AIM OF STUDY: To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell.
METHOD AND MATERIALS: Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR.
RESULT: Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of mitragynine while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only.
CONCLUSION: These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine.
MATERIALS AND METHODS: The effects of mitragynine on the mRNA and protein expression of COX-1 and COX-2 and the production of prostaglandin E(2) (PGE(2)) were investigated in LPS-treated RAW264.7 macrophage cells. Quantitative RT-PCR was used to assess the mRNA expression of COX-1 and COX-2. Protein expression of COX-1 and COX-2 were assessed using Western blot analysis and the level of PGE(2) production was quantified using Parameter™ PGE(2) Assay (R&D Systems).
RESULTS: Mitragynine produced a significant inhibition on the mRNA expression of COX-2 induced by LPS, in a dose dependent manner and this was followed by the reduction of PGE(2) production. On the other hand, the effects of mitragynine on COX-1 mRNA expression were found to be insignificant as compared to the control cells. However, the effect of mitragynine on COX-1 protein expression is dependent on concentration, with higher concentration of mitragynine producing a further reduction of COX-1 expression in LPS-treated cells.
CONCLUSIONS: These findings suggest that mitragynine suppressed PGE(2) production by inhibiting COX-2 expression in LPS-stimulated RAW264.7 macrophage cells. Mitragynine may be useful for the treatment of inflammatory conditions.
Data Sources and Methods: A retrospective study based on telephone calls reported on poisoning caused by pharmaceutical products undertaken by the National Poisoning Centre (NPC) in Penang (Malaysia) was used as the basis of this study covering the period between 2010 and 2015. The study included the mode and type of poisoning, exposure routes as well as the incidence locations.
Results: A total of 10,998 cases were examined, finding that females represented 5,899 cases (53.6%) being intoxicated more frequently compared to the number of males, 3,839 (34.9%). The age group of poisoning cases ranged between 20 and 29 years representing 2,579 (23.4%) of reported cases. The common mode of poisoning was attributed to suicide 5,203 (47.3%) from among the 10,998 cases and the highest poisoning agents reported were from the psychiatric group of pharmaceutical products of 2,287 (21%).
Conclusion and Implications: These findings indicate a rising trend of suicidal poisoning attempts between 2013 and 2015, which emphasizes the need for more stringent and effective enforcement protocols to limit the rising incidence of poisoning. As such, analyzing the trends in poisoning in a particular zone periodically could help health policy-makers to develop management policies and prevention strategies.
SETTING: Pesticide poisoning database of Malaysia National Poison Centre (NPC) from 2006 to 2015.
PARTICIPANTS: Telephone enquiries regarding pesticide poisoning were made by healthcare professionals. Information received by the NPC was entered into a retrievable database of standardised Poison Case Report Form, as adapted from the World Health Organization (WHO).
OUTCOMES: The outcome of the study is to provide an overview of national epidemiological profile of pesticide poisoning. High-risk groups of people and their circumstances were also identified to ensure that appropriate measures are strategised.
RESULTS: Within the study period, a total of 11 087 pesticide poisoning cases were recorded. Sixty per cent of these cases were intentional in nature and most were found among male individuals (57%) of the Indian race (36.4%) aged between 20 and 29 years (25.5%), which occurred at home (90%) through the route of ingestion (94%). The highest number of poisoning was due to herbicides (44%) followed by agricultural insecticides (34%), rodenticides (9.9%), household insecticides (9.5%) and fungicides (0.5%). In addition, 93.6% of intentional pesticide poisoning cases were caused by suicide attempts. The results of this study show that there was an increasing trend in pesticide poisoning incidents over the 10-year duration. This indicates that pesticide poisoning is a prevalent public health problem in Malaysia, resulting in an average incidence rate of 3.8 per 100 000 population.
CONCLUSIONS: Deliberate pesticide ingestion as a method of suicide has become a disturbing trend among Malaysians. Therefore, regulation of highly hazardous pesticides must be enforced to ensure controlled and limited access to these chemicals by the public.