Objective: Cisplatin (DDP, cis-diamminedichloroplatinium II) is one of the most potent chemotherapeutic antitumor drugs, but is able to generate reactive oxygen species (ROS) and it also inhibits the activity of antioxidant enzymes in renal tissue. In the present study, we investigated the preventive effect of 100, 200 and 400 mg/kg b.w. doses of vitamin E (VE), and 25, 50, and 100 mg/kg b.w. doses of vitamin A (VA) combination on malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) levels and superoxide dismutase (SOD) activity in cisplatin-induced toxicity in rat kidneys. Our literature survey indicated a lack of any experimental study showing the beneficial effect of VA on cisplatin-induced MDA, NO, GSH and SOD changes. For this reason, we hoped that this study would provide a unique contribution in that respect. Materials and Methods: 59 Wistar rats (11 to replace prematurely lost animals) were used. 48 evaluable rats were divided into 8 groups (n = 6 in each group): control group, DDP alone (5 mg/kg b.w.) group, 3 VE combination treatment groups of VE100+DDP, VE200+DDP, and VE400+DDP, and 3 VA combination treatment groups of VA25+DDP, VA50+DDP, and VA100+DDP. Kidney MDA, GSH, NO levels and SOD activities were determined for the assessment of oxidant-antioxidant balance. Results: While in the DDP group the tissue levels of MDA and NO were found to be significantly higher than in the control group, GSH levels and SOD activities were significantly lower. MDA and NO levels were found to be significantly lower and GSH levels and SOD activities significantly higher in the VE200+DDP and VE400+ DDP groups when compared with the DDP alone group. MDA and NO levels were found to be significantly lower in the VA50+DDP and VA100+DDP groups when compared with the DDP alone group. However, identical comparisons with the DDP alone group showed significantly higher GSH levels and SOD activities in the VA25+DDP, VA50+DDP, and VA100+DDP groups. Among the VE100+ DDP, VE200+DDP, and VE400+DDP groups, and VA25+ DDP, VA50+DDP, and VA100+DDP groups, MDA and NO levels decreased and GSH levels and SOD activities increased steadily and significantly as the doses of VE and VA increased. Conclusion: These vitamins would be effective in protecting against cisplatin-induced tissue damage in rat kidneys. It is possible that the toxic effect of cisplatin is somehow minimized by a compensatory mechanism involving VE and VA via induction of antioxidant enzyme activities following intraperitoneal injection of DDP.
The present study was carried out to evaluate the role of vitamin A (VA) on the induction of chromosomal aberrations (CA) in rat bone marrow cells and to investigate its modulating effect on chromosomal damage induced by doxorubicin (DXR). Wistar rats were treated with VA (7.5, 15 and 30 microg/kg body wt) once a day for 2 days by gavage before injecting DXR (90 mg/kg body wt). Rats in the control group were treated with corresponding doses of water and olive oil. Animals treated with the medium dose of VA (15 microg/kg body wt) plus single dose of DXR presented a statistically significant reduction in total number of CA and in number of abnormal metaphases (P < 0.05). However, when compared with control and DXR groups, the low and high VA doses (7.5 and 30 microg/kg body wt) were found to be less efficient than the medium dose VA (15 microg/kg body wt) in terms of parameters analyzed. Furthermore, the high dose of VA group (30 microg/kg body wt) was found to be clastogenic (P < 0.05). This study concludes that the protective effect of VA against chromosome damage is dose dependent.
It is well accepted that there is mutual relation between glia-glia and glia-neuron in the central nervous system. In the present study, the authors aimed to evaluate the effect of microglia conditioned medium (MCM) on brain derived neurotrophic factor (BDNF) gene expression of astrocytes by quantitative real-time polymerase chain reaction (PCR). Real-time PCR is one of the most recent techniques for determination of gene expression. It is the first choice when sensitivity, specifity and cost effectiveness are concerned. The authors present, for the first time, the settings of real-time PCR for quantification of BDNF gene expression of rat strital astrocytes. Astrocytes that cultured- from the striatum were incubated with conditioned medium of either Zymosan A stiumulated or unstimulated microglia which were cultured from striatum and cortex of the rat pups. Our results have shown that incubation with stimulated striatal MCM induced BDNF gene expression of striatal astrocytes (1.33 fold) when compared to astrocytes treated with regular medium or unstimulated striatal MCM. We have also seen the similar effect with cortical MCM implying that effect of MCM does not change with regionally different microglia.
This investigation was undertaken in order to provide some explanation in chromosomal polymorphism which is widely observed among the members of genus Spalax and also, an attempt was made to elucidate the speciation in this genus. 47 specimens of the mole rat from lower Euphrates were studied; of these, 18 specimens, taken from the east of the river, namely from Sanhurfa, were identified as S. ehrenbergi kirgisorum. The remaining 29 specimens, collected from the west of river, namely Adtyaman and Gaziantep, were identified as Spalax ehrenbergi intermedius. By the analysis of the karyotype, two karyotypic forms of S.e. kirgisorum (2n =52, NF = 76 and 2n =54, NF = 76) were found. Similarly, two karyotypic forms of S.e. intermedius (2n =52, NF = 76 and 2n =56, NF = 90) were established. The phylogenie relations of the karyotypic forms and evolutionary relationship between subspecies were discussed.
Fat mass and obesity-associated protein is an enzyme that oxidatively demethylates DNA. Although there are numerous studies regarding the catalytic function of FTO, the overall existence or absence of FTO on cellular proteome has not been investigated. This study investigated the changes in the soluble proteome of 3T3-L1 cells upon expression of the WT and the mutant (R316Q) FTO proteins. Protein extracts prepared from 3T3-L1 cells expressing either the WT or the mutant FTO proteins were used in DIGE experiments. Analysis of the data revealed the number of spots matched to every member and there were 350 ± 20 spots with 30.5% overall mean coefficient of variation. Eleven regulated protein spots were excised from the gels and identified by MALDI-TOF/TOF. One of the identified proteins was heterogeneous nuclear ribonucleoprotein K, which displayed more than 2.6- and 3.7-fold increases in its abundance in the WT and the mutant FTO expressing cells, respectively. Western blot analysis validated these observations. This is the first study revealing the presence of a parallel increase in expressions of FTO and HNRNPK proteins. This increase may codictate the metabolic changes occurring in the cell and may attribute a significance to HNRNPK in FTO-associated transformations.
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