Effects of thymoquinone on neurotoxic rats induced by 3,4-methylenedioxymethamphetamine

• Main Authors: Nasir, Mohamad, Nor Hidayah, Abu Bakar, Nor Suliana, Mustafa, Liyana Hazwani, Mohd Adnan, Farah Aina, Md Fauzi
• Format: Conference or Workshop Item
• Language: English; English
• Published: 2019
• Subjects: Q Science (General); QD Chemistry; R Medicine (General)
• Online Access: http://eprints.unisza.edu.my/2538/1/FH03-FP-19-29535.pdf; http://eprints.unisza.edu.my/2538/2/FH03-FP-19-31405.pdf; http://eprints.unisza.edu.my/2538/
• Institution: Universiti Sultan Zainal Abidin

Aims/Background:Ecstasy (3, 4-methylenedioxymethamphetamine; MDMA) is a psychoactive substance that is associated with neurotoxicity. The MDMA exposure on human results in alteration of serotonin (5.1-m released by brain and leads to degeneration of neuronal cells in hippocampus. Although there are several treatments available on the effects of MDMA, but most of them are synthetic drugs. There is less study was done on the effects of natural compounds in MDMA-induced neurotoxicity. Hence, a natural active compound from a black seed of Nirlia sativa known as thymoquinone (TQ) was studied for its protective effect towards neurotoxicity in rat model. This study aimed to investigate the effects of TQ on MDMA-induced neurotoxicity based on 5-HT level, sign of anxiety, recognition memory and neuronal damage in rats.Methodology: The induction of MDMA neurotoxicity was done with two different dosages to stimulate 5-HT depletion (single oral administration of 20 mg/kg MDMA) and neuronal damage (one week i.p treatment of 10 mg/kg MDMA) on rats. The administration of TO into neurotoxic rats was carried out in male Sprague Dawley (n=24, 6 per group). TQ treated groups were administered with 40 mg/kg TQ once daily for one week. Anxiety test was subjected to a light-dark test and social interaction test. Cerebrospinal fluid was collected from the cisterna magna to determine the level of 5-HT by means of Enzyme-Link Immunosorbent Assay (ELISA). A novel object recognition test (NORT) was carried out to measure the memory performance of the rats followed by a histopathological assessment carried out in the hippocampal dentate gyrus by using haematoxylin & eosin (H&E) and Fluoro-Jade C fluorescein staining.Results: It showed that MDMA caused a significant depletion of 5-HT and neuronal damage when compared to the control (P5.0.05). On the other hand, TO prevented depletion of 5--HT and reduced anxiety after undergoing a 1-week treatment in MDMA+PQ group as Compared to the untreated MDMA group (P<_0.05). The histopathology analysis revealed a statistically significant increase in numbers of positive cells by Fluoro-Jade C following the effect of MDMA on neuronal damage (MDMA induced group) compared to control. Next, the TQ treatments observed in MprviA+Tia exhibited a decline in positive cells from Fluoro-Jade C. The index of recognition memory was found to be increased in MDMA+TQ compared to the MDMA alone.Conclusion: This study suggests that the neuronal damage inflicted by MDMA in a rat model has the potential to be treated by TQ.