A new approach to prevent ischemia/reperfusion injury in a rat model: remote ischemic conditioning.

PURPOSE: To evaluate the effect of remote ischemic conditioning (RIC) on ovarian ischemia/reperfusion injury in a rat model. METHODS: A total of 36 Wistar albino rats with a body weight of 220-250 g were used for this study. Right adnexal torsion was performed for 180 min, and at the end of the period, the adnex was released and the abdomen was reclosed for 180 min for reperfusion. Torsion and detorsion procedures were applied to all rats except group 1 (sham, control). The right lower extremity was tied to perform remote tissue ischemia in groups 3, 4, 5, and 6. The goal of the procedure, which was purplish discoloration and pulselessness of the extremity, was maintained. After 5 min of ischemia, reperfusion was achieved for 5 min. Repeating this procedure 3 times was defined as hypoxia attacks (RIC). Retrieved ovaries were examined for tissue injury with biochemical, histopathologic, and immunohistochemical analysis. RESULTS: Unlike the control group, vascular congestion, hemorrhage, edema, and inflammatory cell infiltration were observed in group 2 (only I/R [ischemia/reperfusion]). In groups 3 (I/R + RIC), 4 (I/R + RIC), 5 (I/R + RIC), and 6 (I/R + RIC), edema and inflammatory cell infiltration were not observed. However, vascular congestion and hemorrhage that were detected in these groups were higher than in group 1 (Control) and less than in group 2 (I/R). The Caspase-3 Index was found to be increased in all groups compared to group 1 (P < .001). However, the increase in the RIC-performed groups was significantly less than in group 2. The apoptotic index, which was determined by the TUNEL, was also found to be increased in all groups compared to group 1 (P < .001). When the comparison was made in relation to group 2, the decrease of AI in RIC-performed groups was statistically significant, except the decrease in group 6 (P = .29). CONCLUSIONS: It is not clinically conceivable to prepare the tissue for pre-ischemia in ovarian torsion. However, the RIC application, which will be initiated if torsion is suspected when arrangements are made for surgery, might be a simple, effective, and inexpensive approach to prevent I/R injury in the clinic.

The BDNF-TrkB signaling pathway is partially involved in the neuroprotective effects of hydrogen sulfide in Parkinson's disease.

Recent studies have demonstrated that hydrogen sulfide (H2S) has a neuroprotective effect in neurodegenerative diseases. It is possible that this effect is supported by brain-derived neurotrophic factor (BDNF). Our aim is to examine the effects of H2S on neural damage in Parkinson's disease (PD) and to reveal the role of the BDNF-TrkB pathway in its possible effect. PD model was created with 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 breed male mice were randomly divided into six groups: control, K252a, MPTP, MPTP + K252a, MPTP + NaHS, and MPTP + NaHS + K252a. TrkB receptor antagonist K252a and sodium hydrosulfide (NaHS) as a H2S donor were administered intraperitoneally. An increase was observed in the motor behavior tests in MPTP group, but NaHS treatment shortened the time spent on the balance beam and pole tests. It was also noticed that the BDNF-pathway played a role in the shortening of this period. Mice that received NaHS were found to have less MPTP-induced cellular damage. A positive effect of BDNF was also detected in the protection of these neurons. BDNF levels in the SN were significantly increased in MPTP group, compared to control group. Tissue CBS levels decreased in the groups that received K252a, compared to MPTP group. The findings of the present study display that the BDNF-TrkB pathway partially plays a role in the protective effect of H2S in the experimental mouse model of PD. This effect is probably due to changes in intracellular signaling pathways, rather than TrkB receptor expression.

Variations in systemic biomarkers of oxidative/nitrosative stress and DNA damage before and during the consequent two cycles of chemotherapy in breast cancer patients.

