The effect of ferulic acid on experimental traumatic brain damage in rats.

AIM: Traumatic brain injury is an important social health problem due to the fact that young adults are more likely to be affected, and advanced functional limitations are observed in survivors. In this study, we aimed to investigate the protective effect of ferulic acid in an experimental trauma model. MATERIAL AND METHODS: This study was performed in March 2016 at Dokuz Eylül University Experimental Animal Laboratory. Subjects were randomly divided into 4 groups Control, Ethyl Alcohol, Trauma, Trauma/Ferulic Acid groups. For histological findings, Cresyl violet; for immunohistochemical analysis, TUNEL and Active Caspase-3 staining were used. For biochemical analysis, Superoxide dismutase, Malondialdehyde, and Glutathione values ​​were examined. RESULTS: The application of ferulic acid has been shown to primarily reduce neuronal apoptosis, the levels of free radicals, and to effect oxidant/antioxidant balance positively by increasing the levels of antioxidants, such as Superoxide dismutase and Glutathione that are developed due to brain damage. Our study group has shown that ferulic acid decreased nerve tissue pathologies after generated brain trauma compared to injury groups. CONCLUSION: Addition of ferulic acid to the traditional head trauma treatment has the strength, and ability to increase the rate, and percentage of healing (Tab. 2, Fig. 4, Ref. 28).

The effects of α-lipoic acid on immature rats with traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality during childhood. TBI enhances formation of reactive oxygen species that cause neuron damage and apoptosis. α-Lipoic acid (LA) is a free radical scavenger and biological antioxidant. We investigated the effects of LA treatment on the parietal and prefrontal cortex, and on the hippocampal regions of the brain in 7-day-old rat pups that had been subjected to contusion injury. Forty-two male rats were divided randomly into a control group, a TBI group and a TBI + LA treated group. LA was administered 30 min after TBI through an intragastric tube once daily for 2 days. Forty-eight hours after TBI, the animals were sacrificed and tissues were examined for apoptosis and density of neurons. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and active caspase-3 immunostaining were used to detect apoptosis. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels also were measured. Histological evaluation showed that LA treatment significantly reduced TBI-induced neuronal death in the hippocampus, prefrontal and parietal cortex; TUNEL- and caspase-3-positive cells also were decreased in the same regions. In addition, LA administration increased GPx and SOD activity in the prefrontal cortex. It appears that LA may be beneficial for TBI in rats.

Carnosine attenuates oxidative stress and apoptosis in transient cerebral ischemia in rats.

Cerebral ischemia leads to cognitive decline and neuronal damage in the hippocampus. Reactive oxygen species (ROS) play an important role in the neuronal loss after cerebral ischemia and reperfusion injury. Carnosine has both antioxidant and neuroprotective effects against ROS. In the present study, the effects of carnosine on oxidative stress, apoptotic neuronal cell death and spatial memory following transient cerebral ischemia in rats were investigated. Transient ischemia was induced by occlusion of right common carotid artery of rats for 30 min and reperfusion for 24 h or 1 week. Rats received intraperitoneal injection of 250 mg/kg carnosine or saline 30 min prior to experiment. Determination of antioxidant enzyme activities was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed using an In Situ Cell Death Detection Kit. Carnosine treatment elicited a significant decrease in lipid peroxidation and increase in antioxidant enzyme activities in ischemic rat brains. The number of TUNEL-positive cells was decreased significantly in carnosine-treated group when compared with the ischemia-induction group. Carnosine treatment did not provide significant protection from ischemia induced deficits in spatial learning. The results show that carnosine is effective as a prophylactic treatment for brain tissue when it is administered before ischemia without affecting spatial memory.

Antioxidant and antiapoptotic activities of deprenyl and estradiol co-administration in aged rat kidney.

Aging is a progressive degeneration process in living organisms. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has antioxidant, antiapoptotic and neuroprotective effects. Estradiol is also a neuroprotective and antioxidant hormone. The objective of this study was to determine whether the antioxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat kidney. Wistar Albino female rats were divided into six groups as follows; young (3 months old) control, aged (24 months old) control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and sham. All rats except for the sham group were injected for 21 days. Determination of oxidative stress parameter was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining and caspase-3 immunohistochemistry were performed. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation relative to aged control and sham-injected rats. The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. Deprenyl and estradiol replacement attenuated age-related changes in renal morphology. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat kidney by decreasing oxidative stress.

The effect of TRAIL molecule on cell viability in in vitro beta cell culture.

