Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats

BACKGROUND: Oxidative stress is involved in cisplatin-nephrotoxicity. However, it has not completely established if reactive nitrogen species and nitrosative stress are involved in this experimental model. The purpose of this work was to study the role of peroxynitrite, a reactive nitrogen specie, in cisplatin-nephrotoxicity using the compound 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III) (FeTPPS), a soluble complex able to metabolize peroxynitrite. RESULTS: In rats treated with cisplatin (a single intraperitoneal dose of 7.5 mg/kg body weight), renal nitrosative stress was made evident by the increase in 3-nitrotyrosine on day 3. In addition, cisplatin-induced nephrotoxicity was evident by the histological damage of proximal tubular cells and by the increase in (a) serum creatinine, (b) blood urea nitrogen, and (c) urinary excretion of N-acetyl-β-D-glucosaminidase and total protein. Cisplatin-induced nitrosative stress and nephrotoxicity were attenuated by FeTPPS-treatment (15 mg/kg body weight, intraperitoneally, every 12 hours for 3 days). CONCLUSIONS: Nitrosative stress is involved in cisplatin-induced nephrotoxicity in rats. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration

Good Protection but Excessive Pulmonary Inflammation in Balb/C Mice Vaccinated with Mycobacterium Bovis Mce-2A Mutant after Challenge with Homologous Strains

Tuberculosis (TB) remains a major threat to public and veterinary health. Zoonotic TB (caused by Mycobacterium bovis) is present in wild animals and cattle in most developing countries, and M. bovis is also able to infect humans on a worldwide basis. Thus, the high incidence of bovine TB is a major economic problem and an additional risk to human health, being the development of new vaccines to prevent both human and bovine TB urgent and a major challenge. The aims of the present study were to characterize the pathogenicity and immunogenicity of M. bovis mce2A mutant in BALB/c mice, and then evaluate its potential as vaccine. Mutant M. bovis mce2A produced limited tissue damage (pneumonia) and lower bacilli burdens than its parental strain when administered in high dose by intratracheal inoculation, and showed limited dissemination when used as subcutaneous vaccine. Challenge experiments using low, middle and highly virulent M. tuberculosis or M. bovis strains showed similar protection conferred by mce-2 mutant than BCG. Interestingly, vaccinated animals showed low bacilli loads but high inflammatory response when were challenged with M. bovis strains, while vaccinated mice challenged with M. tuberculosis exhibited low bacilli burdens and scarce inflammation. Thus, in spite of the high genome homology between M. tuberculosis and M. bovis, it seems that there is higher antigenic recognition and in consequence extensive inflammatory response when the strain used as vaccine is homologous to the challenge strain, in this case M. bovis.Fil: Alfonseca Silva, Edgar. Universidad Nacional Autónoma de México; MéxicoFil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bigi, Fabiana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; Méxic

Therapeutic Strategies of Secretome of Mesenchymal Stem Cell

Great progress has been made in the therapeutic strategies of multiple diseases that lack curative treatments with the transplantation of mesenchymal stem cells (MSC), such as in onco-hematological diseases, myocardial infarction (MI), cerebrovascular diseases, degenerative diseases of the nervous system (multiple sclerosis, Alzheimer’s disease), and diseases of the immune system, among others. Stem cells (SC) participate in the biological processes of tissue regeneration and repair through cell replication. Recently, the beneficial therapeutic effects of SCs that are generated by the release of proteins with paracrine actions and not by cell differentiation are more well known, and 80% of the therapeutic effect of SC is attributed to paracrine actions. The MSCs release large amounts of proteins and growth factors (GF), nucleic acids, proteasomes, exosomes, and microRNA, and membrane vesicles known as the secretome are released into the extracellular space, regulating multiple biological processes. Currently, the therapeutic strategies in tissue engineering (TE) and regenerative medicine (RM) are focused on the management of products derived from cells that act, both locally and remotely, in the affected tissue or organ, achieving regenerative actions. The application of new knowledge of the secretome initiates a change in the paradigm of regenerative therapy by knowing more about and using cell products derived from cells as a “factory” for biological drugs

Toxicidad aguda y subaguda (28 días) en ratones, de la mezcla de ácido ursólico y ácido oleanólico obtenida de Bouvardia ternifolia

Los ácidos ursólico (UA) y oleanólico (OA) son triterpenos que se encuentran distribuidos en un gran número de plantas medicinales, una de ellas es la especie Bouvardia ternifolia. Estos compuestos han mostrado alrededor de 120 actividades biológicas, destacando los efectos hepatoprotector, antiinflamatorio y antimicobacteriano. A pesar de ser compuestos con un alto potencial terapéutico, no se han documentado muchos datos acerca de su toxicidad. En este artículo se describen los resultados de la evaluación de toxicidad aguda y subaguda (28 días) en ratones Balb/c de ambos sexos, tratados con la mezcla de AU/AO obtenida de B. ternifolia a dosis de 6.5 y 13 mg/kg. La DL50 fue > 300 mg/kg. Durante la administración subaguda, no hubo muerte de animales, tampoco se observaron alteraciones en su crecimiento ni alteraciones en el peso de los diferentes órganos. Los estudios de biometría hemática y química sanguínea mostraron niveles normales en todos los parámetros evaluados. Los análisis histopatológicos de los principales órganos no presentaron cambios o anormalidades. La mezcla UA/OA es practicamente inocua cuando se administra subcutaneamente en dosis única de 300 mg/kg y 13 mg/kg en dosis repetida (28 días)

The Immunoregulatory Actions of DHEA in Tuberculosis, A Tool for Therapeutic Intervention?

Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEA-S). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.Fil: Bongiovanni, Bettina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Díaz, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Santucci, Natalia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Bay, Maria Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin