scholarly journals Preliminary screening of the possible protective effect of Moroccan propolis against chromium-induced nephrotoxicity in animal model

2020 ◽  
Vol 13 (7) ◽  
pp. 1327-1333
Author(s):  
Soukaina El-Guendouz ◽  
Soumia Zizi ◽  
Youssef Elamine ◽  
Badiaa Lyoussi

Background and Aim: Hexavalent chromium (Cr (VI)) compounds have been shown to induce nephrotoxicity associated with oxidative stress in humans and animals. The aim of the present study was to investigate the nephroprotective effect of bee propolis, as highly antioxidant natural product, in vivo using an animal model. Materials and Methods: First of all, total phenol and flavonoid contents of propolis sample were estimated in vitro. Afterward, to study the protective effect of propolis on renal damages caused by an injection of a single dose of potassium dichromate (15 mg/kg b.wt), 24 male Wister rats were divided into test and control groups. Propolis treatment was performed by oral gavage of 100 mg/kg b.wt/day, while the control groups received water instead. The 24 h urine was collected and blood samples were withdrawn before and after each treatment for further analysis. Results: Propolis revealed to be rich in polyphenols and flavonoids. Chromate provoked a nephrotoxic effect expressed by a drastic decrease in glomerular filtration assessed by creatinine clearance. However, the administration of propolis attenuated the renal damages induced by the chromate. This attenuation can be seen by the increase of creatinine clearance when comparing propolis treated group to the non-treated group. Conclusion: Propolis showed a protective potential against chromate-induced nephrotoxicity through the amelioration of chromate's toxic effects. It might be concluded that propolis could be effective as chemoprotectant in the management of potassium dichromate-induced nephrotoxicity.

2013 ◽  
Vol 91 (9) ◽  
pp. 708-714 ◽  
Author(s):  
Xue Han ◽  
Dong-Liang Zhang ◽  
Dao-Xin Yin ◽  
Qi-Dong Zhang ◽  
Wen-Hu Liu

Asymmetric dimethylarginine (ADMA) is a risk factor for endothelial dysfunction. The polypeptide apelin has biphasic effects on blood vessels in vivo and in vitro. We investigated the effect of apelin-13 on ADMA-damaged vessels. Rats were divided among ADMA-treated and control groups, which were treated with ADMA (10 mg·(kg body mass)−1·day−1) or saline, respectively, for 4 weeks. Systolic blood pressure (SBP) was measured before and after the injection of apelin-13. The ultrastructure of endothelial cells in caudal arteries was examined using transmission electron microscopy. The reactivities of isolated caudal artery rings were observed after exposure to apelin-13, and myosin light chain (MLC) phosphorylation was assessed by immunohistochemistry in rings treated with or without apelin-13. ADMA induced hypertension and endothelial dysfunction. After injection of apelin-13, SBP declined in the control group but was elevated in the ADMA-treated group. In vitro, apelin-13 caused relaxation in rings in the control group, but it contracted rings in the ADMA-treated group. Apelin-13 promoted MLC phosphorylation in vascular smooth muscle cells (VSMCs) in the ADMA group. These results indicate that apelin-13 might pass through ADMA-damaged endothelium and act on VSMCs to increase MLC phosphorylation, thus contributing to vasoconstriction and exacerbating hypertension.


2012 ◽  
Vol 42 (11) ◽  
pp. 2005-2010
Author(s):  
Antonio Cezar de Oliveira Dearo ◽  
Vitor Bruno Bianconi Rosa ◽  
Peter Reichmann ◽  
Milton Luis Ribeiro de Oliveira

