Abstract
Thymoquinone (TQ) exhibits a wide spectrum of biological activities. Most studies on the neurotoxic action of TQ have been carried out in cancer cell lines. Here, we studied the toxic effect of TQ in primary neuronal cultures in vitro. Incubation with 0.04-0.05 mM TQ for 24 h induced the death of cultured cerebellar granule neurons (CGNs) in a dose dependent manner. Neuronal death was preceded by an increase in the reactive oxygen species (ROS) generation, as demonstrated using CellROX Green and MitoSOX Red. Confocal and electron microscopy showed that incubation with 0.05 mM TQ for 5 h induced changes in the intracellular localization of mitochondria and mitochondria hypertrophy and cell swelling. The antioxidant N-acetyl-L-cysteine (2 mM) protected CGNs from the toxic action of TQ. Taken together, these facts suggest that TQ is toxic for normal neurons, while ROS-induced changes in the mitochondria can be one of the major causes of the TQ-induced neuronal damage and death.
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Abbreviations
- CGN:
-
cerebellar granule neuron; NAC
- N:
-
acetyl-L-cysteine
- ROS:
-
reactive oxygen species
- TQ:
-
thymo-quinone.
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Compliance to ethical norms. All experimental protocols were approved by the Animal Ethics Committee of the Research Center of Neurology (Protocol registration no. 25/16) and were in accordance with the Council Directive 2010/63EU of the European Parliament and the Council of September 22, 2010 on the protection of animals used for scientific purposes.
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Published in Russian in Biokhimiya, 2020, Vol. 85, No. 2, pp. 239–247.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19-215, December 23, 2019.
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Stelmashook, E.V., Chetverikov, N.S., Golyshev, S.A. et al. Thymoquinone Induces Mitochondrial Damage and Death of Cerebellar Granule Neurons. Biochemistry Moscow 85, 205–212 (2020). https://doi.org/10.1134/S0006297920020078
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DOI: https://doi.org/10.1134/S0006297920020078