Conditions and Possible Mechanisms of VCD-induced Ovarian Failure

Wei Liu, Ling-Yan Wang, Xiao-Xue Xing and Guan-Wei Fan

Perimenopause is an important period in women’s lives, in which they experience a series of physiological changes. Current animal models of perimenopause fail to adequately replicate this particular stage in female life, while current in vitro models are too simplistic and cannot account for systemic effects. Neither the naturally-ageing animal model, nor the ovariectomised animal model, mimic the natural transitional process that is the menopause. In vivo and in vitro studies have confirmed that the occupational chemical, 4-vinylcyclohexene diepoxide (VCD), can cause selective destruction of the ovarian primordial and primary follicles of rats and mice by accelerating the apoptotic process, which successfully mimics the perimenopausal state in women. However, it is the in vivo VCD-induced rodent perimenopausal models that are currently the most widely used in research, rather than any of the available in vitro models. Studies on the mechanisms involved have found that VCD induces ovotoxicity via interference with the c-kit/kit ligand and apoptotic signalling pathways, among others. Overall, the VCD-induced perimenopausal animal models have provided some insight into female perimenopause, but they are far from ideal models of the human situation.

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In Vitro Models for Studying Renal Stone Formation: A Clear Alternative

Felix Grases, Rafael M. Prieto and Antonia Costa-Bauzá

This paper discusses the limitations of using laboratory animals for direct in vivo observation of the development of renal stones. In fact, the majority of hypotheses related to mechanisms of stone formation have been based on the results of in vitro experiments. The relevance of in vitro experiments that allow the study of urolithiasis depends upon the degree of correspondence between the experimental conditions and those prevailing in the stone-forming kidney in vivo. For this reason, several in vitro experimental systems that attempt to reproduce the conditions found in vivo have been developed in order to study renal stone formation, which have been classified into two main groups: a) models to study papillary stone formation; and b) models to study “sedimentary” stone formation. These models are briefly described in this paper, and the information obtained was compared with that resulting from a study of the fine structure of real human renal calculi, in order to prove the validity of the models. It was concluded that the experimental in vitro models can closely reproduce the renal conditions under which human calculi are developed. This allows important data to be obtained about the aetiology of renal lithiasis, which is of great relevance to the development of effective treatments for this disease. Therefore, experimental in vitro models constitute a clear alternative to the use of laboratory animals.
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Structural Basis of the Toxicity of Chemicals in Cultured Human HeLa Cells

Xinyu Zhu and Herbert S. Rosenkranz

A coherent structure-activity relationship (SAR) model was derived from data based on the toxicity of chemicals in cultured human HeLa cells. The ability to construct such a model indicates that toxicity is a function of a finite number of mechanisms. A comparison of the HeLa SAR model with models that describe other toxicological phenomena demonstrated significant mechanistic similarities with systemic toxicity in rodents and ocular irritation in rabbits. Overall, the present analyses support the hypothesis that the inclusion of a battery of cell toxicity assays together with toxicokinetic models will result in a more predictive model of systemic toxicity in humans.
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