In vivo evaluation of inorganic nanoparticle complexes against CCL4 induced hepatotoxicity

2021 ◽  
Vol 18 ◽  
Author(s):  
Rabia Tabbasam ◽  
Sana Khursid ◽  
Yasmeen Ishaq ◽  
Arif Malik

Background: Combination of different chemotherapy drugs and nanoparticles as a carrier have shown promising delivery system in cancer treatment. Doxorubicin is considered as a potent anticancer drug. However, it’s off target activities and possible side effects, make its use limited. Recently, in the field of nanomedicine, different nanoconjugates have been developed as a unique platform for the delivery of therapeutic drugs. Objective: The aim of present study was to evaluate the best possible combination for efficient delivery of DOX with combination of gold, silver and zinc oxide nanoparticles to target site against carbon tetrachloride induced rat hepatotoxicity. Methodology: Effect of different conjugates administrated for 14 consecutive days was evaluated. Results: In comparison to DOX, Au:DOX, ZnoO:DOX and Ag:DOX showed less sign of liver fibrosis as evaluated by serum enzymes and histo-pathological analysis. However, among all the conjugates, Ag: DOX conjugate showed most significant results. The serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase values were (111.2 ± 38.21, 323.2 ± 46.88 and 303.6 ± 73.80 respectively) very close to control group (72.2 ± 19.41, 368 ± 59.78 and 259.4 ± 61.54 respectively). Conclusion: Our results demonstrated that Ag: DOX may exhibit hepato-protective activity against CCl4 induced liver damage.

2018 ◽  
Vol 34 (11) ◽  
pp. 753-763 ◽  
Author(s):  
Zulfia Hussain ◽  
Junaid Ali Khan ◽  
Hafeez Anwar ◽  
Naila Andleeb ◽  
Sehrish Murtaza ◽  
...  

Zinc oxide nanoparticles (ZnONPs) are being used extensively in manufacturing skin lotions and food products and in various biological and pharmaceutical industries because of their immunomodulatory and antimicrobial properties. In this study, ZnONPs were synthesized by a precipitation method and characterized by X-ray diffraction (XRD) techniques, scanning electron microscopy (SEM), and ultraviolet–visible spectroscopy to investigate their structural, morphological, and optical properties. For in vivo evaluation, 40 healthy albino mice were randomly allocated to four equal groups among which the first one was the control group, while the second, third, and fourth were treated with carbon tetrachloride (CCl4), a blend of CCl4 and ZnONPs, and ZnONPs alone, respectively, for 21 days. The XRD analysis confirmed hexagonal wurtzite type structures having an average crystallite size of 41.54 nm. The morphology of ZnONPs analyzed through SEM showed uniform distribution of the grains and shape of the synthesized oxide. The energy band gap of the ZnONPs was found to be 3.498 eV. Hepatic and renal damage following CCl4 administration was apparent after 14 days and was increased at the 21st day, showing nodular fibrotic masses in the liver and bumpy surfaces in the kidney as observed by gross and histological examination. Coadministration of ZnONPs (15 mg/kg b.w. intragastrically 5 days a week) significantly prevented the CCl4-dependent increases in alanine transaminase, aspartate transaminase, creatinine, and urea levels, suggesting a protective potential of ZnONPs.


AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masarra M. Sakr ◽  
Walid F. Elkhatib ◽  
Khaled M. Aboshanab ◽  
Eman M. Mantawy ◽  
Mahmoud A. Yassien ◽  
...  

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.


2017 ◽  
Vol 43 (10) ◽  
pp. 1610-1618 ◽  
Author(s):  
Jianmei Zhang ◽  
Yunpeng He ◽  
Jianqi Jiang ◽  
Meng Li ◽  
Chenhao Jin ◽  
...  

2021 ◽  
pp. 030157422110373
Author(s):  
Prasad Chitra ◽  
GS Prashantha ◽  
Arun Rao ◽  
Harshvardhan S Jois

Introduction: Fluoride agents to prevent white spot lesions are used often during orthodontic treatment. The beneficial effects of fluoride, when consumed within permissible limits on dental structures, are well known. Their implications on underlying biological tissues, however, are unknown. Mouthwashes and dentifrices with fluorides are associated with metal ion release into the mouth with possible cell genotoxicity. Since these cariostatic agents are frequently used during orthodontic therapy, a deeper understanding of the effects of fluoride on oral tissues was considered necessary. Methodology: Three groups of patients (30 each)—group 1 (untreated controls), group 2 (non-fluoridated), and group 3 (Fluoridated) were analyzed. Patients in groups 2 and 3 were bonded with the same bracket prescription and treated with similar archwire sequences. Buccal mucosal cells at 4 specific time periods (before treatment, 1 week, 30 days, and 6 months) were collected, using a wooden tongue depressor, and assessed for any nuclear abnormalities. Comparisons of changes were made with an untreated control group and also between the non-fluoridated and fluoridated groups. Relevant conclusions were drawn after analysis of the results. Results: Greater number of nuclei were observed at the 30-day time interval in the fluoridated group, which was statistically significant at P < .001. Conclusion: Use of fluoridated oral hygiene products in patients undergoing fixed orthodontic treatment with NiTi archwires could increase the risk of micronuclei formation in buccal mucosal cells.


