The model beetle Tribolium castaneum can be used as an early warning system for transgenerational epigenetic side effects caused by pharmaceuticals
Authors : Linda Bingsohna, Eileen Knorr, Andreas Vilcinskas
Abstract
Currently, pharmaceuticals undergo limited testing for transgenerational and epigenetic side effects. The utilization of vertebrates as preclinical research models is hindered by their lengthy generation times, limited offspring numbers, and ethical concerns. On the other hand, invertebrates such as insects offer advantages like rapid breeding, abundant progeny, and ethical acceptability, making them suitable for high-throughput screening.
In this study, we established Tribolium castaneum (red flour beetle) as a model organism to assess the impact of drugs on complex fitness parameters and the expression of epigenetic regulatory genes. Specifically, we investigated the effects of the psychoactive drug valproic acid (VPA), a histone deacetylase inhibitor, and the antioxidant curcumin, a histone acetyltransferase inhibitor, by supplementing them in the beetle's diet.
Our findings revealed that VPA led to delayed development, reduced longevity, and increased body weight in female beetles compared to those on a control diet. Moreover, fertility and fecundity declined, and the expression of epigenetic regulatory genes was induced in the untreated F1 generation. In contrast, curcumin did not affect development or body weight significantly but increased longevity. It also caused a notable reduction in fertility and induced the expression of epigenetic regulatory genes primarily in the treated F0 generation.
Remarkably, the effects observed in T. castaneum when administering VPA and curcumin align with the effects observed in vertebrate models, confirming the potential usefulness of this beetle as an alternative model for screening the epigenetic effects of drugs. Furthermore, T. castaneum serves as a valuable early warning system for identifying transgenerational epigenetic risk factors that are challenging to detect in mammals.
Overall, our study highlights the importance of using invertebrate models like T. castaneum to assess the transgenerational and epigenetic impacts of drugs, providing insights that complement traditional vertebrate testing methods.
Abbreviations
DPH, diphenhydramine; HAT, histone acetyltransferase; HDAC, histone deacetylase; KAT, lysine acetyltransferase; MBD, methyl-CpG binding domain protein; Mt, methyltransferase; Nap1, nucleosome assembly protein 1; Sap, Sin3A-associated protein; Sin3A, SIN3 transcription regulator family member A; Sir, sirtuin; SIRT, sirtuin; VPA, valproic acid
Keywords
Curcumin; Drug development; Epigenetics; Insect models; Preclinical research; Tribolium castaneum; Valproic acid
Citation: Linda Bingsohna, Eileen Knorr, Andreas Vilcinskas The model beetle Tribolium castaneum can be used as an early warning system for transgenerational epigenetic side effects caused by pharmaceuticals doi:10.1016/j.cbpc.2016.03.002
Received: 21 November 2015 Revised: 25 February 2016 Accepted: 9 March 2016 Available online: 10 March 2016
Copyright: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Competing interest
The authors declare that they have no competing interests.
Author contributions
LB performed all experiments and data analyses. EK introduced Tribolium handling. LB and AV conceived the study and drafted parts of the manuscript. All authors read and approved the manuscript.
Acknowledgments
The authors acknowledge financial support from the Hessen State Ministry of Higher Education, Research and the Arts (HMWK) via the collaborative research projects granted under the LOEWE Centers for “Insect Biotechnology and Bioresources” and “Translational Pharmaceutical Research”. The authors thank Dr. Richard M. Twyman for editing the manuscript and Prof. Dr. Michael Parnham (Fraunhofer Institute for Molecular Biology and Applied Ecology) for providing samples of VPA and curcumin.
