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Chronic Opium Treatment Can Differentially Induce Brain and Liver Cells Apoptosis in Diabetic and Non-diabetic Male and Female Rats

By Majid Asiabanha, Gholamreza Asadikaram, Amir Rahnema, Mehdi Mahmoodi, Gholamhosein Hasanshahi, Mohammad Hashemi and Mohammad Khaksari


It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and diabetic opium-addicted brain and liver cells were significantly higher than the both normal and diabetic rats. In addition, we found that apoptosis in brain cells of opium-addicted and diabetic opium-addicted male rats were significantly higher than opium-addicted and diabetic opium-addicted female, whereas apoptosis in liver cells of opium-addicted and diabetic opium-addicted female rats were significantly higher than opium-addicted and diabetic opium-addicted male. Overall, these results indicate that opium probably plays an important role in brain and liver cells apoptosis, therefore, leading neurotoxicity and hepatotoxicity. These findings also in away possibly means that male brain cells are more susceptible than female and interestingly liver of females are more sensitive than males in induction of apoptosis by opium

Topics: Original Article
Publisher: The Korean Physiological Society and The Korean Society of Pharmacology
OAI identifier:
Provided by: PubMed Central

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  10. (2002). Opium and its alkaloids.
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  14. Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells.
  15. (2001). Efffect of noscapine, the antitussive opioid alkaloid, on bradykinin-induced smooth muscle contraction in the isolated ileum of the guinea-pig. Acta Physiol Hung.
  16. Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway. Anticancer Drugs.
  17. (2007). p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells. Cancer Res.
  18. (2002). Papaverine induces apoptosis in vascular endothelial and smooth muscle cells. Life Sci.
  19. (1994). Headspace constituents of opium. Planta Med.
  20. Induction of diabetes by streptozocin in rats.
  21. (2008). Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats. Exp Diabetes Res.
  22. (2005). Annual prevalence of drug abuse. Austria: Wold drug report,
  23. Hippocampal long-term potentiation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates.
  24. (2001). Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev.
  25. Su n g B,
  26. (2003). Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain. Naunyn Schmiedebergs Arch Pharmacol.
  27. Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons.
  28. Widespread but regionally specific effects of experimenter- versus self-administered morphine on dendritic spines in the nucleus accumbens, hippocampus, and neocortex of adult rats.
  29. Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways.
  30. Sexual dimorphism in superantigen shock involves elevated TNF-alpha and TNF-alpha induced hepatic apoptosis.
  31. Effect of morphine on cell-mediated immune responses of human lymphocytes against allogeneic malignant cells.
  32. Pathways to ischemic neuronal cell death: are sex differences relevant?
  33. Gender and the injured brain. Anesth Analg.
  34. (1998). Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation.
  35. (1994). Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Cell Growth Differ.
  36. Alkayed NJ. Mechanisms of gender-linked ischemic brain injury.
  37. R o b o tka H, To ld i J , Véc sei L. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders.
  38. (2008). Zh an g W, Li ZG, Kam iy a H. The effects of C-peptide on type 1 diabetic polyneuropathies and encephalopathy in the BB/Wor-rat. Exp Diabetes Res.
  39. Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications. Antioxid Redox Signal.
  40. Differential expression of metabolism-related genes in liver of diabetic obese rats.

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