Vitexin Mitigates Haloperidol-Induced Orofacial Dyskinesia in Rats through Activation of the Nrf2 Pathway.

Vitexin (VTX), a C-glycosylated flavone found in various medicinal herbs, is known for its antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the protective effects of VTX against orofacial dyskinesia (OD) in rats, induced by haloperidol (HPD), along with the neuroprotective mechanisms underlying these effects. OD was induced by administering HPD (1 mg/kg i.p.) to rats for 21 days, which led to an increase in the frequency of vacuous chewing movements (VCMs) and tongue protrusion (TP). VTX (10 and 30 mg/kg) was given intraperitoneally 60 min after each HPD injection during the same period. On the 21st day, following assessments of OD, the rats were sacrificed, and nitrosative and oxidative stress, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptosis markers in the striatum were measured. HPD effectively induced OD, while VTX significantly reduced HPD-induced OD, decreased oxidative stress, enhanced antioxidant capacity, prevented mitochondrial dysfunction, and reduced neuroinflammatory and apoptotic markers in the striatum, and the protective effects of VTX on both behavioral and biochemical aspects of HPD-induced OD were significantly reduced when trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated pathway, was administered. These findings suggest that VTX provides neuroprotection against HPD-induced OD, potentially through the Nrf2 pathway, indicating its potential as a therapeutic candidate for the prevention or treatment of tardive dyskinesia (TD) in clinical settings. However, further detailed research is required to confirm these preclinical findings and fully elucidate VTX's therapeutic potential in human studies.

Evaluation of radiolabeled acetylcholine synthesis and release in rat striatum.

Cholinergic transmission underlies higher brain functions such as cognition and movement. To elucidate the process whereby acetylcholine (ACh) release is maintained and regulated in the central nervous system, uptake of [3 H]choline and subsequent synthesis and release of [3 H]ACh were investigated in rat striatal segments. Incubation with [3 H]choline elicited efficient uptake via high-affinity choline transporter-1, resulting in accumulation of [3 H]choline and [3 H]ACh. However, following inhibition of ACh esterase (AChE), incubation with [3 H]choline led predominantly to the accumulation of [3 H]ACh. Electrical stimulation and KCl depolarization selectively released [3 H]ACh but not [3 H]choline. [3 H]ACh release gradually declined upon repetitive stimulation, whereas the release was reproducible under inhibition of AChE. [3 H]ACh release was abolished after treatment with vesamicol, an inhibitor of vesicular ACh transporter. These results suggest that releasable ACh is continually replenished from the cytosol to releasable pools of cholinergic vesicles to maintain cholinergic transmission. [3 H]ACh release evoked by electrical stimulation was abolished by tetrodotoxin, but that induced by KCl was largely resistant. ACh release was Ca2+ dependent and exhibited slightly different sensitivities to N- and P-type Ca2+ channel toxins (ω-conotoxin GVIA and ω-agatoxin IVA, respectively) between both stimuli. [3 H]ACh release was negatively regulated by M2 muscarinic and D2 dopaminergic receptors. The present results suggest that inhibition of AChE within cholinergic neurons and of presynaptic negative regulation of ACh release contributes to maintenance and facilitation of cholinergic transmission, providing a potentially useful clue for the development of therapies for cholinergic dysfunction-associated disorders, in addition to inhibition of synaptic cleft AChE.

Neuroprotective effect of l-theanine in a rat model of chronic constriction injury of sciatic nerve-induced neuropathic pain.

BACKGROUND/PURPOSE: We investigated the protective efficacy of l-theanine (LT), the major amino acid components of green tea, on chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain (NP) development and neuronal functional changes in rats. METHODS: Rats with NP induced by CCI of the left sciatic nerve and sham-operated rats received LT or saline solution, with pain sensitive tests of thermal hyperalgesia and mechanical allodynia. Motor and sensory nerve conduction velocities were measured after surgery. Subsequently, the rats were sacrificed; the sciatic nerve was excised, homogenized, prepared and subjected for estimation of nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), myeloperoxidase (MPO), and caspase-3. RESULTS: CCI produced a significant increase in hyperalgesia and allodynia, an increase in SFI, a decrease in nerve conduction velocity, increases in NO, MDA, TNF-α, IL-1ß, IL-6, MPO, and caspase-3 levels, as well as reduction of GSH, SOD, and CAT in the rat sciatic nerve. LT treatment significantly and dose-dependently alleviated CCI-induced nociceptive pain thresholds and ameliorated abnormal nerve conduction and functional loss in rats with CCI. Moreover, LT treatment reduced NO and MDA levels, increased antioxidative strength, and markedly suppressed the levels of neuroinflammatory and apoptotic markers in injured sciatic nerves. CONCLUSION: This is the first report on the ameliorative effect of LT in CCI-induced NP in rats. This effect might be attributed to its anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective, thus making it potentially useful as an adjuvant to conventional treatment.

