Submit manuscript...
MOJ
eISSN: 2374-6912

Cell Science & Report

Letter to Editor Volume 1 Issue 2

Selecting species for pharmaceutical and medical research

Abdelaziz Ghanemi,1 Shihao Wu2

1Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, China
2University of Chinese Academy of Sciences, China

Correspondence: Abdelaziz Ghanemi, Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China, Tel 00861588709073

Received: November 17, 2014 | Published: December 7, 2014

Citation: Ghanemi A, Wu S. Selecting species for pharmaceutical and medical research. MOJ Cell Sci Rep. 2014;1(2):73-75. DOI: 10.15406/mojcsr.2014.01.00016

Download PDF

Letter to editor

Obtaining an approval either for a drug for a therapeutic use1–4 or for biomedical equipment requires in the majority of cases laboratory experiments on cells and animals to describe the divers related details including the potential toxic effects, the side effects and the optimized conditions of use or administrations. Within this letter we aim to further illustrate how to select the species of animal to conduct the required tests on or to extract the cells, organs or molecules from those species that we need for in vitro tests and based on what a species is either included or excluded. Indeed, in some case such choice can be a struggle facing the development of the files since it depends on divers factors including the type of the conducted research, the investigated organ or system and the duration of the experiment. Therefore, clarifying the related concepts remains a priority for pharmaceutical and medical research.

The choice of animal species is also conditioned by the type of researches and on the organs we are willing to investigate. Indeed, some species are suitable for certain types or experiments5 whereas others are not. Here in some illustrative examples are given. In neuroscience using monkeys, and due to the great similarity between them and humans, has allowed us to better understand the brain properties and the cognitive functions based on observations done on monkey’s brains.6,7 For the neural properties of the visual functions, cats represent a good choice since they have specific vision characteristics.8–11 Furthermore, cats are also suitable for electrophysiological studies. Tree shrew, a species believed to be biologically between insectivore and primates with specific evolutionary properties,12 is also used in neurobiological researches.13–15 In addition to its low cost, its brain has a similar structure to the human brain. Mice16,17 are commonly used due to their brains properties in term of neurobiological functions and the well tolerance they have towards the equipments used in recording. In genetics, due to their relatively simple genome and the short duration of life cycle, bacteria are used18,19 to study the mutations and the gene interactions but the bacterial usage in genetics is limited. For instance, mammalians provide a better multi-cellular and multi-organs environment to study interactions between genes and cell signals. Moreover, results obtained with mammalians would be closer to the human profile than those obtained with bacterial studies. In pharmacology, for example when evaluating steroids, and since the steroids have specific blood transporters that transport also the endogenous steroid hormones, the animal selected for such study should have similar hormones to mimic the pharmacokinetic conditions.

For more precise or local studies we may use isolated parts of organs or even insects. Drosophila is an insect with a nervous system that include many of the human neurotransmitters which made this fly a suitable insect for neurobiological and neuropharmacological studies.20–23 In addition, an animal’s heart or kidney put within a physiological solution that mimics the physiological situation (temperature, ions concentrations, nutriment etc) may be an appropriate way to both study the physiology of the organ and eventually test some drugs, although these results may mainly give data about the pharmacodynamic aspects rather than pharmacokinetics. Importantly, the influence that chemicals used as reagents or media may influence the live cells and thus, the laboratory results24,25 therefore the need for a negative control and condition optimization. In vitro cells culture is largely used in biological and pharmacological studies.26 Herein the species form which we take cells is important and also depends on the test we are willing to conduct. It is known that for neurotoxicity cells we may use cell cultures derived from neuroblastoma of mammalians and for hepato-toxicity we can use culture liver cells. It is worth mentioning that the best options remain human cells since the results are more reliable in term of medical extrapolations.