Insulin-dependent diabetes mellitus (IDDM) is an organ-specific autoimmune disorder triggered by autoreactive T cells directed to pancreas beta-cell antigens. In this disorder, more than 90% of beta cells are destroyed. Cell death may be mediated via soluble or membrane-bound cell death ligands. One of these ligands may be tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-alpha superfamily. In the present study, we examined whether TRAIL had cytotoxic effects on adult rat pancreas beta cell cultures and INS1-E rat insulinoma cell line cultures or not. In this study, cell destruction models were built with TRAIL concentrations of 10, 100 and 1000 ng. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used for evaluating cell viability. It was detected that cell cultures with TRAIL added showed no differences statistically when compared with control cultures containing no toxic additions. These results showed that TRAIL did not have significant cytotoxic effects on pancreas beta cell culture and INS-1E rat insulinoma cell line cultures. Detection of the expression of TRAIL receptors and natural apoptosis inhibitor proteins will be favourable to investigate the resistance mechanisms to TRAIL-induced cell death in this cell culture system.

Deprenyl and the relationship between its effects on spatial memory, oxidant stress and hippocampal neurons in aged male rats.

Oxidative stress may play a major role in the aging process and associated cognitive decline. Therefore, antioxidant treatment may alleviate age-related impairment in spatial memory. Cognitive impairment could also involve the age-related morphological alterations of the hippocampal formation. The aim of this study was to examine the relationship between the effects of deprenyl, an irreversible monoamine-oxidase B inhibitor, on spatial memory by oxidant stress and on the total number of neurons in the hippocampus CA1 region of aged male rats. In this study, 24-month-old male rats were used. Rats were divided into control and experimental groups which received an injection of deprenyl for 21 days. Learning experiments were performed for six days in the Morris water maze. Spatial learning was significantly better in deprenyl-treated rats compared to saline-treated rats. Deprenyl treatment elicited a significant decrease of lipid peroxidation in the prefrontal cortex, striatum and hippocampus regions and a significant increase of glutathione peroxidase activity in the prefrontal cortex and hippocampus. It was observed that deprenyl had no effect on superoxide dismutase activity. The total number of neurons in the hippocampus CA1 region was significantly higher in the deprenyl group than in the control group. In conclusion, we demonstrated that deprenyl increases spatial memory performance in aged male rats and this increase may be related to suppression of lipid peroxidation and alleviation of the age-related decrease of the number of neurons in the hippocampus. The results of such studies may be useful in pharmacological alleviation of the aging process.

Erythrocyte membrane and cytoskeletal protein glycation and oxidation in short-term diabetic rabbits.

The objective of this study was to elucidate the glycation and oxidation processes in plasma and erythrocyte membrane proteins as well as the major erythrocyte cytoskeletal protein, spectrin, using a short-term experimental rabbit diabetes model. Diabetes was induced with a single-dose alloxan injection. Spectrin was purified from erythrocyte ghosts with selective solubilization followed by gel filtration chromatography techniques, and tested for purity using sodium dodecyl sulfate-poly-acrylamide gel electrophoresis. Glycation in plasma proteins was measured as fructosamine using the nitroblue tetrazolium method, and in erythrocyte membrane and purified spectrin, as ketoamine equivalents, by the hydrazine/phenylhydrazine method. Protein oxidation in plasma, erythrocyte membrane proteins, and purified spectrin was evaluated in terms of sulfhydryl oxidation, based on cis-dichlorodiammine platinum (II) binding. Carbonyl formation was also measured in plasma and membrane proteins. Sulfhydryl oxidation, carbonyl groups and glycated protein levels showed statistically significant differences between the diabetic and control groups for both the plasma and the erythrocyte membrane proteins. The cis-dichlorodiammine platinum (II) binding was significantly different in diabetic rabbit erythrocyte spectrin, while glycation was not significantly different for this protein. Our data clearly demonstrate that both protein glycation and oxidation are biochemical alterations occurring in diabetes, even of short duration.

Leukocyte activation, oxidant stress and red blood cell properties after acute, exhausting exercise in rats.

Red blood cell (RBC) mechanical alterations and oxidative damage were investigated after an acute exhausting exercise in rats, together with the leukocyte activation. The groups formed as follows. Control (C) (n = 9), group I (n = 9) and group II (n = 7) from which blood samples were collected 15 minutes and 24 hours respectively, after acute exercise. The rats were subjected to running at a speed of 17 m/min until exhaustion. The leukocyte phagocytic activity (LPA), RBC lipid peroxidation and RBC deformability were measured. LPA increased significantly after the exhausting exercise and prolonged till 24 hours (p = 0.0168). RBC membrane lipid peroxidation was gradually increased till 24 hours (p = 0.0297) and there was a significant correlation between LPA and RBC lipid peroxidation (r = 0.63, p = 0.015). There was a slight but significant decrease in mean corpuscular volume (MCV) (p = 0.0467) and increase in mean corpuscular hemoglobin concentration (MCHC) (p = 0.0458) suggesting a cellular dehydration after 24 hours. No significant alteration was detected in RBC deformability, assessed by the Cell Transit Analyzer (CTA) and thought that decreased MCV might have masked to determine the alterations in membrane mechanical properties in CTA. As a conclusion the results imply that activated leukocytes might play role in the RBC damage observed after exhausting exercise encouraging oxidative stress.

