Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation
In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt) Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crysta...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-12-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/7/12/4881 |
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| author | Bélin Poletto Mezzomo Ana Luisa Miranda-Vilela Cesar Koppe Grisolia |
| author_facet | Bélin Poletto Mezzomo Ana Luisa Miranda-Vilela Cesar Koppe Grisolia |
| author_sort | Bélin Poletto Mezzomo |
| collection | DOAJ |
| description | In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt) Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o.) or with a single intraperitoneal (i.p.) injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed). This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling. |
| first_indexed | 2024-04-11T20:38:50Z |
| format | Article |
| id | doaj.art-56b3020183f14d83aa9f1870577ef8f1 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T20:38:50Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-56b3020183f14d83aa9f1870577ef8f12022-12-22T04:04:17ZengMDPI AGToxins2072-66512015-12-017125348535810.3390/toxins7124881toxins7124881Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further InvestigationBélin Poletto Mezzomo0Ana Luisa Miranda-Vilela1Cesar Koppe Grisolia2Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, BrazilDepartment of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, BrazilDepartment of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, BrazilIn addition to their applicability as biopesticides, Bacillus thuringiensis (Bt) Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o.) or with a single intraperitoneal (i.p.) injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed). This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling.http://www.mdpi.com/2072-6651/7/12/4881Bacillus thuringiensisδ-endotoxinsCry1Ac toxinbiosafetyhematoxicicitygenotoxicity |
| spellingShingle | Bélin Poletto Mezzomo Ana Luisa Miranda-Vilela Cesar Koppe Grisolia Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation Toxins Bacillus thuringiensis δ-endotoxins Cry1Ac toxin biosafety hematoxicicity genotoxicity |
| title | Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation |
| title_full | Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation |
| title_fullStr | Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation |
| title_full_unstemmed | Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation |
| title_short | Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation |
| title_sort | toxicological evaluation of a potential immunosensitizer for use as a mucosal adjuvant bacillus thuringiensis cry1ac spore crystals a possible inverse agonist that deserves further investigation |
| topic | Bacillus thuringiensis δ-endotoxins Cry1Ac toxin biosafety hematoxicicity genotoxicity |
| url | http://www.mdpi.com/2072-6651/7/12/4881 |
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