BACKGROUND: Previous studies have suggested the importance of redox regulation in carcinogenesis. The aim of this study was to evaluate the prognostic role of altered redox homeostasis and oxidative DNA damage in patients with breast carcinoma before and during two cycles of chemotherapy. METHODS: This study included 30 patients whose serum samples were obtained on admission before treatment, and after the first and second cycles of chemotherapy, and 20 controls. We investigated serum total antioxidant status (TAS), thiobarbituric acid reacting substances (TBARS), total nitrite/nitrate (NOx), nitrotyrosine (NT), and 8-hydroxydeoxy-guanosine (8-OHdG), as well as antioxidant enzyme activities, such as glutathione peroxidase (GPx), glutathione reductase (GRx). RESULTS: TBARS, NOx, NT and 8-OHdG concentrations were significantly increased, while antioxidant enzyme activities and TAS were significantly decreased in patients when compared to controls. A concurrent increase in TBARS, NOx, NT, and 8-OHdG and a decrease in antioxidant enzyme activities and TAS were also seen after chemotherapy. No difference was observed in the second cycle of chemotherapy when compared with the first course. CONCLUSIONS: In conclusion, decreased activities of these antioxidant enzymes and low TAS concentrations observed in our study might be due to the depletion of the antioxidant defense system to combat the free radical storm produced by chemotherapy. We suggest that the increased 8-OHdG and other oxidative/nitrosative stress products that we have measured in breast cancer patients may be prognostic risk factors for the magnitude of oxidation in serum.

Balanced vs unbalanced crystalloid resuscitation in a near-fatal model of hemorrhagic shock and the effects on renal oxygenation, oxidative stress, and inflammation.

BACKGROUND: The aim of the present study was to test the hypothesis that balanced crystalloid resuscitation would be better for the kidney than unbalanced crystalloid resuscitation in a rat hemorrhagic shock model. METHODS: Male Wistar rats were randomly assigned to four groups (n=6/group): (1) time control; (2) hemorrhagic shock control; (3) hemorrhagic shock followed by unbalanced crystalloid resuscitation (0.9% NaCl); and (4) hemorrhagic shock followed by acetate and gluconate-balanced crystalloid resuscitation (Plasma Lyte). We tested the solutions for their effects on renal hemodynamics and microvascular oxygenation, strong-ion difference, systemic and renal markers of inflammation and oxidative stress including glycocalyx degradation as well as their effects on renal function. RESULTS: The main findings of our study were that: (1) both the balanced and unbalanced crystalloid solutions successfully restored the blood pressure, but renal blood flow was only recovered by the balanced solution although this did not lead to improved renal microvascular oxygenation; (2) while unbalanced crystalloid resuscitation induced hyperchloremia and worsened metabolic acidosis in hemorrhaged rats, balanced crystalloid resuscitation prevented hyperchloremia, restored the acid-base balance, and preserved the anion gap and strong ion difference in these animals; (3) in addition balanced crystalloid resuscitation significantly improved renal oxygen consumption (increased VO(2), decreased [Formula: see text] ); and (4) however neither balanced nor unbalanced crystalloid resuscitation could normalize systemic inflammation or oxidative stress. Functional immunohistochemistry biomarkers showed improvement in L-FABP in favor of balanced solutions in comparison to the hemorrhagic group although no such benefit was seen for renal tubular injury (measured by NGAL) by giving either unbalanced or balanced solutions. CONCLUSIONS: Although balanced crystalloid resuscitation seems superior to balanced crystalloid resuscitation in protecting the kidney after hemorrhagic shock and is certainly better than not applying fluid resuscitation, these solutions were not able to correct systemic inflammation or oxidative stress associated with hemorrhagic shock.

Expressions of some vital molecules: glioblastoma multiforme versus normal tissues.

OBJECTIVE: The aim of this study was to assess plasma and/or tissue levels of adhesion and apoptotic molecules, cytokines, nitric oxide metabolites, levels of lipid peroxidation, myeloperoxidase and superoxide dismutase in patients with glioblastoma multiforme and controls. METHODS: All the molecules were evaluated in 25 tumors and 30 controls: 15 were normal healthy subjects for plasma and 15 were normal brain tissues that were collected during autopsy. Commercially available kits for measurements were used. RESULTS: Superoxide dismutase was significantly lower in tumors, while all other molecules were significantly elevated compared to the controls (p=0.0001). Superoxide dismutase negatively correlated with plasma interleukin-1beta (p=0.04) and plasma Fas (p=0.016). Plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 correlated positively with plasma 3-nitrotyrosine (p=0.019) and nitrite/nitrate (p=0.019), respectively. Furthermore, plasma interleukin-1beta also positively correlated with plasma nitrite/nitrate (p=0.003). DISCUSSION: These results suggest that there is a complex relationship between pro- and anti-apoptotic molecules in glioblastoma multiforme pathogenesis. Thus, targeting multiple pathways with advanced chemotherapeutic agents or radiotheraupetic regimens following total resections might be helpful in patients with glioblastoma multiforme since preventing a single pathway does not seem to be reasonable.