Effect of resveratrol on chromosomal aberrations induced by doxorubicin in rat bone marrow cells.

This study investigated the effects of resveratrol (RES) on doxorubicin (DXR) induced rat bone marrow cell chromosome aberrations. RES, a polyphenolic compound, has attracted considerable attention because of its antioxidant and antimutagenic effects. DXR, a chemotherapeutic agent, is known to cause chromosomal aberrations in healthy cells in cancer patients. In this study, Wistar albino male rats were divided into 6 groups with 6 animals each. The control group received distilled water i.p. and the DXR group received an i.p. injection of doxorubicin (90mg/kgbw). For the 2 RES dose groups (12.5 and 25mg/kgbw, respectively), RES was injected i.p. 5 times during the 24h study period to coincide with the schedule for the DXR+RES groups. The DXR-RES groups received DXR (90mg/kgbw) and RES at either 12.5 or 25mg/kgbw, i.p. 30min before, concurrently, and then every 6h after DXR administration. Bone marrow collection was timed to coincide with 24h after DXR administration in all groups. RES administration alone did not induce any significant increase in frequency of chromosome aberrations or abnormal metaphases compared with controls (p>0.05) while DXR alone did (p<0.05). In the DXR-RES 12.5mg/kgbw group, frequency of chromosome aberrations and abnormal metaphases were slightly reduced compared to DXR alone, but this was not statistically significant. However, in the DXR-RES 25mg/kgbw group, RES resulted in a statistically significant reduction in the frequency of chromosome aberrations and abnormal metaphases compared to those induced by DXR alone (p<0.05). These results indicate that RES (25mg/kgbw) significantly reduces frequency of DXR induced chromosome damage in bone marrow cells.

Blood and tissue nitric oxide and malondialdehyde are prognostic indicators of localized prostate cancer.

OBJECTIVES: Our objective was to examine blood and tissue levels of nitric oxide (NO) and malondialdehyde (MDA), and their correlations with well-known prognostic indicators [total prostate-specific antigen (tPSA), %free/total PSA (%f/t PSA), pathological stage (pT), and Gleason sum] in patients who had radical retropubic prostatectomy (RRP) for localized prostate cancer (PCa) without metastasis. PATIENTS AND METHODS: Preoperatively 31 patients' bloods were obtained for determination of NO, MDA, fPSA, tPSA, and %f/tPSA ratios. Tissues were obtained from RRP specimens for determination of NO and MDA. Gleason sum was assigned for each patient, and pT was determined according to 2002 TNM staging system. pTs were as follows: 10 pT2a, 7 pT2b, 8 pT2c, 4 pT3a, and 2 pT3b. Gleason sum of the PCa in the RRP specimens was as follows: 5 in 1, 6 in 14, 7 in 14, and 9 in 2 patients. RESULTS: There were strong correlations between blood and tissue levels of NO (r=0.83, p<0.001) and MDA (r=0.63, p<0.001), between serum NO and plasma MDA (r=0.88, p<0.001), and finally between tissue NO and tissue MDA (r=0.83, p<0.001). There was also a significant (p<0.05) relationship between all well-known prognostic indicators of PCa (tPSA, %f/tPSA, Gleason sum, and pT) and blood and tissue NO and MDA levels, with single exception of correlation between tissue MDA and Gleason sum (p=0.073). CONCLUSION: Clinically appropriate correlations shown in this study indicates that NO and MDA may be used for prognostic assessment of localized PCa, especially if supported with other well-designed studies including higher number of patients through multi-institutional collaboration.

Effect of pentylenetetrazole and sound stimulation induced single and repeated convulsive seizures on the MDA, GSH and NO levels, and SOD activities in rat liver and kidney tissues.

