One of the most frequent complications of diabetes is diabetic peripheral neuropathy. Hyperglycemia would result in the advancement of this condition over a period of time. The most effective way in preventing diabetic neuropathy is regular control of glucose. In this study; we evaluated the effects of lithium onstreptozocin (STZ)-induced diabetic neuropathy in rats. Diabetic neuropathy was created 7 weeks after administration of STZ (45 mg/kg). Lithium was added to drinking water (450 mg/l) for 7 weeks and its plasma level after this period of time was 0. 17± 0. 02 mmol/l. Levels of ADENOSINE TRIPHOSPHATE (ATP) in dorsal root ganglion (DRG) neurons, oxidative stress parameters, open-field activity test and morphological analysis were assessed in this investigation. Currentresults showed significant elevation of oxidative stress biomarkers, reduction of ATP, abnormal morphology of DRG neurons and decrease of total distance moved in rats with STZ-induced diabetic neuropathy. The alterations in mentioned parameters were considerably restored by lithium treatment. These findings provide evidence for protective effects of lithium on STZinduced diabetic neuropathy.

Background and aim: ADENOSINE 5-TRIPHOSPHATE (ATP) is not only the current energy sources for all cells but also plays a critical role in triggering signaling pathways leading to apoptosis or differentiation. During the past years many investigations have been reported the anti-cancer activity of ATP on different cell lines. Also several mechanisms have been proposed for its action and it appears that its mechanism of action depends on the cell type. In the present study effects of ATP on human leukemia K562 cell line as an experimental model of CML and it mechanism of action were studied.Materials and Methods: K562 cells were cultured and treated with different concentrations of ATP (50-1000 mM) at various time intervals (24-72 h). Effect of ATP on cell proliferation was studied by MTT assay. Apoptosis was studied by flow cytometry and DNA fragmentation assay. Cell cycle and DNA contents were analyzed by flow cytometry. To evaluate the mechanism of action of ATP, effects of ATPgS (an undegradable agonist of ATP) and products of ATP degradation such as AMP, ADP and ADENOSINE were studied.Results: ATP with doses of 100-1000 mM inhibited growth of the cells and induced S-phase cell cycle arrest at the time intervals of 24-72 hour. These effects of ATP led to cell death by apoptosis. In addition, the results showed that these effects of ATP were through its degradation to ADENOSINE and eventually induction of pyrimidine starvation.Conclusion: Because current CML therapy methods which are based on chemotherapy are not very effective and have side effects such as drug resistance, ATP can be proposed as an effective compound alone or in combination with other drugs for treatment of CML.

Introduction: Leukemia is a heterogeneous malignant disease in which progression at the level of CD34+ cells has a major impact in drug resistance and relapse. The multi-drug resistance gene product, P-glycoprotein is an inhibitor of apoptosis proteins (IAPs), such as Survivin that are expressed simultaneously with several putative drug resistance parameters in CD34+ leukemia cells. In fact, IAPs over-expression and their anti-apoptotic splice variants are associated with CD34 positivity, poor response to chemotherapy and reduced overall survival in leukemic patients. Recently, ADENOSINE 5ʹ-TRIPHOSPHATE (ATP) has been reported to inhibit proliferation and induce apoptosis in several human cell lines. The K562 CD34+ human myeloid leukemia cell line has the unique feature of expressing significant functional IAPs and other drug-resistance genes. Thus, the efficacy of ATP in overcoming the resistance and expression profile of Survivin and its splice variants were examined in K562 cells in the present study.Methods: K562 cell were cultured and treated several times with different concentrations of ATP. Apoptosis was studied by fluorescent microscopy (Ao/EtBr double staining) and DNA fragmentation assay. The expression level of Survivin and its splice variants was studied by semiquantative RT-PCR method.Results: The results showed that over-expression of Survivin and its anti-apoptotic splice variant, 3b splice variant were decreased after treatment by ATP in a time- and dose-dependent manner. The expression levels of other splice variants (ΔEx3, 2b, 2a and 3a) did not show significant difference between the control and the treated cells.Conclusion: The results showed that ATP attenuated expression of Survivin and its anti-apoptotic splice variant, meaning that this nucleotide can facilitate apoptosis in drug-resistant leukemia cells. In addition, combination of ATP with standard chemotherapies may be utilized for inhibition of drug-resistance in leukemia cells.

Background: The mitochondria are an important source of ADENOSINE TRIPHOSPHATE (ATP) production in preimplantation embryo. Therefore, the objective of this study was to investigate the effect of vitrification and in vitro culture of mouse embryos on their mitochondrial distribution and ATP content.Methods: The embryos at 2-PN, 4- cell and blastocyst stages were collected from the oviduct of stimulated pregnant mice and uterine horns. Then, the embryos were vitrified with the cryotop method using ethylene glycol and dimethylsulphoxide. After evaluating the survival rates of vitrified embryos, their development to hatching stages were assessed. The ATP content of collected in vivo and in vitro embryos at different stages was measured by luciferin-luciferase bioluminescence assay. The distribution of mitochondria was studied using Mito-tracker green staining under a fluorescent microscope.Results: The survival rates of vitrified embryos at 2-PN, 4-cell and early blastocyst stages were 84.3, 87.87 and 89.89%, respectively. The hatching rates in previous developmental stages in vitrified group were 57.44, 66.73 and 70.89% and in non-vitrified group were 66.32, 73.25 and 75.89%, respectively (P>0.05). The ATP content of in vivo or in vitro collected embryos was not significantly different in both vitrified and non-vitrified groups (P>0.05). Mitochondrial distribution of vitrified and non-vitrified 2-PN embryos was similar, but some clampings or large aggregation of mitochondria within the vitrified 4-cell embryos was prominent. Conclusions: Vitrification method did not affect the mouse embryo ATP content. Also, the cellular stress was not induced by this procedure and the safety of vitrification was shown.