The duration of experiments represent an important factor. For instance, a species with a short duration of life would not be suitable for drugs long-term effects evaluation or chronic toxicity tests but would be convenient for acute toxicity test. Furthermore, since the different life period of an animal will correspond to different factors and conditions such as cell membranes receptors expressions, intracellular biochemical activities and the neuro-signaling27–34 which will have a strong impact on the pharmacological profile a study conducted on the animal, the short life duration will allow us to study the compounds (pharmakon or toxic agent32) effects depending on the animal age and life phases within a limited period of time. Within this context, embryonic development of Zebrafish is rapid, and its embryos are relatively large, robust, and transparent, and able to develop outside their mothers thus it is suitable for studies on embryos35–39 such as the evaluation of drugs effects. In addition, Zebrafish has at the adult age a transparent body through which it is possible to visualize in vivo biological activities such as fluid metastasis and brain activities.

Other elements could be important such as the animal weight and depending on the concentration and the nature (drugs, toxic element40 or natural products40–45) of the products we would inject into its body and the biocompatibility between the animal organs or the equipments we might implant within it body. Herein, more availability of data related to animals along with strong collaborations between experts including zoologists, biologists and doctors represent one of the key elements required to further describe the ideal species for each experimental context. The species would be the one that has the maximum common properties with the humans within a defined context for the topics we are willing to investigate by taking into consideration the influencing factors and optimize the laboratory methods towards better results.

Furthermore, genetic similarities exist between Zebrafish and humans, which made them a model to study diseases such as leukemia and some other cancers. Importantly, genetically modifies animals, such as Cre-mutant mouse strains46–48 represent an essential tool in biological and medical research. Indeed, family Alzheimer disease (FAD) genes are introduced to monkeys and mice brains through transgenic virus as one of the methods, among others,49–53 used to obtain animals models of Alzheimer disease (AD)29 used to study AD properties, pathogenesis, mechanisms and test therapeutic candidates. We conclude by emphasizing the importance of the species choice as the first step of optimizing the results of the related studies even before starting them and as the best way to ensure we can extrapolate our results and build further studies based on them.

Acknowledgements

Abdelaziz Ghanemi is a recipient of a 2013 CAS-TWAS President's Postgraduate Fellowship.

Conflict of interest

The author declares no conflict of interest.