2013 ◽  
Vol 41 (04) ◽  
pp. 865-885 ◽  
Author(s):  
Sheng-Chi Lee ◽  
Chin-Chuan Tsai ◽  
Chun-Hsu Yao ◽  
Yuan-Man Hsu ◽  
Yueh-Sheng Chen ◽  
...  

The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 μg/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 μg/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 μg/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I–II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 μg/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury.


2021 ◽  
Author(s):  
Satya V.V.N. Kothapalli ◽  
Tammie L. Benzinger ◽  
Andrew. J. Aschenbrenner ◽  
Richard. J. Perrin ◽  
Charles. F. Hildebolt ◽  
...  

AbstractBackgroundCurrently, brain tissue atrophy serves as in vivo MRI biomarker of neurodegeneration in Alzheimer Disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuronal loss prior to detectable atrophy in MRI is essential for early AD diagnosis.ObjectiveTo apply a recently developed quantitative Gradient Recalled Echo (qGRE) MRI technique for in vivo evaluation of neuronal loss in human hippocampus.MethodsSeventy participants were recruited from the Knight Alzheimer Disease Research Center, representing three groups: Healthy controls [Clinical Dementia Rating® (CDR®)=0, amyloid β (Aβ)-negative), n=34]; Preclinical AD (CDR=0, Aβ-positive, n=19); and mild AD (CDR=0.5 or 1, Aβ-positive, n=17).ResultsIn hippocampal tissue, qGRE identified two types of regions: one, practically devoid of neurons, we designate as “Dark Matter”, the other, with relatively preserved neurons - “Viable Tissue”. Data showed a greater loss of neurons than defined by atrophy in the mild AD group compared with the healthy control group - neuronal loss ranged between 31% and 43% while volume loss ranged only between 10% and 19%. The concept of Dark Matter was confirmed with histopathological study of one participant who underwent in vivo qGRE 14 months prior to expiration.Conclusionin vivo qGRE method identifies neuronal loss that is associated with impaired AD-related cognition but is not recognized by MRI measurements of tissue atrophy, therefore providing new biomarkers for early AD detection.


2019 ◽  
Vol 20 (12) ◽  
Author(s):  
AFAF BENHOUDA ◽  
DJAHIDA BENHOUDA ◽  
MASSINISSA YAHIA

Abstract. Benhouda A, Benhouda D, Yahia M. 2019. In vivo evaluation of anticryptosporidiosis activity of the methanolic extract of the plant Umbilicus rupestris. Biodiversitas 20: 3478-3483. Umbilicus rupestris (Crassulaceae) is a medicinal plant used in general traditional medicine to cure inflammation and irritation of the skin. The present research is aimed to evaluate the antiparasitic activity of the methanolic extract of the plant URMeOH of U. rupestris against the Cryptosporidium infection in immunocompetent and immunosuppressed rats experimentally infected. Twenty-one female rats were divided into two groups. Control group (group I) and experimental group (Group II). The group I was further divided into three equal groups (normal group infected and immunosuppressed infected group). The experimental group was divided into two immunosuppressed and four equal groups and two immunocompetent infected. Cryptosporidium oocysts were isolated from bovine species stools and used to infect rats. Experimental subgroups received URMeOH two as dose 100mg/kg b.w. and 200 mg/kg b.w. and continued until 15 days. Two weeks after the administration of URMeOH, feces of rats were examined for the detection of Cryptosporidium oocysts by Ziehl-Neelsen and immunofluorescence techniques, the animals were sacrificed; their small intestines were processed and examined for the detection of pathological lesions after histopathological study. In addition, the activity of myeloperoxidase (MPO) was measured in sections of the jejunum. Concerned the results, we observed a statistically significant (P<0.001) increase in the number of oocysts of Cryptosporidium in the stool for sub infected immunosuppressed groups and an increase of MPO activity compared to the corresponding subgroups immunocompetent subgroups. The URMeOH could remove Cryptosporidium oocysts from feces and intestinal sections subgroup infected immunocompetent rats receiving URMeOH. Moreover, the oocysts were significantly reduced in all other subgroups experimental infected compared to infected control subgroups. Intestinal sections in all subgroups received URMeOH revealed a more or less normal architecture. In addition, the reduction of MPO activity level was also detected in all experimental subgroups.