Deep digital flexor (DDF) tenotomy is a technique employed for years to treat selected disorders of the musculoskeletal system in horses. Although two different surgical approaches (i.e. mid-metacarpal and pastern) have been described for performing the procedure, in vitro quantitative data regarding the modifications induced by either technique on the distal articular angles is lacking. Therefore, the purpose of the study reported here was to investigate the viability of a proposed biomechanical system of induced-traction used to compare the two DDF tenotomy techniques by measuring the distal articular angles of equine cadaver forelimbs. Ten pairs of forelimbs were collected and mounted to a biomechanical system developed to apply traction at the toe level. Dorsal articular angles of the metacarpophalangeal (MP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints were determined by geometric lines on radiographs taken before and after performing each technique. Comparisons between each tenotomy group and its own control, for each joint, and between the two tenotomy groups using as variable the difference between the tenotomy and control groups were tested. Despite the lack of statistical significance, the DDF tenotomy technique at the pastern level produced extension, to a lesser and greater extent, of the PIP and DIP joints, respectively when compared to the mid-metacarpal level. No remarkable differences could be observed for the MP joint. The developed traction-induced biomechanical construct seemed to be effective in producing valuable quantitative estimations of the distal articular angles of equine cadaver forelimbs subjected to different DDF tenotomy techniques.


Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 300 ◽  
Author(s):  
Shulan Li ◽  
Juan Liu ◽  
Mengya Zhang ◽  
Yuan Chen ◽  
Tianxing Zhu ◽  
...  

Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl4)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl4-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl4 model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl4-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl4-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c+ dendritic cells into the liver tissues of CCl4-treated mice. These results indicated that eckol has the protective effect on CCl4-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation.


1992 ◽  
Vol 263 (6) ◽  
pp. E1131-E1133
Author(s):  
A. Zeidler ◽  
P. Edwards ◽  
J. Goldman ◽  
S. Kort ◽  
W. P. Meehan ◽  
...  

The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
S. P. Daniels ◽  
J. Leng ◽  
J. R. Swann ◽  
C. J. Proudman

Abstract Background Anthelmintic treatment is a risk factor for intestinal disease in the horse, known as colic. However the mechanisms involved in the onset of disease post anthelmintic treatment are unknown. The interaction between anthelmintic drugs and the gut microbiota may be associated with this observed increase in risk of colic. Little is known about the interaction between gut microbiota and anthelmintics and how treatment may alter microbiome function. The objectives of this study were: To characterise (1) faecal microbiota, (2) feed fermentation kinetics in vitro and (3) metabolic profiles following moxidectin administration to horses with very low (0 epg) adult strongyle burdens. Hypothesis: Moxidectin will not alter (1) faecal microbiota, (2) feed fermentation in vitro, or, (3) host metabolome. Results Moxidectin increased the relative abundance of Deferribacter spp. and Spirochaetes spp. observed after 160 h in moxidectin treated horses. Reduced in vitro fibre fermentation was observed 16 h following moxidectin administration in vivo (P = 0.001), along with lower pH in the in vitro fermentations from the moxidectin treated group. Metabolic profiles from urine samples did not differ between the treatment groups. However metabolic profiles from in vitro fermentations differed between moxidectin and control groups 16 h after treatment (R2 = 0.69, Q2Y = 0.48), and within the moxidectin group between 16 h and 160 h post moxidectin treatment (R2 = 0.79, Q2Y = 0.77). Metabolic profiles from in vitro fermentations and fermentation kinetics both indicated altered carbohydrate metabolism following in vivo treatment with moxidectin. Conclusions These data suggest that in horses with low parasite burdens moxidectin had a small but measurable effect on both the community structure and the function of the gut microbiome.


Author(s):  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Bo Bo Win Maung ◽  
Robert S. Mansbach ◽  
Michael R. Hodges ◽  
...  