References

  1. Rawson NS. Timeliness of review and approval of new drugs in Canada from 1999 through 2001: is progress being made? Clin Ther. 2003;25(4):1230–1247.
  2. Hartmann M, Mayer–Nicolai C, Pfaff O. Approval probabilities and regulatory review patterns for anticancer drugs in the European Union. Crit Rev Oncol Hematol. 2013;87(2):112–121.
  3. Shimazawa R, Ikeda M. Japanese regulatory system for approval of off–label drug use: evaluation of safety and effectiveness in literature–based applications. Clin Ther. 2012;34(10):2104–2116.
  4. Kataria BC, Mehta DS, Chhaiya SB. Drug lag for cardiovascular drug approvals in India compared with the US and EU approvals. Indian Heart J. 2013;65(1):24–33.
  5. Ghanemi A. Alzheimer’s disease therapies: Selected advances and future perspectives. Alexandria Journal of Medicine. 2015;51(1):1–3.
  6. Michopoulos V, Embree M, Reding K, et al. CRH receptor antagonism reverses the effect of social subordination upon central GABAA receptor binding in estradiol–treated ovariectomized female rhesus monkeys. Neuroscience. 2013;250:300–308.
  7. Rollema H, Alexander GM, Grothusen JR, et al. Comparison of the effects of intracerebrally administered MPP+ (1–methyl–4–phenylpyridinium) in three species: microdialysis of dopamine and metabolites in mouse, rat and monkey striatum. Neurosci Lett. 1989;106(3):275–281.
  8. Clark DL, Clark RA. The effects of time, luminance, and high contrast targets: revisiting grating acuity in the domestic cat. Exp Eye Res. 2013;116:75–83.
  9. Burnat K, Vandenbussche E, Zernicki B. Global motion detection is impaired in cats deprived early of pattern vision. Behav Brain Res. 2002;134(1–2):59–65.
  10. Pasternak T, Merigan WH, Flood DG, et al. The role of area centralis in the spatial vision of the cat. Vision Res. 1983;23(12):1409–1416.
  11. Chen Y, Li H, Jin Z, et al. Feedback of the amygdala globally modulates visual response of primary visual cortex in the cat. Neuroimage. 2014;84:775–785.
  12. Lin J, Chen G, Gu L, et al. Phylogenetic affinity of tree shrews to Glires is attributed to fast evolution rate. Mol Phylogenet Evol. 2014;71:193–200.
  13. Wang S, Shan D, Dai J, et al. Anatomical MRI templates of tree shrew brain for volumetric analysis and voxel–based morphometry. J Neurosci Methods. 2013;220(1):9–17.
  14. Khani A, Rainer G. Recognition memory in tree shrew (Tupaia belangeri) after repeated familiarization sessions. Behav Processes. 2012;90(3):364–371.
  15. Fouillen L, Petruzziello F, Veit J, et al. Neuropeptide alterations in the tree shrew hypothalamus during volatile anesthesia. J Proteomics. 2013;80:311–320.
  16. Nivison–Smith L, Chua J, Tan SS, et al. Amino acid signatures in the developing mouse retina. Int J Dev Neurosci. 2014;33:62–80.
  17. Hartig W, Goldhammer S, Bauer U, et al. Concomitant detection of beta–amyloid peptides with N–terminal truncation and different C–terminal endings in cortical plaques from cases with Alzheimer's disease, senile monkeys and triple transgenic mice. J Chem Neuroanat. 2010;40(1):82–92.
  18. Delcour J, Ferain T, Hols P. Advances in the genetics of thermophilic lactic acid bacteria. Curr Opin Biotechnol. 2000;11(5):497–504.
  19. Maiden MC. Population genetics of a transformable bacterium: the influence of horizontal genetic exchange on the biology of Neisseria meningitidis. FEMS Microbiol Lett. 1993;112(3):243–250.
  20. Nichols CD. Drosophila melanogaster neurobiology, neuropharmacology, and how the fly can inform central nervous system drug discovery. Pharmacol Ther. 2006;112(3):677–700.
  21. Griffith LC. Identifying behavioral circuits in Drosophila melanogaster: moving targets in a flying insect. Curr Opin Neurobiol. 2012;22(4):609–614.
  22. Ui–Tei K, Sakuma M, Watanabe Y, et al. Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system, II: Neuropeptides and amino acids. Neurosci Lett. 1995;195(3):187–190.
  23. Ui–Tei K, Nishihara S, Sakuma M, et al. Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system. I. ACh and L–dopa. Neurosci Lett. 1994;174(1):85–88.
  24. Ghanemi A. Toward overcoming the challenges facing biomedical analyses. Alexandria Journal of Medicine. 2015;51(3):277–278.
  25. Ghanemi A. Biological properties and perspective applications of “Bio–neuter” chemicals? Saudi Pharm J. 2014;22(1):1–2.
  26. Ghanemi A. Cell cultures in drug development: Applications, challenges and limitations. Saudi Pharmaceutical Journal. 2015;23(4):453–454.
