RESUMO

The discovery of a new drug requires over a billion dollars and around 12 years of research efforts, and toxicity is the leading reason for the failure to approve candidate drugs. Many alternative methods have been validated to detect toxicity as early as possible to diminish the waste of resources and efforts in medicinal chemistry research, and in vivo alternative methods are especially valuable for the amount of information they can provide at little cost and in a short time. In this work, we present a review of the literature published between the years 2000 and 2021 on in vivo alternative methods of toxicity screening employed in medicinal chemistry, which we believe will be useful because, in addition to shortening the research time, these studies provide much additional information aside from the toxicity of drug candidate compounds. These in vivo models include zebrafish, Artemia salina, Galleria mellonella, Drosophila melanogaster, planarians, and Caenorhabditis elegans. The most published ones in the last decade were zebrafish, D. melanogaster, and C. elegans due to their reliability, ease, and cost-effectiveness in implementation and flexibility. Special attention is given to C. elegans because of its rising popularity, a wide range of uses, including toxicity screening, and active effects measurement, from antioxidant effects to anthelmintic and antimicrobial activities, and its fast and reliable results. Over time, C. elegans also became a viable high-throughput (HTS) automated drug screening option. Additionally, this manuscript lists briefly the other screening methods used for the initial toxicological analyses and the role of alternative in vivo methods in these scenarios, classifying them as in silico, in vitro and alternative in vivo models that have been receiving a growing increase in interest in recent years.

Assuntos

RESUMO

Bovine in vitro embryo production (IVP) has been around for about three decades. Over the years, it has gained a reputation as one of the most applicable of the high-tech bovine assisted reproduction techniques. It is well known that its ups and downs are basically driven by economic imperatives depending on the agricultural system in which it is used. In parallel, there has always been a strong in terest in the bovine embryo as an in vitro model for basic research purposes. This mini-review focuses on a few more recent applications of bovine IVP that can be useful for both cattle breeding business and research purposes, namely the development of a single oocyte culture system and, as an example, its possible use as a toxicity screening tool.(AU)

Assuntos

RESUMO

Bovine in vitro embryo production (IVP) has been around for about three decades. Over the years, it has gained a reputation as one of the most applicable of the high-tech bovine assisted reproduction techniques. It is well known that its ups and downs are basically driven by economic imperatives depending on the agricultural system in which it is used. In parallel, there has always been a strong in terest in the bovine embryo as an in vitro model for basic research purposes. This mini-review focuses on a few more recent applications of bovine IVP that can be useful for both cattle breeding business and research purposes, namely the development of a single oocyte culture system and, as an example, its possible use as a toxicity screening tool.

Assuntos

RESUMO

Three lethality bioassays, using the salt-water crustacean Artemia salina Leach, Artemiidae, (conventional 96 microwell plate test and the Artoxkit M microbiotest) and the freshwater crustacean Thamnocephalus platyurus Packard, Thamnocephalidae, (Thamnotoxkit F microbiotest), were compared using extracts of ten Guatemalan plant species. It was previously observed that five of them have anti-Artemia activity. These were: Solanum americanum Mill., Solanaceae, Gliricidia sepium (Jacq.) Kunth ex Walp., Fabaceae, Neurolaena lobata (L.) Cass., Asteraceae, Petiveria alliacea L., Phytolaccaceae, and Ocimum campechianum Mill., Lamiaceae. The five others: Curatella americana L., Dilleniaceae, Prunus barbata Koehne, Rosaceae, Quercus crispifolia Trel., Fagaceae, Rhizophora mangle L., Rhizophoraceae, and Smilax domingensis Willd., Smilacaceae, do not. All plants without anti-Artemia activity had no lethal effects in both assays with A. salina. For the plants with anti-Artemia activity the Artoxkit M was not sensitive to G. sepium and the conventional Artemia test was not sensitive to S. americanum, G. sepium and N. lobata. All the plant extracts, except for that of C. americana, had lethal effects on T. platyurus and the lethal median concentration (LC50) levels for this organism were in all cases substantially lower than those of the salt-water test species. This study revealed that T. platyurus is a promising test species worth further in depth investigation for toxicity screening of plant extracts with potential medicinal properties.

Três bioensaios de letalidade com o crustáceo de água salgada Artemia salina Leach, Artemiidae, (teste convencional em microplaca de 96 poós Artoxkit microbiotest M) e o crustáceo de água doce Thamnocephalus platyurus Packard, Thamnocephalidae (Thamnotoxkit microbiotest F), foram comparados utilizando extratos de dez espécies de plantas da Guatemala. Foi previamente observado que cinco delas possuem atividade anti-Artemia: Solanum americanum Mill., Solanaceae, Gliricidia sepium (Jacq.) Kunth ex Walp., Fabaceae, Neurolaena lobata (L.) Cass., Asteraceae, Petiveria alliacea L., Phytolaccaceae e Ocimum campechianum Mill., Lamiaceae. As outras cinco espécies, Curatella americana L., Dilleniaceae, Prunus barbata Koehne, Rosaceae, Quercus crispifolia Trel., Fagaceae, Rhizophora mangle L., Rhizophoraceae e Smilax domingensis Willd., Smilacaceae, não. Todas as plantas sem atividade anti-Artemia não tiveram nenhum efeito letal em ambos os ensaios com A. salina. Para as plantas com atividade anti-Artemia o M Artoxkit não foi sensível a G. sepium e teste convencional de Artemia não foi sensível a S. americanum, G. sepium e N. lobata. Todos os extratos vegetais, exceto o de C. americana, apresentaram um efeito letal sobre T. platyurus e a concentração letal média (CL50) para este organismo em todos os casos foram substancialmente inferiores aos da espécie de teste de água salgada. Este estudo revelou que T. platyurus é teste promissor para uma investigação aprofundada na seleção de extratos de plantas com potenciais propriedades medicinais.