pregabalin and Reperfusion-Injury

The aim of this study was to investigate the efficacy of pregabalin on ischemia-reperfusion injuries.. Fifty-four patients were randomly assigned into 2 groups. A 150-mg tablet of pregabalin was given the night before and then 1 h before the operation for patients in Group P (pregabalin group, n = 27). A placebo was given to patients in Group C (control group, n = 27) at the same times. After combined spinal-epidural anesthesia was performed, venous blood samples were taken before tourniquet inflation (t1), just before tourniquet deflation (t2), and 20 min after tourniquet deflation (t3) for the analysis of total antioxidant status (TAS), total oxidant status (TOS), catalase (CAT), and ischemia-modified albumin (IMA).. There was no significant difference in TAS levels between the groups for the t3 period. However, the TAS in Group P was significantly higher in the t3 period than the t2 period (mean ± SD, 0.46 ± 0.1 vs. 0.38 ± 0.2 mmol of Trolox equivalent/L, respectively; P < 0.05). The CAT level in the t3 period was significantly higher in Group P than Group C (mean ± SD, 53.04 ± 32.1 vs. 35.46 ± 17.2 μmol/ formaldehyde, respectively; P < 0.05). In the t3 period, the TOS was significantly lower in Group P than Group C (mean ± SD, 11.97 ± 5 vs. 18.29 ± 9.9 pg/mL, respectively; P < 0.05). The TOS in Group P was significantly lower in the t3 period than the t2 period (mean ± SD, 11.97 ± 5 vs. 18.98 ± 10.7 pg/mL, respectively; P < 0.0001).. Pregabalin has no marked antioxidant activity, but it contributes to the antioxidant defense system of an organism.

Topics: Adult; Arthroplasty, Replacement, Knee; Catalase; Female; Humans; Male; Middle Aged; Pregabalin; Reperfusion Injury; Serum Albumin; Tourniquets

Ischemia-reperfusion injury is thought to be the most important factor affecting the success of liver surgery. Pregabalin has been studied to prevent ischemic reperfusion injury in many organs. The aim of this study was to investigate the role of pregabalin in preventing liver ischemic injury.. 40 male Wistar-Albino rats, 6-8 weeks old, were divided into 5 groups. Four groups other than the sham group were subjected to hepatic ischemia for 1 hour, followed by 2 hours of reperfusion. Effects of 30 mg/and 60 mg/kg pregabalin were evaluated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor α (TNF-α), nuclear factor-kappa B (NF-кB), interleukin (IL)-6 levels, measured in blood samples collected before and after ischemia. Apoptosis was measured by caspase-3, and tissue samples were evaluated for ischemia by histopathologic examination.. The 60 mg pregabalin group was significantly superior (p=0.024) to the N-acetylcysteine group and the 30 mg pregabalin group for AST levels (p=0.612 and p=0.807, respectively). The difference between before and after ischemia-reperfusion blood TNF-α levels was higher in the 60 mg pregabalin group, but not significantly different from the 30 mg pregabalin and N-acetylcysteine groups (p>0.05). Tissue TNF-α levels showed that 60 mg and 30 mg pregabalin treatment was more effective than no-treatment (p=0.011, p=0.033, respectively), but not superior to N-acetylcysteine (p>0.05).. It has been found that ischemia-reperfusion causes damage to the liver, and this damage may be irreversible if no treatment is given. Our study group, pregabalin molecule was found to be significantly effective in preventing ischemia-reperfusion injury and may have a therapeutic advantage over N-acetylcysteine.

Topics: Acetylcysteine; Alanine Transaminase; Analgesics; Animals; Aspartate Aminotransferases; Ischemia; Liver; Male; Pregabalin; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha

Progressive retinal ganglion cell (RGC) loss induced by retinal ischemia/reperfusion (RIR) injury leads to irreversible visual impairment. Pregabalin (PGB) is a promising drug for neurodegenerative diseases. However, with regard to RGC survival, its specific role and exact mechanism after RIR injury remain unclear. In this study, we sought to investigate whether PGB could protect RGCs from mitochondria-related apoptosis induced by RIR and explore the possible mechanisms.. C57BL/6J mice and primary RGCs were pretreated with PGB prior to ischemia/reperfusion modeling. The retinal structure and cell morphology were assessed by immunochemical assays and optical coherence tomography. CCK8 was used to assay cell viability, and an electroretinogram was performed to detect RGC function. Mitochondrial damage was assessed by a reactive oxygen species (ROS) assay kit and transmission electron microscopy. Western blot and immunofluorescence assays quantified the expression of proteins associated with the Akt/GSK3β/β-catenin pathway.. Treatment with PGB increased the viability of RGCs in vitro. Consistently, PGB preserved the normal thickness of the retina, upregulated Bcl-2, reduced the ratio of cleaved caspase-3/caspase-3 and the expression of Bax in vivo. Meanwhile, PGB improved mitochondrial structure and prevented excessive ROS production. Moreover, PGB restored the amplitudes of oscillatory potentials and photopic negative responses following RIR. The mechanisms underlying its neuroprotective effects were attributed to upregulation of the Akt/GSK3β/β-catenin pathway. However, PGB-mediated neuroprotection was suppressed when using MK2206 (an Akt inhibitor), whereas it was preserved when treated with TWS119 (a GSK3β inhibitor).. PGB exerts a protective effect against RGC apoptosis induced by RIR injury, mediated by the Akt/GSK3β/β-catenin pathway.

Topics: Animals; Apoptosis; beta Catenin; Caspase 3; Cell Survival; Glycogen Synthase Kinase 3 beta; Ischemia; Mice; Mice, Inbred C57BL; Pregabalin; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Reperfusion Injury; Retina; Retinal Ganglion Cells; Signal Transduction

Analgesic, anti-inflammatory and anti-apoptotic effects of pregabalin have been shown previously. In this study, we investigated the protective effect of different doses of pregabalin on skeletal muscle IR injury in rats.. 24 rats were randomly divided into 4 groups (Control, Ischaemia-Reperfusion (IR), IR-Pregabalin 50 mg, IR-Pregabalin 200 mg). Following IR, serum Ischemia Modified Albumin (IMA) and tissue Paraoxonase (PON) were studied and gastrocnemius muscle tissue was removed for histopathologic examination.. Interstitial inflammation was higher in the IR group than in the control and Pregabalin 200 mg groups (p = 0.037, p = 0.037, respectively). Congestion was higher in the IR group than in the control, Pregabalin 50 and 200 mg groups (p = 0.001, p = 0.004, p = 0.004, respectively). PON was lower in the IR group than in the Control, Pregabalin 50 and 200 mg groups (p = 0.001, p = 0.007, p = 0.015, respectively). IMA was higher in the IR group than in the Control, Pregabalin 50 and 200 mg groups (p < 0.0001, all).. We think that administration of pregabalin, more prominent at 200 mg, can reverse the injury that occurs in the skeletal muscle of IR-induced rats. Pregabalin can be safely used for analgesia in cases of IR (Tab. 2, Fig. 9, Ref. 41).

Topics: Animals; Apoptosis; Biomarkers; Disease Models, Animal; Male; Muscle, Skeletal; Oxidative Stress; Pregabalin; Rats; Rats, Wistar; Reperfusion Injury; Serum Albumin; Serum Albumin, Human

To evaluate the effect of pregabalin pre-treatment on spinal cord ischemia-reperfusion (I/R) injury and compare with methylprednisolone (MP).. Thirty-two rats were randomly divided into four groups as follow: Group 1 (sham)(n=8), group 2 (ischemia only)(n=8), group 3 (30 mg/kg pregabalin)(n=8), and group 4 (30 mg/kg methylprednisolone)(n=8). Laparotomy was performed without aortic clamp in the sham group. All animals were sacrificed 24 hours after surgery. The spinal cord tissue samples were harvested and caspase-3 activity, tumor necrosis factor-alpha (TNF-α) and Interleukin-1 Beta (IL-1β) levels, catalase (CAT) activity, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) levels malondialdehyde (MDA) levels and nitric oxide (NO) levels were analyzed to investigate the effects of different excitatory and inflammatory pathways in mechanism of I/R injury. Ultrastructural and histopathological examinations were carried out. Neurological recovery was measured by Basso, Beattie, Bresnahan (BBB) test and Inclined Plane Test.. Decresead caspase-3 activity and decreased inflammatory markers like TNF-α, IL-1β, and decresaed excitotatory pathways like CAT, GPx, MDA, NO and SOD were observed in both pregabalin pre-treatment and MP treatment groups. Pregabalin pre-treatment produced better ultrastructural results compared to MP treatment, as with histopathological examination. Pregabalin group showed better recovery compared to MP treament group according to BBB scoring system.. Pregabalin pre-treatmet and MP treatment both has neuroprotective effect on I/R injury by decreasing caspase dependant apoptosis, and inflammatory and oxidative stress markers. In addition, pregabalin pre-treatment had better clinical effects compared to MP treatment.