2021 ◽  
Author(s):  
Teresa Savarese ◽  
Andrea Abate ◽  
Ram Manohar Basnet ◽  
Luigi Lorini ◽  
Cristina Gurizzan ◽  
...  

Abstract Purpose Adenoid cystic carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse. When relapsing, ACC has an indolent but relentless behaviour, thus leading to a poor long-term prognosis. The treatment of choice of relapsing ACC remains surgery followed by radiotherapy, whenever feasible. Therapeutic weapons are limited to systemic drugs. The most widely used chemotherapy regimen is the combination of cisplatin and doxorubicin, however with low response rate and not long lasting; there is also a lack of alternatives for second line therapies in case of disease progression. Therefore, a more comprehensive strategy aimed at identifying at preclinical level the most promising drugs or combination is clearly needed. Methods In this study, the cytotoxic effects of two standard chemotherapy drugs, cisplatin and doxorubicin, and of five targeted therapy-drugs was tested in vitro, on an h-TERT immortalized ACC cell line. The same drugs were also tested in vivo, on zebrafish embryos with ACC tumoral cell xenograft. Then, combinations of one standard chemotherapy drug plus one targeted therapy drug were also evaluated, in order to find the best treatment strategy for ACC. Results Data obtained demonstrated that both vorinostat and olaparib significantly increased the standard chemotherapy cytotoxic effects, suggesting new interesting therapeutic options for ACC. Conclusion Data obtained in the present study provide valid new therapeutic strategies for ACC to be translated in a prospective clinical trial.


2020 ◽  
Author(s):  
Svetlana Bezukladova ◽  
Jouni Tuisku ◽  
Markus Matilainen ◽  
Anna Vuorimaa ◽  
Marjo Nylund ◽  
...  

Objective: To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter damage in multiple sclerosis (MS) brain, and to examine their association with clinical disability. Methods: 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [11C](R)-PK11195. TSPO-binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated within the whole normal appearing white matter (NAWM) and segmented NAWM regions appearing normal in conventional MRI. 55 MS patients and 15 healthy controls were examined. Results: Microstructural damage was observed in the NAWM of MS brain. DTI parameters of MS patients were significantly altered in the NAWM, when compared to an age- and sex-matched healthy control group: mean FA was decreased, and MD, AD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM (p<0.05 for all correlations; p<0.01 for RD in the temporal NAWM). Both compromised WM integrity and increased microglial activation in the NAWM correlated significantly with higher clinical disability measured with expanded disability status scale (EDSS). Conclusions: Widespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI imaging allows in vivo evaluation of widespread MS pathology not visible using conventional MRI.


2019 ◽  
Vol 8 (9) ◽  
pp. 1486 ◽  
Author(s):  
Barbara De Angelis ◽  
Margarida Fernandes Lopes Morais D’Autilio ◽  
Fabrizio Orlandi ◽  
Giampiero Pepe ◽  
Simone Garcovich ◽  
...  

Chronic ulcers are characterized by loss of substance without a normal tendency towards spontaneous healing. The Wound Bed Preparation Guideline advises that after diagnosis, the expert should correct the biological state of the ulcer micro-environment based on TIME principles (Tissue, Infection, Moisture balance, Epidermal). There are many ways to treat such ulcers, for example through use of advanced dressings, negative pressure, surgical toilets, dermal substitutes, autologous skin grafting, and free or local flaps. In vitro and in vivo pre-clinical models hold widely acknowledged potential yet complex limitations. Tissue bioengineering could be an ideal approach to foster innovative strategies in wound healing. Our observational study reports on an in vitro and in vivo evaluation of a bio-functionalized scaffold composed of platelet-rich plasma (PRP) and hyaluronic acid (HA) used in 182 patients affected by chronic ulcers (diabetic and vascular), comparing the results with a control group of 182 patients treated with traditional dressings (HA alone). After 30 days the patients who had undergone the combined treatment (PRP + HA), showed 96.8% ± 1.5% re-epithelialization, as compared to 78.4% ± 4.4% in the control group (HA only). Within 80 days, they had 98.4% ± 1.3% re-epithelialization as compared to 87.8% ± 4.1% in the control group (HA only; p < 0.05). No local recurrence was observed during the follow-up period. PRP + HA treatment showed stronger regenerative potential in terms of epidermal proliferation and dermal renewal compared with HA alone.


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