Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

The Neuroprotective Effect of Syringic Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats

WOS: 000360847200026PubMed ID: 25903968Acute arterial occlusions via different vascular pathologies are the main causes of spinal cord ischemia. We investigated neuroprotective effects of syringic acid on spinal cord ischemia injury in rats. Rats were divided into four groups: (I) sham-operated control rats, (II) spinal cord ischemia group, (III) spinal cord ischemia group performed syringic acid, and (IV) spinal cord ischemia group performed methylprednisolone intraperitoneally. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. A significant decrease was seen in malondialdehyde levels in group III as compared to group II (P < 0.05). Besides these, nuclear respiratory factor-1 and superoxide dismutase activity of group III were significantly higher than group II (P < 0.05). In histopathological samples, when group III was compared with group II, there was a significant decrease in numbers of apoptotic neurons (P < 0.05). In immunohistochemical staining, BECN1 and caspase-3-immunopositive neurons were significantly decreased in group III compared with group II (P < 0.05). The neurological deficit scores of group III were significantly higher than group II at twenty-fourth hour of ischemia (P < 0.05). Our study revealed that syringic acid pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required for syringic acid to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future

The Neuroprotective Effect of Glycyrrhizic Acid on an Experimental Model of Focal Cerebral Ischemia in Rats

silan, coskun/0000-0002-8352-6571; Guven, Mustafa/0000-0001-8643-9775; Silan, Coskun/0000-0002-8352-6571WOS: 000357666000023PubMed: 25687639Cerebral ischemia is still one of the most important topics in neurosciences. Our study aimed to investigate the neuroprotective and anti-oxidant effects of glycyrrhizic acid on focal cerebral ischemia in rats. Twenty-four rats were divided equally into three groups. A middle cerebral artery occlusion model was performed in this study where sham and glycyrrhizic acid were administered intraperitoneally following middle cerebral artery occlusion. Group I was evaluated as control. Malondialdehyde (MDA), superoxide dismutase (SOD), and nuclear respiratory factor-1 (NRF1) levels were analyzed biochemically on the right cerebral hemisphere, while ischemic histopathological studies were completed to investigate the anti-oxidant status. Biochemical results showed that SOD and NRF1 levels were significantly increased in the glycyrrhizic acid group compared with the sham group while MDA levels were significantly decreased. on histopathological examination, cerebral edema, vacuolization, degeneration, and destruction of neurons were decreased in the glycyrrhizic acid group compared with the sham group. Cerebral ischemia was attenuated by glycyrrhizic acid administration. These observations indicate that glycyrrhizic acid may have potential as a therapeutic agent in cerebral ischemia by preventing oxidative stress

SDA, a DNA Aptamer Inhibiting E- and P-Selectin Mediated Adhesion of Cancer and Leukemia Cells, the First and Pivotal Step in Transendothelial Migration during Metastasis Formation

Endothelial (E-) and platelet (P-) selectin mediated adhesion of tumor cells to vascular endothelium is a pivotal step of hematogenous metastasis formation. Recent studies have demonstrated that selectin deficiency significantly reduces metastasis formation in vivo. We selected an E- and P-Selectin specific DNA Aptamer (SDA) via SELEX (Systematic Evolution of Ligands by EXponential enrichment) with a K (d) value of approximately 100 nM and the capability of inhibiting the interaction between selectin and its ligands. Employing human colorectal cancer (HT29) and leukemia (EOL-1) cell lines we could demonstrate an anti-adhesive effect for SDA in vitro. Under physiological shear stress conditions in a laminar flow adhesion assay, SDA inhibited dynamic tumor cell adhesion to immobilized E- or P-selectin. The stability of SDA for more than two hours allowed its application in cell-cell adhesion assays in cell culture medium. When adhesion of HT29 cells to TNFα-stimulated E-selectin presenting human pulmonary microvascular endothelial cells was analyzed, inhibition via SDA could be demonstrated as well. In conclusion, SDA is a potential new therapeutic agent that antagonizes selectin-mediated adhesion during metastasis formation in human malignancies

Genistein Exerts Neuroprotective Effect on Focal Cerebral Ischemia Injury in Rats

silan, coskun/0000-0002-8352-6571; Guven, Mustafa/0000-0001-8643-9775; Silan, Coskun/0000-0002-8352-6571WOS: 000354086100043PubMed: 25567369Brain ischemia and treatment are one of the important topics in neurological science. Free oxygen radicals and inflammation formed after ischemia are accepted as the most important causes of damage. Currently, there are studies on many chemopreventive agents to prevent cerebral ischemia damage. Our aim is to research the preventive effect of the active ingredient in genistein, previously unstudied, on oxidative damage in cerebral ischemia. Rats were randomly divided into three groups: control group (no medication or surgical procedure), ischemia group, and artery ischemia+genistein group, sacrificed at 24 h after ischemia. the harvested brain tissue from the right hemisphere was investigated histopathologically and for tissue biochemistry. Superoxide dismutase and nuclear respiratory factor 1 values decreased after ischemia and they increased after genistein treatment, while increased malondialdehyde levels after ischemia reduced after treatment. Apoptosis-related cysteine peptidase caspase-3 and caspase-9 values increased after ischemia, but reduced after treatment. Our study revealed that genistein treatment in cerebral ischemia reduced oxidative stress and neuronal degeneration. We believe that genistein treatment may be an alternative treatment method