scholarly journals Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid

2013 ◽  
Vol 58 (1) ◽  
pp. 481-488 ◽  
Author(s):  
Kelly C. Kato ◽  
Eliane Morais-Teixeira ◽  
Priscila G. Reis ◽  
Neila M. Silva-Barcellos ◽  
Pascal Salaün ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Side Effects ◽  
Protective Effect ◽  
Peroxidase Activity ◽  
Hepatic Uptake ◽  
Control Group ◽  
Content Type ◽  
Meglumine Antimoniate ◽  
Effective Strategies

ABSTRACTPentavalent antimonial drugs such as meglumine antimoniate (Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including cardiotoxicity and hepatotoxicity, during the treatment of leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of meglumine antimoniate, as well as the protective effect of the antioxidant ascorbic acid (AA) during antimonial chemotherapy in a murine model of visceral leishmaniasis. BALB/c mice infected withLeishmania infantumwere treated intraperitoneally at 80 mg of Sb/kg/day with commercial meglumine antimoniate (Glu) or a synthetic meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations, peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial therapy.

An ESR study of the peroxidase reaction catalyzed by human methaemoglobin and methaemoglobin-haptoglobin complex

1991 ◽  
Vol 56 (4) ◽  
pp. 923-932
Author(s):  
Jana Stejskalová ◽  
Pavel Stopka ◽  
Zdeněk Pavlíček
Keyword(s):  
Hydrogen Peroxide ◽  
Ascorbic Acid ◽  
Amino Acid ◽  
Peroxidase Activity ◽  
Amino Acid Analysis ◽  
Superoxide Radical ◽  
Esr Spectra ◽  
The Other ◽  
Delocalized Electron

The ESR spectra of peroxidase systems of methaemoglobin-ascorbic acid-hydrogen peroxide and methaemoglobin-haptoglobin complex-ascorbic acid-hydrogen peroxide have been measured in the acetate buffer of pH 4.5. For the system with methaemoglobin an asymmetrical signal with g ~ 2 has been observed which is interpreted as the perpendicular region of anisotropic spectrum of superoxide radical. On the other hand, for the system with methaemoglobin-haptoglobin complex the observed signal with g ~ 2 is symmetrical and is interpreted as a signal of delocalized electron. After realization of three repeatedly induced peroxidase processes the ESR signal of the perpendicular part of anisotropic spectrum of superoxide radical is distinctly diminished, whereas the signal of delocalized electron remains practically unchanged. An amino acid analysis of methaemoglobin along with results of the ESR measurements make it possible to derive a hypothesis about the role of haptoglobin in increasing of the peroxidase activity of methaemoglobin.

scholarly journals Direct evidence for a key role of protein kinase C in the development of vasospasm after subarachnoid hemorrhage

1992 ◽  
Vol 76 (4) ◽  
pp. 635-639 ◽  
Author(s):  
Shigeru Nishizawa ◽  
Nobukazu Nezu ◽  
Kenichi Uemura
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Direct Evidence ◽  
Control Group ◽  
Content Type ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Fine Print

✓ Vascular contraction is induced by the activation of intracellular contractile proteins mediated through signal transduction from the outside to the inside of cells. Protein kinase C plays a crucial role in this signal transduction. It is hypothesized that protein kinase C plays a causative part in the development of vasospasm after subarachnoid hemorrhage (SAH). To verify this directly, the authors measured protein kinase C activity in canine basilar arteries in an SAH model with (γ-32P)adenosine triphosphate and the data were compared to those in a control group. Protein kinase C is translocated to the membrane from the cytosol when it is activated, and the translocation is an index of the activation; thus, protein kinase C activity was measured both in the cytosol and in the membrane fractions. Protein kinase C activity in the membrane in the SAH model was remarkably enhanced compared to that in the control group. The percentage of membrane activity to the total was also significantly greater in the SAH vessels than in the control group, and the percentage of cytosol activity in the SAH group was decreased compared to that in the control arteries. The results indicate that protein kinase C in the vascular smooth muscle was translocated to the membrane from the cytosol and was activated when SAH occurred. It is concluded that this is direct evidence for a key role of protein kinase C in the development of vasospasm.

