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Protective effects of glucose-6-phosphate and NADP against alpha-chaconine-induced developmental toxicity in Xenopus
J R Rayburn1, J A Bantle, C W Qualls
1US Environmental Protection Agency, Environmental Research Laboratory, Gulf Breeze, FL 32561, USA.
Abstract:
In previous studies a metabolic activation system (MAS) composed of Aroclor 1254-induced rat liver microsomes led to an apparent reduction of potato glycoalkaloid developmental toxicity in the frog embryo teratogenesis assay-Xenopus (FETAX). The reasons for this reduction were investigated in this study. The effect of the exogenous MAS on glycoalkaloid developmental toxicity was examined in two experiments in which a concentration series of alpha-chaconine was tested with a MAS with and without a reduced nicotinamide adenine dinucleotide (NADPH) generator system consisting of NADPH, oxidized nicotinamide adenine dinucleotide (NADP), glucose-6-phosphate (G6P) and glucose-6-phosphate dehydrogenase. The NADPH generator system and each of its individual components were tested at a single high concentration of alpha-chaconine to evaluate their potential effects on toxicity. The findings indicated that the protective effect of the MAS was not the result of detoxification by microsomal enzyme systems, but was caused by two components of the NADPH generator system, namely NADP and G6P. G6P was more protective of alpha-chaconine-induced toxicity than NADP at the concentrations tested. Thus, FETAX with a MAS must be performed with appropriate controls that take into account the possible interactions with individual components of the system.
Insights
The metabolic activation system (MAS) does not reduce potato glycoalkaloid toxicity through enzyme detoxification. Instead, components like NADP and G6P in the NADPH generator system offer protection in frog embryo tests.
Area of Science:
- Developmental Toxicology
- Environmental Toxicology
- Pharmacology
Background:
- Previous studies indicated a reduction in potato glycoalkaloid developmental toxicity using a metabolic activation system (MAS) in the frog embryo teratogenesis assay-Xenopus (FETAX).
- The underlying mechanisms for this observed protective effect were not fully understood.
Purpose of the Study:
- To investigate the reasons behind the apparent reduction in glycoalkaloid developmental toxicity when using a MAS in the FETAX assay.
- To determine whether the protective effect is due to microsomal enzyme systems or other components of the MAS.
Main Methods:
- Examined the effect of an exogenous MAS on alpha-chaconine developmental toxicity in FETAX.
- Tested a concentration series of alpha-chaconine with and without a reduced nicotinamide adenine dinucleotide (NADPH) generator system.
- Evaluated the impact of the NADPH generator system and its individual components (NADPH, NADP, G6P, glucose-6-phosphate dehydrogenase) on toxicity.
Main Results:
- The protective effect of the MAS was not attributed to microsomal enzyme detoxification.
- Two components of the NADPH generator system, NADP and G6P, were identified as responsible for the protective effect.
- G6P demonstrated greater protection against alpha-chaconine toxicity than NADP at the tested concentrations.
Conclusions:
- The protective effect observed in FETAX with MAS is primarily due to NADP and G6P, not enzymatic detoxification.
- Appropriate controls are essential when using MAS in FETAX to account for interactions with individual system components.