect a harmful response of immune system toward early period of pregnancy

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Identification of 2-Fluoropalmitic Acid as a Potential Therapeutic Agent Against Glioblastoma

Current Pharmaceutical Design ◽

10.2174/1381612826666200429092742 ◽

2020 ◽

Vol 26 (36) ◽

pp. 4675-4684 ◽

Cited By ~ 1

Author(s):

Shabierjiang Jiapaer ◽

Takuya Furuta ◽

Yu Dong ◽

Tomohiro Kitabayashi ◽

Hemragul Sabit ◽

...

Keyword(s):

Combination Therapy ◽

Drug Screening ◽

Therapeutic Agent ◽

Gelatin Zymography ◽

Therapeutic Agents ◽

Drug Candidate ◽

Potential Therapeutic Agent ◽

Sphere Formation ◽

Improve Patient

Background: Glioblastomas (GBMs) are aggressive malignant brain tumors. Although chemotherapy with temozolomide (TMZ) can extend patient survival, most patients eventually demonstrate resistance. Therefore, novel therapeutic agents that overcome TMZ chemoresistance are required to improve patient outcomes. Purpose: Drug screening is an efficient method to find new therapeutic agents from existing drugs. In this study, we explored a novel anti-glioma agent by drug screening and analyzed its function with respect to GBM treatment for future clinical applications. Methods: Drug libraries containing 1,301 diverse chemical compounds were screened against two glioma stem cell (GSC) lines for drug candidate selection. The effect of selected agents on GSCs and glioma was estimated through viability, proliferation, sphere formation, and invasion assays. Combination therapy was performed to assess its ability to enhance TMZ cytotoxicity against GBM. To clarify the mechanism of action, we performed methylation-specific polymerase chain reaction, gelatin zymography, and western blot analysis. Results: The acyl-CoA synthetase inhibitor 2-fluoropalmitic acid (2-FPA) was selected as a candidate anti-glioma agent. 2-FPA suppressed the viability and stem-like phenotype of GSCs. It also inhibited proliferation and invasion of glioma cell lines. Combination therapy of 2-FPA with TMZ synergistically enhanced the efficacy of TMZ. 2-FPA suppressed the expression of phosphor-ERK, CD133, and SOX-2; reduced MMP-2 activity; and increased methylation of the MGMT promoter. Conclusion: 2-FPA was identified as a potential therapeutic agent against GBM. To extend these findings, physiological studies are required to examine the efficacy of 2-FPA against GBM in vivo.

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Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666201230113018 ◽

2020 ◽

Vol 21 ◽

Author(s):

Hana M. Hammad ◽

Amer Imraish ◽

Maysa Al-Hussaini ◽

Malek Zihlif ◽

Amani A. Harb ◽

...

Keyword(s):

Wound Healing ◽

Rural Communities ◽

Ex Vivo ◽

Ethanol Extract ◽

Aortic Ring ◽

Treated Group ◽

Control Group ◽

Dependent Manner ◽

Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

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Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

The International Journal of Lower Extremity Wounds ◽

10.1177/15347346211002144 ◽

2021 ◽

pp. 153473462110021

Author(s):

Joon M. Jung ◽

Hae K. Yoon ◽

Chang J. Jung ◽

Soo Y. Jo ◽

Sang G. Hwang ◽

...

Keyword(s):

Wound Healing ◽

Plasma Treatment ◽

Cold Plasma ◽

Smooth Muscle Actin ◽

Treated Group ◽

Control Group ◽

Alpha Smooth Muscle Actin ◽

Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

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Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics13040444 ◽

2021 ◽

Vol 13 (4) ◽

pp. 444

Author(s):

Alaa Mahran ◽

Sayed Ismail ◽

Ayat A. Allam

Keyword(s):

Triamcinolone Acetonide ◽

Delivery System ◽

Histopathological Examination ◽

Rabbit Model ◽

Subconjunctival Injection ◽

In Vivo Evaluation ◽

Ternary Phase Diagrams ◽

Ophthalmic Delivery

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

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