Anti-inflammatory, Antioxidant, Lung and Liver Protective Activity of Galaxaura oblongata as Antagonistic Efficacy against LPS using Hematological Parameters and Immunohistochemistry as Biomarkers

2021 ◽  
Vol 19 ◽  
Author(s):  
Asmaa Nabil-Adam ◽  
Mohamed A. Shreadah
Keyword(s):  
Protective Effect ◽  
Hematological Parameters ◽  
Control Group ◽  
In Vivo Assays ◽  
Induction Group ◽  
Anti Inflammatory ◽  
In Vitro Effects

Background: This study aimed to investigate the potential bioactivity and the ameliorative role of Galaxaura oblongata (G. oblongata) against LPS-induced toxicity by using hematological parameters. Objective: It is aimed also to examine its protective effect using the immunohistochemistry of liver and lungs as biomarkers in male BALB/C albino mice. Materials and Methods: the current study carried out using different in-vitro and in-vivo assays such as phytochemical, antioxidants, anti-inflammatory for in-vitro where the hematological and immunohistochemistry for lung and liver were investigated in vivo. Results: There are no previous studies were performed to investigate the in vivo and in vitro effects of the G. oblongata extracts as antioxidant and anti-inflammatory due to their rareness compared to other red algae. LPS treated mice revealed a significant decrease in total number of WBCs, RBCs, platelets, and HGB%, MPV, MCV and MCHC compared to the control group. On contrast, the HCT and MCHC were increased in the induction group which was treated with LPS compared to the control group. Furthermore, the immunohistochemistry results of the present study revealed the protective effect of G. oblongata compared to the induction group. G. oblongata can be used as protective marine natural products against the toxicity induced by LPS. Conclusion: It exhibited a significant ameliorative role against the alterations in the hematological parameters and immunohistochemistry of liver and lungs, and helps to reduce as well as coordinate the acute inflammations caused by TNF.

Evaluation of the toxic effect of silver nanoparticles and the possible protective effect of ascorbic acid on the parotid glands of albino rats: An in vivo study

2020 ◽  
Vol 36 (6) ◽  
pp. 446-453
Author(s):  
Salma Awad Taghyan ◽  
Hend El Messiry ◽  
Medhat Ahmed El Zainy
Keyword(s):  
Silver Nanoparticles ◽  
Ascorbic Acid ◽  
Vitamin C ◽  
Protective Effect ◽  
Toxic Effect ◽  
Toxic Effects ◽  
Control Group ◽  
Albino Rats ◽  
Parotid Glands ◽  
Ductal Cells

This study aimed to evaluate the toxic effect of silver nanoparticles (AgNPs) on the parotid glands (PGs) of albino rats histologically and ultrastructurally and assess the possible protective effect of ascorbic acid as an antioxidant. Thirty male albino rats weighing between 150 mg and 200 mg were divided into three groups: the control group (C1) contained 10 rats that received 2 mg/kg (body weight (bw)) of aqueous nitrate buffer by intraperitoneal (IP) injection daily for 28 days; the AgNPs group contained 10 rats that received 2 mg/kg (bw) IP AgNPs daily for 28 days; and the AgNPs-vitamin C group contained 10 albino rats that received 2 mg/kg (bw) AgNPs IP daily for 28 days with oral administration of 100 mg/kg (bw) vitamin C in drinking water daily for 28 days. The PG acinar and ductal cells of the AgNPs group showed signs of toxicity and degeneration characterized as pleomorphic nuclei, binucleation, cytoplasmic vacuolations, and stagnated secretion in the ductal lumen. In addition to degenerated mitochondria, dilated rough endoplasmic reticulum and lysosomes were filled with AgNPs ( p < 0.001). The AgNPs-vitamin C group showed significantly less degenerative changes histologically and ultrastructurally compared to the AgNPs group ( p = 0.002). AgNPs produced significant toxic effects on the PG of albino rats, presumably through the generation of reactive oxygen species and toxic ion release, and administration of vitamin C was shown effective in decreasing these toxic effects.