OBJECTIVES: the aim of our study was to evaluate the activity of superoxide dismutase (SOD) and the levels of glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) in liver and kidney tissues in a rat model of convulsive seizure induced by single and repeated doses of pentylenetetrazole (PTZ) and sound stimulation with key ringing. MATERIALS AND METHODS: male Wistar adult rats (n=48), were used in the experiment. The animals were divided into six groups: (1) Single Seizure Control Group (SS-Control; n=8), (2) Repeated Seizures Control Group (RS-Control; n=8), (3) PTZ induced Single Seizure Group (SS-PTZ Group; n=8), (4) PTZ induced Repeated Seizures Group (RS- PTZ Group; n=8), (5) Key-Ringing Induced Single Seizure Group (SS-KEY Group; n=8), (6) Key-Ringing Induced Repeated Seizures Group (RS-KEY Group; n=8). Following injections rats were observed for seizure activity for 30 min. Animals were sacrificed 24h after induced seizure (single or last seizure) or saline administration. MDA, NO, GSH levels and SOD activities were determined in liver and kidney tissues. RESULTS: there was no significant difference between SS-Control and RS-Control groups, SS-PTZ and SS-KEY groups, and RS-PTZ and RS-KEY groups (p>0.05) in none of the examined 4 parameters in liver and kidney tissues. The liver and kidney levels of MDA and NO in SS-PTZ group were found to be significantly higher than the SS-Control group (p<0.05). In SS-KEY group, the liver and kidney levels of MDA and NO were found to be significantly higher and GSH levels were significantly lower than the SS-Control group (p<0.05). While liver and kidney levels of MDA in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p<0.05), liver and kidney GSH levels were significantly lower (p<0.05). The liver levels of NO in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p<0.05). Kidney SOD activities in RS-PTZ group and RS-KEY group were found to be significantly lower than the RS-Control group (p<0.05). When RS-PTZ group is compared with the SS-PTZ group, the liver SOD activity and kidney NO level were found to be significantly lower in the RS-PTZ group (p<0.05). While the liver NO level and GSH level in RS-KEY group were significantly higher than the SS-KEY group, SOD activity was significantly lower in the RS-KEY group (p<0.05). When RS-KEY group was compared with SS-KEY group, the kidney NO level and SOD activity were found to be significantly lower in the RS-KEY group (p<0.05). CONCLUSION: in conclusion, key-ringing or PTZ induced single and repeated seizures result in increased oxidative damage and lipid peroxidation, and decreased antioxidant defense mechanisms.

Protective effects of increasing vitamin E and a doses on cisplatin-induced oxidative damage to kidney tissue in rats.

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.

Protective effects of N-acetylcysteine on the peroxidative changes of rat lungs exposed to inhalation of thinners.

OBJECTIVE: Long-term inhalation of thinners may cause damage, both to the lungs and to other organ systems. It causes cellular damage via formation of reactive oxygen species. The lung is protected from oxidative stress by the glutathione (GSH) antioxidant system which can be augmented by the thiol drug, N-acetylcysteine (NAC). This study investigated the protective effect of NAC on peroxidative changes in rat lungs exposed to inhalation of thinners for 8 weeks. METHODOLOGY: Seventy-two male Wistar albino rats were used and divided into two groups: one group inhaled only thinners (TI), while the other inhaled TI plus NAC. Rats in the TI and TI + NAC groups were divided into four subgroups (each consisting of eight rats) according to the duration of exposure to TI: 2, 4, 6 and 8 weeks. A control group (n = 7) of rats inhaled neither TI nor NAC. Malondialdehyde (MDA) and GSH levels, and superoxide dismutase (SOD) activities were determined in the lung tissues. Histopathological findings were evaluated as acute and chronic changes in the alveoli and interstitium in the TI and TI + NAC groups and compared with those in the control group. RESULTS: While tissue MDA levels in the groups inhaling TI for 4, 6 and 8 weeks were significantly higher than those in the control groups (P < 0.01, P < 0.01, P < 0.0001, respectively), GSH levels were significantly lower (P < 0.05, P < 0.01, P < 0.01, respectively). Tissue SOD activities in the groups inhaling TI for 6 and 8 weeks were significantly lower than those in the control group (P < 0.05, P < 0.01, respectively). In the TI group, MDA levels were significantly increased (P < 0.01) with increasing duration of inhalation (from the second week through to the eighth week), while GSH levels and SOD activities were significantly decreased (P < 0.01, P < 0.01). Tissue MDA levels were significantly lower in the TI + NAC groups across all inhalation periods, when compared with the TI groups (P < 0.01, P < 0.0001, P < 0.0001, P < 0.0001, respectively). Tissue GSH levels in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.01, P < 0.01, P < 0.0001). Tissue SOD activities in the TI + NAC groups were significantly higher than those of the TI groups (respective values: P < 0.05, P < 0.0001, P < 0.05, P < 0.0001). Pathological examinations with light microscopy did not show any beneficial effect of NAC application in terms of deferring or alleviating the negative effects of TI. CONCLUSIONS: Thinners are agents that cause imbalance between oxidants and antioxidants produced by aerobic cellular systems. This imbalance between oxidant and antioxidant systems is decreased by the effect of NAC. However, ultrastructural studies may be needed to substantiate this evidence morphologically, as light microscopy was inconclusive.