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

다국어 초록 (Multilingual Abstract)

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.

참고문헌 (Reference)

1 Aneja R, "p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells" 67 : 3862-3870, 2007

2 Robinson TE, "Widespread but regionally specific effects of experimenter- versus self-administered morphine on dendritic spines in the nucleus accumbens, hippocampus, and neocortex of adult rats" 46 : 271-279, 2002

3 Sima AA, "The effects of C-peptide on type 1 diabetic polyneuropathies and encephalopathy in the BB/Wor-rat" 2008 : 230458-, 2008

4 Cunha-Oliveira T, "Street heroin induces mitochondrial dysfunction and apoptosis in rat cortical neurons" 101 : 543-554, 2007

5 Faulkner L, "Sexual dimorphism in superantigen shock involves elevated TNF-alpha and TNF-alpha induced hepatic apoptosis" 176 : 473-482, 2007

6 Kaul M, "Pathways to neuronal injury and apoptosis in HIV-associated dementia" 410 : 988-994, 2001

7 Lang JT, "Pathways to ischemic neuronal cell death: are sex differences relevant" 6 : 33-, 2008

8 Gao YJ, "Papaverine induces apoptosis in vascular endothelial and smooth muscle cells" 70 : 2675-2685, 2002

9 Karam GA, "Opium can differently alter blood glucose, sodium and potassium in male and female rats" 21 : 180-184, 2008

10 Schiff PL, "Opium and its alkaloids" 66 : 186-194, 2002

11 Ye K, "Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells" 95 : 1601-1606, 1998

12 Maneckjee R, "Opioids induce while nicotine suppresses apoptosis in human lung cancer cells" 5 : 1033-1040, 1994

13 Jaume M, "Opioid receptor blockade reduces Fas-induced hepatitis in mice" 40 : 1136-1143, 2004

14 Singhal P, "Opiates promote T cell apoptosis through JNK and caspase pathway" 493 : 127-135, 2001

15 Newcomb EW, "Noscapine induces apoptosis in human glioma cells by an apoptosis-inducing factor-dependent pathway" 19 : 553-563, 2008

16 Mao J, "Neuronal apoptosis associated with morphine tolerance: evidence for an opioid-induced neurotoxic mechanism" 22 : 7650-7661, 2002

17 Venturella VS, "Natural Product, In The Science and Practice of Pharmacy. 19th ed." Mack Publishing Company 400-402, 1995

18 Yin D, "Morphine promotes Jurkat cell apoptosis through pro-apoptotic FADD/P53 and anti-apoptotic PI3K/Akt/NF-kappaB pathways" 174 : 101-107, 2006

19 Hsiao PN, "Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways" 256 : 83-91, 2009

20 Emeterio EP, "Modulation of apoptosis in the mouse brain after morphine treatments and morphine withdrawal" 83 : 1352-1361, 2006

21 Garcia-Fuster MJ, "Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain" 368 : 421-431, 2003

22 Sas K, "Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders" 257 : 221-239, 2007

23 Liu M, "Mechanisms of gender-linked ischemic brain injury" 27 : 163-179, 2009

24 Akbarzadeh A, "Induction of diabetes by streptozocin in rats" 22 : 60-64, 2007

25 Asadikaram G, "Impact of opium on the serum levels of TGF-β in diabetic, addicted and addicted-diabetic rats" 7 : 186-192, 2010

26 Nishikawa T, "Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications" 9 : 343-353, 2007

27 Pu L, "Hippocampal long-term potentiation is reduced by chronic opiate treatment and can be restored by re-exposure to opiates" 22 : 1914-1921, 2002

28 Buchbauer G, "Headspace constituents of opium" 60 : 181-183, 1994

29 Vagnerova K, "Gender and the injured brain" 107 : 201-214, 2008

30 Jafari Anarkooli I, "Evaluation of Bcl-2 family gene expression and Caspase-3 activity in hippocampus STZ-induced diabetic rats" 2008 : 638467-, 2008

31 Mahmoudian M, "Efffect of noscapine, the antitussive opioid alkaloid, on bradykinin-induced smooth muscle contraction in the isolated ileum of the guinea-pig" 88 : 231-237, 2001

32 Karam GA, "Effects of opium addiction on some serum factors in addicts with non-insulin-dependent diabetes mellitus" 9 : 53-58, 2004

33 Fuggetta MP, "Effect of morphine on cell-mediated immune responses of human lymphocytes against allogeneic malignant cells" 24 : 255-263, 2005

34 서은희, "Differential Expression of Metabolism-related Genes in Liver of Diabetic Obese Rats" 대한약리학회 14 (14): 99-103, 2010

35 Hitosugi N, "Comparative analysis of apoptosisinducing activity of codeine and codeinone" 98 : 643-650, 2003

36 Sklair-Tavron L, "Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons" 93 : 11202-11207, 1996

37 Boronat MA, "Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain" 134 : 1263-1270, 2001

38 Williams JT, "Cellular and synaptic adaptations mediating opioid dependence" 81 : 299-343, 2001

39 Sastry PS, "Apoptosis and the nervous system" 74 : 1-20, 2000

40 Sueoka E, "Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-kappaB activation" 252 : 566-570, 1998

41 Chawla S, "Annual prevalence of drug abuse" Wold drug report, United Nations Publication, United Nations Office on Drugs and Crime Vienna 363-366, 2005