A basic peroxidase isoenzyme from the grape pedicel is induced by gibberellic acid

1999 ◽  
Vol 26 (4) ◽  
pp. 387 ◽  
Author(s):  
Francisco J. Pérez ◽  
Verónica Morales
Keyword(s):  
Ascorbic Acid ◽  
Gibberellic Acid ◽  
Peroxidase Activity ◽  
Hormone Treatment ◽  
Table Grape ◽  
Guaiacol Peroxidase ◽  
Peroxidase Isoenzymes ◽  
Peroxidase Isoenzyme ◽  
Soluble Peroxidase

Soluble peroxidase activity from pedicels of seedless table grape cv. Sultana was highly stimulated by post-bloom applications of gibberellic acid (GA3) to vines. The increase in peroxidase activity was mainly due to the induction of a basic peroxidase isoenzyme (pI > 9; BPrx-HpI). The activity of two other peroxidase isoenzymes of pI 6.5 and 3.2 was not altered by the hormone treatment. BPrx-HpI was induced by GA3 in pedicels and rachis but not in berries, although in berries peroxidase activity was also stimulated by post-bloom GA3 applications. BPrx-HpI oxidised guaiacol and ortho-phenylenediamine (o-PDA), while the others peroxidases found in the pedicel and in the berry oxidised only o-PDA. Hence, BPrx-HpI was characterised as a guaiacol-peroxidase showing no activity towards ascorbic acid (ASC). The possible role of BPrx-HpI in pedicel lignification and berry-drop caused by GA3 applications to cv. Sultana vines is discussed.

scholarly journals Intermediaries and social entrepreneurship identity: implications for business model innovation

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maribel Guerrero ◽  
Carlos A. Santamaría-Velasco ◽  
Raj Mahto
Keyword(s):  
Business Model ◽  
Social Entrepreneurship ◽  
Economic Value ◽  
Control Group ◽  
Innovation Ecosystem ◽  
Content Type ◽  
The Social ◽  
Depth Analysis ◽  
Social Innovations

PurposeThe authors propose a theoretical basis for understanding the role of ecosystem intermediaries in the configuration of social entrepreneurship identities in social purpose organisations (SPOs) and their business model innovations (BMIs).Design/methodology/approachAdopting a retrospective multiple-case study, the authors offer insights into the paths/elements that determine the building of 44 social entrepreneurship identities in the context of an emerging economy (Mexico).FindingsThe study sheds light on the role of intermediaries in the configuration of the entrepreneurial identities of Mexican SPOs and BMIs, as well as several externalities generated during the process of capturing the social and economic value, especially when social innovations are focussed on solving societal, economic and ecological social problems.Research limitations/implicationsThe first limitation is related to the analysis of intermediaries within the social entrepreneurship ecosystem, which needs more conceptual and empirical evidence. The second limitation is that the analysis focussed only on intervened SPOs, as the authors did not control for non-intervened SPOs. Thus, this allows for future in-depth analysis of intermediary efficiency in a focus group (intervened SPOs) and a control group (non-intervened SPOs).Practical implicationsThe study also provides insights for Mexican SPOs on how a social entrepreneurship identity helps to capture the value creation of social innovations within an innovation ecosystem. Indeed, it is strongly aligned with the United Nations' Social Development Goals.Originality/valueThe study enhances the discussion about how intermediaries could encourage social entrepreneurial identity, as well as how intermediary intervention could facilitate the design and implementation of BMIs in the innovation ecosystem.