The effects of single dose of methamphetamine on lipid peroxidation levels in the rat striatum and prefrontal cortex.

The administration of methamphetamine to experimental animals results in damage to dopaminergic neurons. In the present study, we demonstrated that a single dose (15 mg/kg) of methamphetamine results in production of oxidative stress as demonstrated by increased thiobarbituric acid reactive substances levels in the rat striatum and prefrontal cortex. In conclusion, the results of present study provide further evidence in support of the notion that oxidative stress may play an important role in the methamphetamine-induced neurotoxicity.

The effect of skin transplantation on tumor growth in mice.

BACKGROUND: Skin allograft is an immunostimulant. Skin allograft activates effector arms of the immune system including the cytotoxic T lymphocytes, activated macrophages, and natural killer cells. These cells may be involved in the destruction of tumor cells. METHODS: Balb/c mice were divided into the study (n = 10) and control (n = 10) groups. Alloskin grafts 1 cm in diameter from the backs of Swiss albino mice were placed on the backs of balb/c mice (study group). The same size autoskin grafts from the backs of other balb/c mice were used for the control group. Fourteen days after grafting, we inoculated 1,000 Ehrlich ascites tumor cells intraperitoneally into both groups. Two days after tumor inoculation, we used secondary allografts and autografts (which were about 2 to 3 mm in diameter) for the same groups. We followed up graft survival and animal survival in both groups. RESULTS: All 10 of the autografted mice died between the 18th and 25th days owing to malignancy. In the allografted group, 2 mice died (1 on day 17 and the other on day 23). Allograft rejection had not occurred in these 2 mice at the time of their death. The other 8 mice in the same group rejected allograft, on average within 9 days (9+/-3, median 8). These 8 mice were alive and without apparent health problems during the 4 months of follow-up. CONCLUSION: Allo-skin graft rejection may help rejection of tumor cells and may be of use in immunotherapy of cancer.

Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum.

The administration of methamphetamine to experimental animals results in damage to nigrostriatal dopaminergic neurons. In the present study, we demonstrated that both the acute repeated and the chronic administration of methamphetamine causes an increase in thiobarbituric acid reactive substances, which are indicators of lipid peroxidation, and superoxide dismutase activity in the rat striatum. The results of present study strengthen the notion that reactive oxygen species may play an important role in the methamphetamine-induced neurotoxicity.

IgA nephropathy in mice following repeated administration of conjugated Haemophilus influenzae type B vaccine (PRP-T).

OBJECTIVE: In this study, the risk of IgA nephropathy in Swiss albino mice following the subcutaneous administration of conjugated Haemophilus influenzae type b vaccine (PRP-T), containing capsular polysaccharide of the organism (PRP) conjugated to tetanus protein (T), was evaluated. METHODS: Three treatment and corresponding control groups, each containing mice, were constituted and given 2, 4, 6 injections of 1/4 HD of PRP-T or placebo, respectively, at 2-week intervals. All mice in each treatment group were sacrificed two weeks from the last injection to examine sequential glomerular changes. RESULTS: The niceoscpic examination of renal tissues revealed mesangial proliferation (6/7; 85%) in the first group given 2 doses of vaccine; mesangial proliferation (5/7; 72%) and increase in matrix (7/7; 100%) in the second group given 4 doses; and mesangial proliferation (7/7; 100%), increase in matrix (7/7; 100%), IgA (7/7; 100%) and C3 (3/7; 42%) deposition within mesangium in the third group given 6 doses. No histopathological changes were detected in the renal tissues of any control mouse. When the experimental groups were compared statistically with their respective controls at the light microscopic level, mesangial proliferation in the first group (p: 0.0047), mesangial proliferation (p: 0.021) and increase in matrix (p: 0.001) in the second group, mesengial proliferation (p: 0.001) and increase in matrix (p: 0.001) in the third group were determined to be significantly different. When study and control groups were compared by immunofluorescence microscopy, only the third group revealed a statistically significant difference with respect to IgA deposition (p: 0.001). C3 deposition was also demonstrated in this group, but it was not significantly different (p: 0.192). However, in no instance was a control mouse found to have any form of immune deposition. CONCLUSION: We concluded that conjugated Haemophilus influenzae type b vaccine, given at two-week intervals to a total of six doses, caused secondary IgA nephropathy in mice.