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Chemistry and pharmacology of analgesic indole alkaloids from the Rubiaceaous plant Mitragyna speciosa. The regulation of reactive oxygen species production during programmed cell death. The Journal of Cell Biology 141: 1423-1432. Cytochrome P450 2E1: its clinical and toxicological role.

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Mouse Lymphoma Thymidine Kinase Gene Mutation Assay. Van Engeland M. Annexin-V-affinity assay: A review on an apoptosis detection systembased on phosphatidylserine exposure.

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In this part of the study two initiator caspases maeng da kratom for pain caspases-8 and 9 and two executioner caspases 3 and 7 were used to investigate the mechanism of caspase activation in MSE and MIT induced cell death. In parallel caspase inhibitors were employed to confirm the outcome of the former assays. The caspase-8 and caspase-9 colorimetric assays purchased from Invitrogen U. IETD and LEHD respectively. These assays were carried out according to manufacturer instructions.

The subG1 phase has been proposed to be a population of apoptotic cells (Darzynkiewicz et al 1992). Effects of MSE on cell cycle distribution of HEK 293 cells after 24 and 48 hours

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of treatment. Histograms are representative of three replicates of experiments with similar results and analysed by Cellquest Pro software.

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The p53 protein level was found to be decreased in a dose-dependant manner especially at lower concentrations of MSE treatment for 24 hr as shown in fig. Further experiments were carried out to determine the time course of the down regulation or loss of p53 (Fig. MSE and control groups implying that this cell line expresses p53 protein and the lost of p53 protein seen at high doses was due to treatment effects.

This finding supports the suggestion that there is no overt evidence of cancer or tumour incidence upon consumptions of Mitragyna speciosa Korth leaves. Introduction Cytotoxicity and genotoxicity status of MSE and MIT were established in the previous chapters and both agents were determined to be toxic at high dose but not genotoxic. The molecular events leading to toxicity are yet to be fully understood.

Immunological Investigations 29: 51-60 Pellegata N. DNA damage and p53-mediated cell cycle arrest: A reevaluation. PNAS 93: 1520915214. In situ

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