Topics: Animals; Apoptosis; Male; Methylprednisolone; Neuroprotective Agents; Oxidative Stress; Pregabalin; Rats; Reperfusion Injury; Spinal Cord Ischemia

Hyperglycemia, which reduces the efficacy of treatments and worsens clinical outcomes, is common in stroke. Ability of pregabalin to reduce neuroexcitotoxicity may provide protection against stroke, even under hyperglycemia. We investigated its protective effect against hyperglycemic stroke and its possible molecular mechanisms. Male Wistar rats administered dextrose to cause hyperglycemia, underwent middle cerebral artery occlusion for 1 h and subsequent reperfusion. Rats were treated with an intraperitoneal injection of 30 mg/kg pregabalin or an equal amount of normal saline at the onset of reperfusion (n = 16 per group). At 24 h after reperfusion, neurological deficit, infarct volume, and apoptotic cell count were assessed. Western blot analysis was performed to determine protein expression of high-mobility group box 1 (HMGB1), toll-like receptor-4 (TLR-4), phosphorylated nuclear factor-kappa B (p-NF-κB), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), phosphorylated inducible and endothelial nitric oxide synthase (p-iNOS, p-eNOS), Bcl-2, Bax, Cytochrome C, and caspase-3 in the brain. Pregabalin-treated rats showed significantly improved neurological function (31% decrease in score), reduced infarct size (by 33%), fewer apoptotic cells (by 63%), and lower expression levels of HMGB1, TLR4, p-NF-κB, IL-1β, and TNF- α, compared with control rats. Decreased p-iNOS and increased p-eNOS expressions were also observed. Expression of Bax, Cytochrome C, and cleaved caspase-3/caspase3 was significantly downregulated, while Bcl-2 expression was increased by pregabalin treatment. Pregabalin administration upon reperfusion decreased neuronal death and improved neurological function in hyperglycemic stroke rats. Cogent mechanisms would include attenuation of HMGB1/TLR-4-mediated inflammation and favorable modulation of the NOS.

Topics: Animals; Apoptosis; Brain; Brain Infarction; Cytokines; Disease Models, Animal; HMGB1 Protein; Hyperglycemia; Injections, Intraperitoneal; Male; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pregabalin; Rats; Rats, Wistar; Reperfusion Injury; Stroke; Toll-Like Receptor 4

Chronic post-ischemia pain was induced in anesthetized rats by placing a tourniquet at the ankle joint for 3 h, and removing it to allow reperfusion. The effectiveness of standard analgesic drugs to attenuate mechanical allodynia was assessed 2 and 7 days after ischemia/reperfusion. Only high doses of morphine, dexamethasone and pregabalin partially reduced mechanical allodynia 2 days post-ischemia/reperfusion, while other treatments (ibuprofen, acetaminophen, amitriptyline) were not effective. Furthermore, only the highest dose of pregabalin reduced mechanical allodynia 7 days post-ischemia/reperfusion. These results are consistent with findings that complex region pain syndrome-I pain is refractory to most standard analgesic treatments.

Topics: Amitriptyline; Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Hindlimb; Ischemia; Male; Morphine; Pain; Pain Measurement; Peripheral Nervous System Diseases; Physical Stimulation; Pregabalin; Rats; Rats, Long-Evans; Reflex Sympathetic Dystrophy; Regional Blood Flow; Reperfusion Injury