If time had permitted the role of metabolism in activating MSE and MIT would have been an important area to pursue. Kratom Strain Info Mc Dade as part of a toxicological assessment genotoxic potential of a compound is important to characterise. A genotoxic agent is capable of causing DNA damage and if repair is unsuccessful it can lead
to further major problems such as carcinogenesis.
PTX)-sensitive inhibitory G protein (Gi) (Tegeder et al 2003). Thus this information poses the question of whether the opioid receptors mediating the biological activity of the Mitragyna speciosa Korth plant may also mediate the MSE and MIT induced toxicity or cell death. I therefore predicted that opiate receptor antagonists would protect against MSE and MIT induced cell death. MSE toxicity both in acute and longer term treatment. Thus it is suggested that apart from MIT there are other chemicals present in the leaves of Mitragyna specioa Korth contributing to the MSE cytotoxicity. A summary of the kratom effects euphoria cytotoxic events leading to MSE or MIT induced SH-SY5Y cell death as discussed above are shown in fig. Mechanisms of MSE and MIT induced SH-SY5Y cells arrest and cell death.
The basic toxicology data established in the previous chapter has informed us on the potential cytotoxicity of MSE and MIT on several human cell lines which generally shows cytotoxicity with high dose. The lethal effect of the extract and major alkaloid (MIT) on the cells examined prompted the question whether cell death was accompanied by DNA damage. DNA damage as a result of endogenous sources (cellular metabolic processes) or exogenous sources (environmental factors such as chemical insult) could lead to reversible or irreversible genetic Kratom Strain Info Mc Dade change. Based on the long term use of this plant by humans testing for its genotoxic potential using mammalian cells was thought to be more appropriate than conventional first tier testing for gene mutation in bacteria. In fact the primary first tier bacterial genetic toxicology assay the Ames Salmonella assay is incapable of detecting large scale deletion or recombination kratom legal high guy events of the mutations. Such events are more common in mammalian cell mutagenesis (Clive et al 1990). Mitchell et al 1997).
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Metabonomic studies using cell lines or urine from animal models or perhaps urine from humans exposed to this plant are also suggested. Analysis of this study is underway. Last but not least the stimulation effects of MSE and MIT at low doses is another potential area to be investigated as it Kratom Strain Info Mc Dade could prove to be of potential therapeutic values
- Wild-type p53 can induce p21 and apoptosis in neuroblastoma cells but the DNA damage-induced G1 checkpoint function is attenuated
- The subG1 phase is proposed to be an apoptotic population (Darzynkiewicz et al 1992) as cells with condensed DNA appeared to stain less with PI and will appear to the left of the G1 peak
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The mutant frequency value was determined from the derived number of mutant colonies in medium containing TFT and the number of colonies growing in nonTFT medium. The preliminary data on selection of dose range and final summary of the MLA results for the MSE and MIT are discussed below: 3. MLA for MSE As shown in table 3. This implies that the presence of S9 at these concentrations increase the metabolic activation of MSE to toxic derivatives which killed the majority of the cells.
In view of these findings it is likely that the involvement of other chemicals that are present in the MSE most probably explained why metabolic activation by S9 increased MSE toxicity. Interestingly whilst S9 did not potentiate MIT toxicity prolonged exposure of the cells to MIT did appear to induce dose-dependant toxicity. The reason for this is not entirely clear. In summary MSE and MIT do not appear to be genotoxic in MLA. This finding supports the suggestion that there is no overt evidence of cancer or tumour incidence upon consumptions of Mitragyna speciosa Korth leaves.
The cells were counted and 2 x 104 cells were transferred onto microscope slides followed by centrifugation (cytospin at 450 rpm for 5 minute). Y in phosphate buffer) for 5 seconds. The excess stain was then drained onto absorbent paper and the slides were transferred into basic solution dye (methylene blue in phosphate buffer) for another 5 seconds.
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PNAS 70: 782-786. Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection. PNAS 70: 2281-2285. Conjugation-dependant carcinogenicity and toxicity of foreign compounds Advances in Pharmacology 27: 1-512.