s-allylcysteine and Reperfusion-Injury

Garlic in different forms has antioxidant properties. These properties are shown to be due to the existence of compounds such as water soluble organosulfur compounds, S-allylcysteine and lipid soluble compounds like diallyl sulfide. The in vivo and in vitro ischemia reperfusion studies showed that prophylactic administration of aqueous garlic prior to ischemia reperfusion inhibit lipid peroxidation and prevent depletion in glutathione through its compounds that led to functional recovery. Its ability to inhibit neutrophil migration could suppress fibrosis formation. These preventive effects are seen in models that studied organs such as kidney and liver with functional recovery. Organ system specific activity such as angiotensin converting enzyme-inhibiting activity contributes to a cardioprotective and blood pressure lowering effect. Future studies should focus on post ischemia reperfusion administration of garlic to explore its rescue potential rather than prophylactic impact. Bench research findings should be translated into clinical use through human studies.

Topics: Allyl Compounds; Antioxidants; Brain Ischemia; Cysteine; Garlic; Glutathione; Humans; Kidney; Lipid Peroxidation; Liver; Myocardial Reperfusion Injury; Phytotherapy; Reperfusion Injury; Sulfides

During cerebral ischemia, energy restoration through the regulation of glucose transporters and antioxidant defense mechanisms is essential to maintain cell viability. Antioxidant therapy has been considered effective to attenuate brain damage; moreover, the regulation of transcription factors that positively regulate the expression of glucose transporters is associated with this therapy. Recently, it has been reported that the use of antioxidants such as S-allylcysteine (SAC), a component of aged garlic extract (AGE), improves survival in experimental models of cerebral ischemia.. The aim of this study was to determine the effect of AGE and SAC on the level of mRNA expression of the main neuronal glucose transporter (GLUT3) and the glutamate cysteine ligase catalytic subunit (GCLC) in rats with transient focal cerebral ischemia.. Cerebral ischemia was induced in male Wistar rats by middle cerebral artery occlusion (MCAO) for 2 h. The animals were sacrificed after different reperfusion times (0-48 h). Animals injected with AGE (360 mg/kg, intraperitoneally (i.p.)) and SAC (300 mg/kg, i.p.) at the beginning of reperfusion were sacrificed after 2 h. The mRNA expression level was analyzed in the fronto-parietal cortex using quantitative polymerase chain reaction (qPCR).. Two major increases in GLUT3 expression at 1 h and 24 h of reperfusion were found. Both treatments increased GLUT3 and GCLC mRNA levels in control and under ischemic/reperfusion injury animals.. This data suggests that SAC and AGE might induce neuroprotection, while controlling reactive oxygen species (ROS) levels, as indicated by the increase in GCLC expression, and regulating the energy content of the cell by increasing glucose transport mediated by GLUT3.

Topics: Animals; Antioxidants; Brain Ischemia; Cysteine; Garlic; Glucose Transport Proteins, Facilitative; Glutamate-Cysteine Ligase; Male; Neuroprotective Agents; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury

Retinal ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against retina ischemia/reperfusion injury.. In vivo, retinal ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating retinal ganglion cell-5 (RGC-5) with 500 μM H(2)O(2) for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches.. The retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The increased protein levels of HIF-1α, VEGF, and MMP-9 were also seen in RGC-5 cells subjected to defined oxidative stress. Of clinical importance, the ischemic/ischemic-like detrimental effects were concentration-dependently (least effect at 25 μM) and/or significantly (50 and/or 100 μM) blunted when SAC was applied 15 min before retinal ischemia or ischemic-like insult, respectively.. SAC would seem to protect against retinal ischemia by acting as an antioxidant and inhibiting the upregulation of HIF-1α, VEGF, and MMP-9.

Topics: Animals; Antioxidants; Cell Line; Cysteine; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Hypoxia-Inducible Factor 1, alpha Subunit; Intraocular Pressure; Ischemia; Matrix Metalloproteinase 9; Oxidative Stress; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reperfusion Injury; Retina; RNA, Messenger; Treatment Outcome; Vascular Endothelial Growth Factor A

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The present study examined the hypothesis that S-allyl cysteine (SAC), organosulfur compounds found in garlic extract, would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). To test this hypothesis, male Wistar rats were subjected to MCAO for 2 hours and 22-hour reperfusion. S-allyl cysteine was administered (100 mg/kg, b.wt.) intraperitoneally 30 minutes before the onset of ischemia and after the ischemia at the interval of 0, 6, and 12 hours. After 24 hours of reperfusion, rats were tested for neurobehavioral activities and were killed for the infarct volume, estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase). S-allyl cysteine treatment significantly reduced ischemic lesion volume, improved neurologic deficits, combated oxidative loads, and suppressed neuronal loss. Behavioral and biochemical alterations observed after MCAO were further associated with an increase in glial fibrillary acidic protein and inducible nitric oxide expression and were markedly inhibited by the treatment with SAC. The results suggest that SAC exhibits exuberant neuroprotective potential in rat ischemia/reperfusion model. Thus, this finding of SAC-induced adaptation to ischemic stress and inflammation could suggest a novel avenue for clinical intervention during ischemia and reperfusion.