scholarly journals Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Anne C. G. Almeida ◽  
Maria C. B. Puça ◽  
Erick F. G. Figueiredo ◽  
Laila R. Barbosa ◽  
Yanka E. A. R. Salazar ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Ex Vivo ◽  
Plasma Concentrations ◽  
Similar Efficacy ◽  
Early Recurrence ◽  
Control Group ◽  
Recurrence Rates ◽  
Mutant Genotype ◽  
Content Type

ABSTRACT Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism.

scholarly journals Modulating Effect of Ascorbic Acid on Transport-Induced Immunosuppression in Goats

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Ndazo Salka Minka ◽  
Joseph Olusegun Ayo
Keyword(s):  
Ascorbic Acid ◽  
High Ambient Temperature ◽  
Control Group ◽  
Sterile Water ◽  
Road Transportation ◽  
Neutrophil Lymphocyte Ratio ◽  
Hot Dry Season ◽  
Transportation Stress ◽  
Group 1

The effect of 12 h road transportation on some basic blood cells and the modulating role of ascorbic acid were investigated in 40 adult Red Sokoto goats during the hot dry season. The animals were divided into two groups, GI (experimental; ) and GII (control; ). Group 1 was administered with ascorbic acid (AA) per os at a dosage rate of 100 mg/kg body weight, while GII was given 10 mL of sterile water per goat. Forty minutes after the administration and loading, the goats were transported for 12 h. The result obtained in GII goats showed that loading, transportation, high ambient temperature (AT), and relative humidity (RH) encountered during transportation induced lymphopenia, neutrophilia, and eosinopenia, which can cause immunosuppression. In GI goats, the administration of AA prior to loading and transportation ameliorated the adverse effects of loading and transportation stress on neutrophil/lymphocyte ratio and eosinopenia of the goats.

scholarly journals Therapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantum

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Cristiano C. P. dos Santos ◽  
Guilherme S. Ramos ◽  
Renata C. De Paula ◽  
Karen F. Faria ◽  
Paulo O. L. Moreira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Leishmania Infantum ◽  
Parasite Burden ◽  
Mononuclear Phagocyte ◽  
Clinical Staging ◽  
Control Group ◽  
Content Type ◽  
Meglumine Antimoniate ◽  
Pegylated Liposomes ◽  
Pretreatment Period

ABSTRACT The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.

scholarly journals Depletion of Complement Enhances the Clearance of Brucella abortus in Mice

2018 ◽  
Vol 86 (10) ◽  
Author(s):  
Gabriela González-Espinoza ◽  
Elías Barquero-Calvo ◽  
Esteban Lizano-González ◽  
Alejandro Alfaro-Alarcón ◽  
Berny Arias-Gómez ◽  
...  
Keyword(s):  
Immune System ◽  
Brucella Abortus ◽  
Innate Immune ◽  
Control Group ◽  
Bacterial Disease ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Brucellosis is a bacterial disease of animals and humans. Brucella abortus barely activates the innate immune system at the onset of infection, and this bacterium is resistant to the microbicidal action of complement. Since complement stands as the first line of defense during bacterial invasions, we explored the role of complement in B. abortus infections. Brucella abortus-infected mice depleted of complement with cobra venom factor (CVF) showed the same survival rate as mice in the control group. The complement-depleted mice readily eliminated B. abortus from the spleen and did so more efficiently than the infected controls after 7 days of infection. The levels of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-6 (IL-6) remained within background levels in complement-depleted B. abortus-infected mice. In contrast, the levels of the immune activator cytokine gamma interferon and the regulatory cytokine IL-10 were significantly increased. No significant histopathological changes in the liver and spleen were observed between the complement-depleted B. abortus-infected mice and the corresponding controls. The action exerted by Brucella on the immune system in the absence of complement may correspond to a broader phenomenon that involves several components of innate immunity.

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