l-Theanine improves functional recovery after traumatic spinal cord injury in rats.

BACKGROUND/PURPOSE: Spinal cord injury (SCI) is a devastating medical condition for which no effective pharmacological interventions exist. l-Theanine (LT), a major amino acid component of green tea, exhibits potent antioxidative and anti-inflammatory activities and protects against various neural injuries. Here, we evaluated the potential therapeutic effects of LT on the recovery of behavioral motor functions after SCI in rats and the underlying neuroprotective mechanisms. METHODS: SCI was induced by applying vascular clips to the dura through a four-level T5-T8 laminectomy, and saline or LT (10/30 mg/kg) was intrathecally administered at 1-, 6-, and 24-h post-SCI. At 72-h post-SCI, half of the rats from each group for each parameter were sacrificed, and their spinal cord was excised for measurement of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase, catalase, tumor necrosis factor-α, interleukin-1ß/-6, myeloperoxidase, and caspase-3. The remaining rats from each group were subjected to Bresnahan locomotor-rating scale (BBB), inclined-plane, toe-spread, and hindfoot bar-grab tests at 1-, 4-, 7-, 10-, and 14-days post-SCI. RESULTS: LT treatment reduced NO and MDA levels, increased antioxidative strength, and markedly suppressed the levels of neuroinflammatory and apoptotic markers in the spinal cord after SCI. Moreover, LT treatment drastically promoted the recovery of behavioral motor functions post-SCI. CONCLUSION: Our findings revealed that LT can enhance the recovery of behavioral motor functions after SCI in rats, which related to the suppression of post-traumatic oxidative response, neural inflammation, and apoptosis. This evidence indicates that LT holds considerable potential for use in the clinical treatment/prevention of SCI-induced motor dysfunction.

Possible nitric oxide mechanism involved in the protective effect of L-theanine on haloperidol-induced orofacial dyskinesia.

Having powerful antioxidative properties, L-theanine (LT), one of the major amino acid components in green tea, has potent anti-oxidative and neuroprotective effects. In this study, we examined the potential protective effects of LT on haloperidol (HAL)-induced orofacial dyskinesia (OD) in rats. HAL treatment (1 mg/kg intraperitoneally for 21 days) induced OD; significant increases (P < 0.001) in the frequency of vacuous chewing movement and tongue protrusion as well as the duration of facial twitching. LT treatment (100 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation production and nitric oxide (NO) level, and enhance the antioxidation power in striatum from rats with HAL treatment. In order to examine the implication of NO pathway activity in HAL treatment, either NO precursor (L-arginine) or NO synthase inhibitor (L-NAME) was co-pretreated with LT; NO precursor treatment eliminated the protective effect of LT, in contrast to that NO synthase inhibitor treatment significantly potentiated the LT effects on behavioral and biochemical protection in HAL-treated rats. These results suggested that the NO pathway was implicated, at least in part, in the HAL-induced OD, as well as in the protective effect of LT in treating HAL-induced OD. The above evidence provides a clinically relevant value for LT in delaying or treating tardive dyskinesia.

Protective Effect of L-Theanine on Haloperidol-Induced Orofacial.

