Abstract
The modeling of adaptation potential decrease in rats due to modification of the diet's vitamin–mineral composition allows to increase animals' sensitivity to toxic load in reprotoxicological experiments. The threshold values of vitamins B1, B2, B3, and B6 and mineral substances Fe3+ and Mg2+ in the diet, which lead to a considerable reduction of laboratory animals' adaptation potential, have been determined as 19% (from the basic level in the diet) for males and 18% for females. The efficiency of this model has been confirmed in a reprotoxicological experiment with glyphosate as a toxic factor: the action of the toxic factor against the background of reduced availability of B vitamins and salts Fe3+ and Mg2+ led to significant changes in such indicators of reproductive function as mating efficiency, postimplantation loss, and the total number of alive pups, while the toxic effect of glyphosate was not so pronounced against the normal level of essential substances. The obtained results prove that this adaptation potential reduction model can be recommended for the research of the low-toxicity objects reproductive toxicity in rats and for the safety assessment of novel food, in particular.
Highlights
In the safety assessment of a novel food and genetically engineered organisms of plant origin, in particular, the central place is occupied by reprotoxicological studies to prove the absence of remote negative effects that may manifest themselves only in the generation. e complex research of reproductive function, pre- and postnatal progeny development usually involves the study of a large number of parameters, with a wide range of physiological fluctuations in each, whereas the heterogeneous distribution of some indicators’ values complicates the interpretation of the results, especially under conditions of toxic impact of low intensity [1,2,3]
Glyphosate (N-(phosphonomethyl)glycine) is a nonselective herbicide; its mechanism of action is based on blocking the synthesis of some essential aromatic amino acids through affecting the metabolism of shikimic acid. e key stage of this process is the synthesis of 5-enolpyruvylshikimate-3-phosphate from phosphoenolpyruvate and shikimate-3-phosphate catalyzed by 5-enolpyruvylshikimate-3-phosphate synthase. is particular enzyme is the target of glyphosate action. e described type of shikimic acid metabolism is typical of plants, algae, bacteria, fungi, and protozoans; other living forms including insects, fish, birds, mammals, and humans do not have such a metabolic pathway [6, 7]
Glyphosate herbicide was chosen as a toxic factor, whose effect on reproductive function is described in detail [14,15,16]
Summary
In the safety assessment of a novel food and genetically engineered organisms of plant origin, in particular, the central place is occupied by reprotoxicological studies to prove the absence of remote negative effects that may manifest themselves only in the generation. e complex research of reproductive function, pre- and postnatal progeny development usually involves the study of a large number of parameters, with a wide range of physiological fluctuations in each, whereas the heterogeneous distribution of some indicators’ values complicates the interpretation of the results, especially under conditions of toxic impact of low intensity [1,2,3]. The recognition of an organism’s response in the range of physiological adaptation/pseudoadaptation (compensated latent pathological process) [4] is a very difficult task even for a modern laboratory For this reason, the simulation of additional load, which reduces the adaptation potential and, eliminates the possibility of compensation for the pathological process, is a promising tool to improve the diagnostic validity of the experiment results. E result of these studies was the creation and efficiency confirmation of the in vivo model, which increases the susceptibility of the rats to the toxic factors action by reducing the supply of B vitamins Is work was aimed at proving the efficiency of adaptation potential reduction model of rats (against the background of the known toxic factor) for application in reprotoxicological experiments. Us, we have solid grounds to believe that the toxicant chosen will make an impact on laboratory animals
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