Candida endophthalmitis is a serious sight-threatening complication of candidemia that may occur before or during antifungal therapy. Hematogenous Candida meningoencephalitis (HCME) is also a serious manifestation of disseminated candidiasis in premature infants, immunosuppressed children, and immunocompromised adults. We evaluated the antifungal efficacy and pharmacokinetics of the prodrug fosmanogepix (APX001) in a rabbit model of endophthalmitis/HCME. Manogepix (APX001A), the active moiety of prodrug fosmanogepix, inhibits the fungal enzyme Gwt1, and is highly active in vitro and in vivo against Candida spp., Aspergillus spp., and other fungal pathogens. Plasma pharmacokinetics of manogepix after oral administration of fosmanogepix on Day-6 at 25, 50, and 100 mg/kg resulted in plasma Cmax of 3.96±0.41, 4.14±1.1, and 11.5±1.1 μg/ml, respectively, and AUC0-12 of 15.8±3.1, 30.8±5.0, 95.9±14 μg·h/ml, respectively. Manogepix penetrated into the aqueous humor, vitreous, and choroid with liquid to plasma ratios ranging from 0.19 to 0.52, 0.09 to 0.12, and 0.02 to 0.04, respectively. These concentrations correlated with a significant decrease in Candida albicans burden in vitreous (>101-103) and choroid (>101-103) (P≤0.05 and P≤0.001, respectively). Aqueous humor had no detectable C. albicans in treatment and control groups. The tissue/plasma concentration ratios of manogepix in meninges, cerebrum, cerebellum, and spinal cord were approximately 1:1, which correlated with a >102-104 decline of C. albicans in tissue vs control (P≤0.05). Serum and CSF (1→3)-β-D-glucan levels demonstrated significant declines in response to fosmanogepix treatment. These findings provide an experimental foundation for fosmanogepix in treatment of Candida endophthalmitis and HCME and de-risk the clinical trials of candidemia and invasive candidiasis.


Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 108-119 ◽  
Author(s):  
Matheus Marques Milagre ◽  
Renata Tupinambá Branquinho ◽  
Maira Fonseca Gonçalves ◽  
GMP de Assis ◽  
Maykon Tavares de Oliveira ◽  
...  

AbstractBackground:The current drugs for Chagas disease treatment present several limitationsMethods:The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.Results:The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.Conclusion:GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4891-4891
Author(s):  
Mohamed H. Zaki ◽  
Zhao Zhou ◽  
Francis L. McCabe ◽  
Hillary J. Millar ◽  
Christine McCauley ◽  
...  

Abstract IL-6 is a multifunctional cytokine that is implicated in the pathophysiology of several malignant diseases including MM, an incurable malignant plasma cell disorder. IL-6 is known to enhance proliferation, differentiation and survival of malignant plasma cells in MM through an autocrine and/or a paracrine mechanism that involves the inhibition of apoptosis of the malignant cells, induction of resistance to chemotherapy and contribution to angiogenesis. Moreover, elevated levels of IL-6 in serum of patients with MM correlate with disease activity, unfavorable prognosis and refractoriness to standard therapy. Blocking IL-6 has been postulated to be an effective therapy (Klein et al, 1995) and several studies have investigated the effect of blocking IL-6 on MM cells and cell lines both in vitro and in vivo. However, the lack of a reliable IL-6 dependent MM model has hindered these efforts. Recently, mouse plasmacytomas were described as appropriate models to study the biology of human MM (Iankov et al., Immunobiology2004; 208(5)). The current study describes a new in vivo IL-6 dependent mouse plasmacytoma model in SCID mice. Mice were inoculated subcutaneously with 1 x 106 7TD1 cells, an IL-6 dependent mouse hybridoma/plasmacytoma cell line. Three days after tumor inoculation, mice were treated 2x/week i.p. with either PBS or 25 mg/kg of anti-mouse IL-6 (R & D systems, Clone MP520F3) or control mAb. Thirteen days after tumor implantation the mean tumor volume in the control mAb group and PBS group was 3204 +/− 360 SEM mm3, n = 10; and 2430 +/− 189 SEM mm3, n = 10, respectively. The mean tumor volume in the anti-IL-6 treated group was 635 +/− 149 SEM mm3, n = 10. Serum was tested by ELISA for levels of IL-6 and IgM (a mAb that is produced by 7TD1 cell line). IL-6 serum level was undetectable in naïve non-tumor bearing SCID mice. The IL-6 levels in the PBS treated group and control mAb group were 121 +/− 32 pg/ml and 125 +/− 14 pg/ml, respectively. IL-6 levels in animals treated with rat-anti- mouse IL-6 were not detected due to interference of the mAb with the ELISA. Serum IgM levels in optical density (OD) were 0.02 +/− 0.005 in the naïve non-tumor bearing animals, 0.80 +/− 0.02 in the PBS group, 0.77 +/− 0.03, in the control mAb group, and 0.19 +/− 0.17 in the rat anti-mouse IL-6 group. In conclusion the current study showed that 7TD1cells could be grown in SCID mice. Serum levels of both IgM and IL-6 were significantly elevated in the PBS and control mAb treated tumor-bearing animals. There was a significant reduction in the IgM levels in the rat anti-mouse IL-6 treated group (P <0.0001), a positive correlation between final tumor weight and serum IgM level (P < 0.0001, r2 = 0.782) and a 74% inhibition of tumor growth relative to either control mAb or vehicle control (P <0.0001). Taken together the current study introduces a new IL-6 dependant mouse plasmacytoma model that can be used to study the biology of MM and to test the efficacy of IL-6 blocking agents in vivo.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Hossein Yousofi Darani ◽  
Narges Soozangar ◽  
Soliman Khorami ◽  
Fatomeh Taji ◽  
Mortaza Yousofi ◽  
...  