Tardive dyskinesia (TD) is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia (OD). Haloperidol (HAL)- induced OD has been widely used as an animal model to study the neuropathophysiology of human TD with its pathophysiology strongly associated with striatal oxidative stress. L-Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative effects and is able to protect against various oxidative injuries. In this study, we examined the potential protective effects of LT on HAL-induced behavioral and neurochemical dysfunction in rats. HAL treatment (1 mg/kg i.p. for 21 days) induced significant increases (P < 0.001) in the frequency of vacuous chewing movement (VCM) and tongue protrusion (TP) as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation (LPO) production, and enhance the antioxidation power in striatum from rats with HAL treatment. The above results indicate that LT has a protective role against HAL-induced OD, probably via its powerful antioxidative properties. Thus, LT may have a clinically relevant therapeutic effect in delaying or treating TD.

(-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats.

Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.

Neuroprotective Potentials of Berberine in Rotenone-Induced Parkinson's Disease-like Motor Symptoms in Rats.

Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative stress, mitochondrial dysfunction, and changes in neural structure. This makes RTN a valuable model for PD research. Berberine (BBR), an isoquinoline alkaloid recognized for its antioxidative, anti-inflammatory, and neuroprotective properties, was evaluated for its ability to counteract RTN-induced impairments. Rats received subcutaneous RTN at 0.5 mg/kg for 21 days, resulting in weight loss and significant motor deficits assessed through open-field, bar catalepsy, beam-crossing, rotarod, and grip strength tests. BBR, administered orally at 30 or 100 mg/kg doses, one hour prior to RTN exposure for the same duration, effectively mitigated many of the RTN-induced motor impairments. Furthermore, BBR treatment reduced RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, bolstered antioxidative capacity, enhanced mitochondrial enzyme activities (e.g., succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC)), and diminished striatal neuroinflammation and apoptosis markers. Notably, the co-administration of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly attenuated BBR's protective effects, indicating that BBR's neuroprotective actions are mediated via the Nrf2 pathway. These results underscore BBR's potential in ameliorating motor impairments akin to PD, suggesting its promise in potentially delaying or managing PD symptoms. Further research is warranted to translate these preclinical findings into clinical settings, enhancing our comprehension of BBR's therapeutic prospects in PD.

Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats.

With its pathophysiological characteristics strongly similar to patients with tardive dyskinesia (TD), haloperidol (HP)-induced neurotoxicity and orofacial dyskinesia (OD) in animal models have long been used to study human TD. This study aimed to explore the potential protective effects of betaine (BT), a vital biochemical compound present in plants, microorganisms, animals, and various dietary sources. The study focused on investigating the impact of BT on haloperidol (HP)-induced orofacial dyskinesia (OD) in rats, as well as the underlying neuroprotective mechanisms. To induce the development of OD, which is characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), rats were administered HP (1 mg/kg i.p.) for 21 consecutive days. BT was administered intraperitoneally (i.p.) at doses of 30 and 100 mg/kg, 60 min later, for 21 successive days. On the 21st day, after evaluating OD behavior, the rats were sacrificed, and various measurements were taken to assess the nitrosative and oxidative status, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptotic markers in the striatum. The results demonstrated that (1) HP induced OD development, and (2) BT was found to prevent most of the HP-induced OD; decrease oxidative stress levels; increase anti-oxidation power; prevent mitochondrial dysfunction; and reduce the levels of neuroinflammatory and apoptotic markers in the striatum. Our results demonstrate that the neuroprotective effects of BT against HP-induced OD are credited to its antioxidant prevention of mitochondrial dysfunction, anti-neuroinflammatory effects, and anti-apoptotic effects, suggesting that BT may be a novel therapeutic candidate in delaying or treating human TD in clinical settings. However, further studies will be warranted to extrapolate preclinical findings into clinical studies for a better understanding of the role of BT.

Through Its Powerful Antioxidative Properties, L-Theanine Ameliorates Vincristine-Induced Neuropathy in Rats.

