A prokaryote system optimization for rMEPLox expression: A promising non-toxic antigen for Loxosceles antivenom production

Saavedra-Langer, Rafael; Costa, Tamara G.F.; Lima, Sabrina A.; Costal-Oliveira, Fernanda; Martins, Christina A.; Machado-de-Ávila, Ricardo Andrez; Minozzo, João Carlos; Soccol, V. T.; Guerra-Duarte, Clara; Kalapothakis, Evanguedes; Chávez-Olortégui, Carlos

doi:10.1016/j.ijbiomac.2021.07.042

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…Some recombinant toxins, especially sphingomyelinases isoforms, were synthesized and induced the production of neutralizing antibodies, but these recombinant toxins were not entirely non-toxic to the immunized animals [2]. Thus, some chimeric proteins containing multiepitopes for Loxosceles toxins were developed to immunize animals without causing major health damage while efficiently producing neutralizing antibodies [62,63]. However, the use of animals may, in the future, be replaced using in vitro laboratory methods to produce large amounts of neutralizing antibodies.…”

Section: Limitations and Perspectivesmentioning

confidence: 99%

The Health Status of Horses Used for at Least Six Complete Cycles of Loxoscelic Antivenom Production

Miranda,

Antunes,

Minozzo

et al. 2023

Toxins

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Antivenom production against Loxosceles venom relies on horses being immunized and bled for plasma harvest. One horse can partake in several cycles of antivenom production, which will require years of constant venom and adjuvant inoculation and bleeding. The actual impact on the health of horses that participate in several antivenom-producing cycles is unknown. Therefore, this study aimed to evaluate the general health status of horses that underwent at least six cycles of loxoscelic antivenom production. Seven crossbred horses that had partaken in six to eight complete antivenom-producing cycles were used and established as the immunized group (IG). Under the same handling and general management, eleven horses were established as the control group (CG). The horses were evaluated regarding their general clinical status and had their blood sampled, and an ECG recorded. The IG presented lower RBC and PCV, despite keeping values within inferior limits for the species. Renal function was not impaired, and liver-related enzymes were higher than those in the CG, probably due to liver exertion from immunoglobulin synthesis. ECG showed some abnormalities in the IG, such as atrioventricular block and a wandering atrial pacemaker, corroborated by an increase in CK-MB. The cardiovascular abnormalities were mainly found in the horses that participated in several antivenom-producing cycles. The overall results indicate that these horses had some impairment of their general health status. Once available, some alternative, less toxic antigens should replace the venom for immunization of horses used for antivenom production.

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Section: Limitations and Perspectivesmentioning

confidence: 99%

The Health Status of Horses Used for at Least Six Complete Cycles of Loxoscelic Antivenom Production

Miranda,

Antunes,

Minozzo

et al. 2023

Toxins

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“…Loxoscelic envenoming treatment is based on observed clinical signs and includes the use of dapsone, acetylsalicylic acid, broad spectrum antibiotics, corticosteroids, specific antivenom, composed of heterologous antibodies developed in horses and new antibody treatments (5,9,10,11,12,13) . Despite these treatment options, tissue recovery after extensive dermonecrotic damage is slow and scar formation is difficult.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of mesenchymal cells and dapsone for the treatment of dermonecrotic wounds caused by Loxosceles laeta venom in rabbits

et al. 2022

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This study aimed to evaluate the efficacy of mesenchymal stem cells (MSC), alone or associated with dapsone (DAP), in treating dermonecrotic wounds caused by Loxosceles laeta venom. Twenty-five male rabbits were distributed into five groups. Negative control received ultrapure water (C-), whilst all other groups were injected with 20 μg of L. laeta venom. After 4 hours, each group received one of the following treatments: PBS (C+), DAP, MSC, and DAP+MSC. Animals were evaluated daily and photographic records made for analysis of wound area. Twelve days after, animals were euthanized and skin samples removed for histological analysis. We observed that DAP showed the best percentage of wound contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS, probably, by the increase in initial infammation after the application of stem cells, due to the fact that MSCs secrete a broad spectrum of bioactive molecules such as cytokines and growth factors that favor regeneration. Histologically, it was observed that animals of C+ showed extensive areas of necrosis, ulcers, neutrophilic infiltrate, and mineralization. Collagen deposition showed increase in MSC+DAP treatment, however vascularization remained unchanged. This is the first report using MSC and MSC+DAP as a treatment for cutaneous loxoscelism and more studies are needed to determine its use as an alternative therapy for dermonecrotic lesions caused by Loxosceles spider.

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“…O tratamento do envenenamento loxoscélico é baseado nos sinais clínicos observados e inclui o uso de dapsona, ácido acetilsalicílico, antibióticos de amplo espectro, corticosteroides, soro antiofídico específico, composto por anticorpos heterólogos desenvolvidos em equinos e novos tratamentos com anticorpos (5,9,10,11,12,13) . Apesar dessas opções de tratamento, a recuperação do tecido após extensa lesão dermonecrótica é lenta e a formação de cicatriz é difícil.…”

Section: Introductionunclassified

Avaliação de células mesenquimais e dapsona para o tratamento de feridas dermonecróticas causadas pelo veneno de Loxosceles laeta em coelhos

et al. 2022

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Resumo Este estudo teve como objetivo avaliar a eficácia das células-tronco mesenquimais (CTMs), isoladas ou associadas à dapsona (DAP), no tratamento de feridas dermonecróticas causadas pelo veneno de Loxosceles laeta. Vinte e cinco coelhos machos foram distribuídos em cinco grupos. O controle negativo recebeu água ultrapura (C-), enquanto todos os outros grupos foram injetados com 20 μg de veneno de L. laeta. Após 4 horas, cada grupo recebeu um dos seguintes tratamentos: PBS (C+), DAP, CTMs e DAP + CTMs. Os animais foram avaliados diariamente durante 12 dias, e feitos registros fotográficos para análise da ferida e no 12º dia, foram eutanasiados e, retiradas amostras de pele para análise histológica. Observou-se que a DAP apresentou o melhor percentual de contração da ferida no terceiro dia. Nos tratamentos com CTMs, observou-se uma contração negativa da ferida tanto para as CTMs isoladas, bem como a associação CTMs + DAP em relação ao PBS, possivelmente, pelo aumento da infamação inicial após a aplicação de células-tronco. Isso é devido ao fato de que as CTMs secretam um amplo espectro de moléculas bioativas como citocinas e fatores de crescimento que favorecem a regeneração. Histologicamente, observou-se que os animais de C+ apresentaram extensas áreas de necrose, úlceras, infiltrado neutrofílico, além de mineralização. Houve aumento de deposição de colágeno no tratamento CTMs + DAP, no entanto, a vascularização permaneceu inalterada. Este é o primeiro relato usando CTMs e CTMs + DAP como tratamento para loxoscelismo cutâneo e mais estudos são necessários para determinar seu uso como terapia alternativa para lesões demonecróticas causadas pela aranha Loxosceles.

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A prokaryote system optimization for rMEPLox expression: A promising non-toxic antigen for Loxosceles antivenom production

Cited by 4 publications

References 34 publications

The Health Status of Horses Used for at Least Six Complete Cycles of Loxoscelic Antivenom Production

The Health Status of Horses Used for at Least Six Complete Cycles of Loxoscelic Antivenom Production

Evaluation of mesenchymal cells and dapsone for the treatment of dermonecrotic wounds caused by Loxosceles laeta venom in rabbits

Avaliação de células mesenquimais e dapsona para o tratamento de feridas dermonecróticas causadas pelo veneno de Loxosceles laeta em coelhos

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