Bothin vitroandin vivomodels have demonstrated that some parasites can interfere with tumor cell growth. The present study investigates the anticancer activity of hydatid cyst protoscolices on WEHI-164 fibrosarcoma cells and baby hamster kidney (BHK) fibroblast cellsin vitro. Those above two cell types were treated with live hydatid cyst protoscolices or left untreated for control groups. After 48 h, lactate dehydrogenase (LDH) and cell counts were assayed for both treated cells and control groups. Following treatment with hydatid cyst protoscolices, cell proliferation of both cell types was inhibited, and lysis of fibrosarcoma cells increased. Based on these results, it appears that hydatid cyst protoscolices have strong anticancer activity, and additional studies are needed to further clarify the mechanisms of this activity.


Hand ◽  
2018 ◽  
Vol 15 (2) ◽  
pp. 264-270 ◽  
Author(s):  
Kunihide Muraoka ◽  
Wei Le ◽  
Anthony W. Behn ◽  
Jeffrey Yao

Background: We have reported that bioactive sutures coated with bone marrow–derived mesenchymal stem cells (BMSCs) enhance tendon repair strength in an in vivo rat model. We have additionally shown that growth differentiation factor 8 (GDF-8, also known as myostatin) simulates tenogenesis in BMSCs in vitro. The purpose of this study was to determine the possibility of BMSC-coated bioactive sutures treated with GDF-8 to increase tendon repair strength in an in vivo rabbit tendon repair model. Methods: Rabbit BMSCs were grown and seeded on to 4-0 Ethibond sutures and treated with GDF-8. New Zealand white rabbits’ bilateral Achilles tendons were transected and randomized to experimental (BMSC-coated bioactive sutures treated with GDF-8) or plain suture repaired control groups. Tendons were harvested at 4 and 7 days after the surgery and subjected to tensile mechanical testing and quantitative polymerase chain reaction. Results: There were distinguishing differences of collagen and matrix metalloproteinase RNA level between the control and experimental groups in the early repair periods (day 4 and day 7). However, there were no significant differences between the experimental and control groups in force to 1-mm or 2-mm gap formation or stiffness at 4 or 7 days following surgery. Conclusions: BMSC-coated bioactive sutures with GDF-8 do not appear to affect in vivo rabbit tendon healing within the first week following repair despite an increased presence of quantifiable RNA level of collagen. GDF-8’s treatment efficacy of the early tendon repair remains to be defined.


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