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Effects of thymoquinone on neurotoxic rats induced by 3,4 methylenedioxymethamphetamine (MDMA)
xviii, 133leaves: illustration (some colour); 30cm.
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-HT) released by brain and leads to degeneration of neuronal cells in hippocampus. Most of the treatments available to treat the effects of MDMA are synthetic drugs that can cause severe side effects. An alternative medicine that has less side effects is suggested to treat neurotoxicity caused by MDMA. Thymoquinone (TQ), which is an active compound from Nigella sativa was studied for its protective effect towards nerotoxicity in various models. In spite of that, there is lack od scientific evidences on the effects of TQ in the model of MDMA-induced neorotoxicity. Hence, this study aimed to investigate the effects of TQ on MDMA-induced nerotoxicity based on 5-HT level, sign of anxiety, recognition memory and neuronal damage in rats. The induction of MDMA neurotoxicity was done with two different dosages to stimulate 5-HT depletion and neuronal damage on rats. The administration of TQ into MDMA-induced 5-HT depletion rats was carried out in male Sparaque Dawley via 1-week treatment dividing into four groups (n=32, 6-8 per group). The studies groups involved with the treatments comprise i) Control (1 mL/kg saline), ii) MDMA (single administration of 20 mg/kg MDMA), iii) MDMA-TQ (single administration of 20 mg/kg MDMA + 40 mg/kg TQ) and iv) TQ (40mg/kg TQ). 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). Meanwhile, the administration of TQ into MDMA-induced neuronal damage rats wa carried out in male Sparaque Dawley via 1-week treatment dividing into four groups ((n=32, 7-9 per group). The studied groups involved with the treatments comprise i) Control (1 mL/kg saline), ii) MDMA (10 mg/kg MDMA), iii) MDMA-TQ (10 mg/kg MDMA + 40 mg/kg TQ) and iv) TQ (40mg/kg TQ). A novel object recognition test (NORT) was carried out to measure the memory performance of the rats follwed by a histopathological assessment carried out in the hippocampal dentate gyrus by using two staining methods of haematoxylin & eosin (H&E) and Fluoro-Jade C fluorescein. It showed that MDMA caused a significant depletion of 5-HT and neronal damage when compared to the control (P<0.05). On the other hand, TQ prevented depletion of 5-Ht and reduced anxiety-like behaviours after undergoing a 1-week treatment in MDMA+TQ 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 neronal damage (MDMA induced group) compared to control. Next, the TQ treatments observed in MDMA+TQ exhibited a decline in positive cells from Fluoro-Jade C. The index of recognition memory was found to be increased in MDMA+TQ compraed to the MDMA alone. This study suggests that the neuronal damage inflicted by MDMA in a rat model has the potential to be treated by TQ.
1. Introduction -- 2. Literature Review -- 3. Materials and Methods -- 4. Result -- 5. Discussion -- 6. Conclusion
Thesis (Degree of Master of Science) - Universiti Sultan Zainal Abidin, 2020
Includes bibliographical references (leaves 100 - 119)