Topics: Allium; Animals; Antioxidants; Behavior, Animal; Brain Ischemia; Cerebrum; Cysteine; Glial Fibrillary Acidic Protein; Infarction, Middle Cerebral Artery; Inflammation; Male; Nervous System Diseases; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury

Ischemic brain is highly vulnerable to free radicals mediated secondary neuronal damage especially mitochondrial dysfunctions. Present study investigated the neuroprotective effect of S-allyl L-cysteine (SAC), a water soluble compound from garlic, against cerebral ischemia/reperfusion (I/R)-induced mitochondrial dysfunctions in hippocampus (HIP). We used transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia. SAC (300 mg/kg) was given twice intraperitoneally: 15 min pre-occlusion and 2 h post-occlusion at the time of reperfusion. SAC significantly restored ATP content and the activity of mitochondrial respiratory complexes in SAC treated group which were severely altered in MCAO group. A marked decrease in calcium swelling was observed as a result of SAC treatment. Western blot analysis showed a marked decrease in cytochrome c release as a result of SAC treatment. The status of mitochondrial glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6-PD) was restored by SAC treatment with a significant decrease in mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) and H2O2 content. SAC significantly improved neurological deficits assessed by different scoring methods as compared to MCAO group. Also, the brain edema was significantly reduced. The findings of this study suggest the ability of SAC in functional preservation of ischemic neurovascular units and its therapeutic relevance in the treatment of ischemic stroke.

Topics: Animals; Blotting, Western; Brain Edema; Calcium; Cysteine; Cytochromes c; Electron Transport Chain Complex Proteins; Glutathione; Hippocampus; Hydrogen Peroxide; Infarction, Middle Cerebral Artery; Lipid Peroxidation; Male; Mitochondria; Motor Activity; Neuroprotective Agents; Protein Carbonylation; Rats; Rats, Wistar; Reperfusion Injury; Severity of Illness Index

The effect of the garlic-derived antioxidant S-allylcysteine (SAC) on renal injury and oxidative stress induced by ischemia and reperfusion (IR) was studied in this work. Rats were anesthetized and subjected to right nephrectomy; 15 min later ischemia was induced for a period of 40 min and then the rats were subjected to a reperfusion period of 6 h after which they were killed to obtain blood and the left kidney. SAC was given at a dose of 100 mg/kg 30 min before nephrectomy, 15 min before ischemia, immediately before reperfusion and 2 h after reperfusion. IR-induced renal injury was evident by the increase in blood urea nitrogen (BUN) and serum creatinine as well as by the renal structural damage which was assessed by histological analysis. IR-induced oxidative stress was evident by the increase in immunostaining with 4-hydroxy-2-nonenal (4-HNE). SAC treatment was able to ameliorate the increase in BUN and serum creatinine and to decrease the structural damage. This protective effect was associated with a decrease in the immunostaining for 4-HNE. It is concluded that the antioxidant properties of SAC are involved in its protective effect on renal ischemia and reperfusion injury.

Topics: Aldehydes; Animals; Antioxidants; Cysteine; Female; Garlic; Immunohistochemistry; Kidney; Kidney Diseases; Rats; Reperfusion Injury

The efficacy of S-allylcysteine (SAC) as a free radical scavenger was studied using rat brain ischemia models. In a middle cerebral artery occlusion model, preischemic administration of SAC had the following effects: it improved motor performance and memory impairment and reduced water content and the infarct size. In a transient global ischemia model, the time course of free radical (alkoxyl radical) formation as studied by electron paramagnetic resonance (EPR) spectroscopy and alpha-phenyl-N-tert-butylnitrone (PBN) was biphasic; the first peak occurred at 5 min and the second at 20 min after reperfusion. Although SAC did not attenuate the first peak, it did affect the second peak, which is related to lipid peroxidation. The lipid peroxidation as estimated by thiobarbituric acid reactive substances (TBARS) increased significantly at 20 min after reperfusion. SAC decreased TBARS to the levels found without ischemia. These results suggest that SAC could have beneficial effects in brain ischemia and that the major protective mechanism may be the inhibition of free radical-mediated lipid peroxidation.

Topics: Animals; Antioxidants; Cysteine; Disease Models, Animal; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Free Radicals; Ischemic Attack, Transient; Lipid Peroxidation; Male; Memory Disorders; Neurons; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thiobarbituric Acid Reactive Substances; Time Factors; Water