  27. Ghanemi A. Targeting G protein coupled receptors–related pathways as emerging molecular therapies. Saudi Pharmaceutical Journal. 2015;23(2):115–129.
  28.  Ghanemi A, Ling H, Ming Y. New factors influencing G protein coupled receptors' system functions. Alexandria Journal of Medicine. 2013;49(1):1–5.
  29. Ghanemi A. Animal models of Alzheimer's disease: Limits and challenges. NPG Neurologie–Psychiatrie–Geriatrie. 2014;14(84):303–305.
  30. Ghanemi A. Schizophrenia and Parkinson’s disease: Selected therapeutic advances beyond the dopaminergic etiologies. Alexandria Journal of Medicine. 2013;49(4):287–291.
  31. Ghanemi A, Xintian H. Elements toward novel therapeutic targeting of the adrenergic system. Neuropeptides. 2015;49:25–35.
  32. Ghanemi A. How to define a pharmacological or a toxic food? Alexandria Journal of Medicine. 2015;51(4):359–360.
  33. Ghanemi A, Xintian H. Targeting the orexinergic system: Mainly but not only for sleep–wakefulness therapies. Alexandria Journal of Medicine. 2015;51(4):279–286.
  34. Ghanemi A. Psychiatric neural networks and neuropharmacology: Selected advances and novel implications. Saudi Pharm J. 2014;22(2):95–100.
  35. Yang B, Peng G, Gao J. Expression of unc5 family genes in zebrafish brain during embryonic development. Gene Expr Patterns. 2013;13(8):311–318.
  36. Kaur S, Abu–Asab MS, Singla S, et al. Expression pattern for unc5b, an axon guidance gene in embryonic zebrafish development. Gene Expr. 2007;13(6):321–327.
  37. Thomas–Jinu S, Houart C. Dynamic expression of neurexophilin1 during zebrafish embryonic development. Gene Expr Patterns. 2013;13(8):395–401.
  38. Peng K, Li Y, Long L, et al. Knockdown of FoxO3 a induces increased neuronal apoptosis during embryonic development in zebrafish. Neurosci Lett. 2010;484(2):98–103.
  39. Mahabir S, Chatterjee D, Gerlai R. Strain dependent neurochemical changes induced by embryonic alcohol exposure in zebrafish. Neurotoxicol Teratol. 2014;41:1–7.
  40. Ghanemi A. Is mapping borders between pharmacology and toxicology a necessity? Saudi Pharmaceutical Journal. 2014;22(6):489–490.
  41. Boubertakh B, Liu XG, Cheng XL, et al. A Spotlight on Chemical Constituents and Pharmacological Activities of Nigella glandulifera Freyn et Sint Seeds. Journal of Chemistry. 2013;2013:12.
  42. Zhang A, Sun H, Wang X. Recent advances in natural products from plants for treatment of liver diseases. Eur J Med Chem. 2013;63:570–577.
  43. Ghosh N, Ghosh R, Mandal V, et al. Recent advances in herbal medicine for treatment of liver diseases. Pharm Biol. 2011;49(9):970–88.
  44. Ghanemi A, Boubertakh B. Shorter and sturdier bridges between traditional Chinese medicines and modern pharmacology. Saudi Pharmaceutical Journal. 2015;23(3):330–332.
  45. Ghanemi A. How important is pharmacognosy for doctors and dentists? The Saudi Dental Journal. 2015;27(1):1–2.
  46. Zha L, Hou N, Wang J, et al. Collagen1alpha1 promoter drives the expression of Cre recombinase in osteoblasts of transgenic mice. J Genet Genomics. 2008;35(9):525–530.
  47. Zaremba KM, Reeder AL, Kowalkowski A, et al. Utility and limits of Hprt–Cre technology in generating mutant mouse embryos. J Surg Res. 2014;187(2):386–393.
  48. Zhao Z, Hou N, Sun Y, et al. Atp4b promoter directs the expression of Cre recombinase in gastric parietal cells of transgenic mice. J Genet Genomics. 2010;37(9):647–652.
  49. Puzzo D, Lee L, Palmeri A, et al. Behavioral assays with mouse models of Alzheimer's disease: Practical considerations and guidelines. Biochem Pharmacol. 2014;88(4):450–467.
  50. Cheng XR, Zhou WX, Zhang YX. The behavioral, pathological and therapeutic features of the senescence–accelerated mouse prone 8 strain as an Alzheimer's disease animal model. Ageing Res Rev. 2014;13:13–37.
  51. Reddy PH, McWeeney S. Mapping cellular transcriptosomes in autopsied Alzheimer's disease subjects and relevant animal models. Neurobiol Aging. 2006;27(8):1060–1077.
  52. Aso E, Lomoio S, Lopez–Gonzalez I, et al. Amyloid generation and dysfunctional immunoproteasome activation with disease progression in animal model of familial Alzheimer's disease. Brain Pathol. 2012;22(5):636–653.
  53. Loring JF, Paszty C, Rose A, et al. Rational design of an animal model for Alzheimer's disease: introduction of multiple human genomic transgenes to reproduce AD pathology in a rodent. Neurobiol Aging. 1996;17(2):173–182.
Creative Commons Attribution License

©2014 Ghanemi, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.