L-theanine (LT), which is a major amino acid found in green tea, was shown to alleviate Vincristine (VCR)-induced peripheral neuropathy and associated neuronal functional changes in rats. To induce peripheral neuropathy, rats were administered VCR at a dose of 100 mg/kg/day intraperitoneally on days 1-5 and 8-12, while control rats received LT at doses of 30, 100, and 300 mg/kg/day intraperitoneally for 21 days or saline solution. Electrophysiological measurements were taken to evaluate the nerve functional loss and recovery through motor and sensory nerve conduction velocities. The sciatic nerve was examined for several biomarkers, including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total calcium, IL-6, IL-10, MPO, and caspase-3. The results showed that VCR caused significant hyperalgesia and allodynia in rats; decreased nerve conduction velocity; increased NO and MDA levels; and decreased GSH, SOD, CAT, and IL-10 levels. LT was found to significantly reduce VCR-induced nociceptive pain thresholds, decrease oxidative stress levels (NO, MDA), increase antioxidative strength (GSH, SOD, CAT), and reduce neuroinflammatory activity and apoptosis markers (caspase-3). LT's antioxidant, calcium homeostasis, anti-inflammatory, anti-apoptotic, and neuroprotective properties make it a potential adjuvant to conventional treatment in VCR-induced neuropathy in rats.

(-)-Epigallocatechin-3-gallate decreases the impairment in learning and memory in spontaneous hypertension rats.

Oxidative stress induced by hypertension has been reported to cause alterations in neural cytoarchitecture and cognitive dysfunction. Green tea catechins, especially (-)-epigallocatechin-3-gallate (EGCG), have potent antioxidative properties and protect against various oxidative damages. In this study, we examined the impact of hypertension in rats on locomotor activity, learning, and memory, and EGCG was tested for its potential therapeutic effects in treating hypertension-induced impairment. Blood pressure was measured by the tail-cuff method to confirm high blood pressure in spontaneous hypertension rats (SHRs). Locomotor activity in the open field was increased in SHRs, along with learning and memory impairment in the Morris water maze. Daily EGCG treatment reduced the progressive increase in blood pressure in SHRs, and prevented most of the increased locomotor activity in addition to improving learning and memory. EGCG treatment also decreased the increased level of lipid peroxide production in SHRs and enhanced the antioxidation power in plasma that was observed to be decreased in SHRs. EGCG also decreased the concentration of reactive oxygen species in the hippocampi of SHRs. These indicate a therapeutic effect of EGCG in treating hypertension-induced learning and memory impairment, most probably through its powerful antioxidative properties.

L-Theanine Ameliorated Rotenone-Induced Parkinsonism-like Symptoms in Rats.

Rotenone (RO)-induced neurotoxicity exhibits pathophysiological features similar to those reported in patients with Parkinson's disease (PD), such as nitrosative and oxidative stress, mitochondrial dysfunction, and neural cytoarchitecture alterations in the substantia nigra pars compacta (SNpc)/striatum (ST), which has been used for decades as an animal model of PD in humans. L-Theanine (LT), a major amino acid component of green tea, exhibits potent antioxidant and anti-inflammatory activities and protects against various neural injuries. We investigated the potential therapeutic effects of LT on RO-induced behavioral and neurochemical dysfunction in rats and the neuroprotective mechanisms underlying these effects. Unilateral stereotaxic intranigral infusion of RO into the SNpc to induce PD-like manifestations induced significant behavioral impairment as evaluated using an open field test, rotarod test, grip strength measurement, and beam-crossing task in rats. LT treatment (300 mg/kg i.p., 21 days) ameliorated most RO-induced behavioral impairments. In addition, LT treatment reduced nitric oxide level and lipid peroxidation production, increased mitochondrial function and integrity, as well as the activities of mitochondrial complexes I, II, IV, and V, and reduced the levels of neuroinflammatory and apoptotic markers in the SNpc and ameliorated the levels of catecholamines, GABA and glutamate in the ST induced by RO. These results demonstrate the possible therapeutic effects of LT against RO-induced behavioral impairments, including antioxidative effects, prevention of mitochondrial dysfunction, prevention of neurochemical deficiency, anti-neuroinflammatory effects, and anti-apoptotic effects. This is the first report on the neuroprotective effect of LT against RO-induced behavioral impairments, and the above evidence provides a potential clinically relevant role for LT in the management of human PD.

Naringin Ameliorates Haloperidol-Induced Neurotoxicity and Orofacial Dyskinesia in a Rat Model of Human Tardive Dyskinesia.

Animal models of haloperidol (HAL)-induced neurotoxicity and orofacial dyskinesia (OD) have long been used to study human tardive dyskinesia (TD). Similar to patients with TD, these models show strong pathophysiological characteristics such as striatal oxidative stress and neural cytoarchitecture alteration. Naringin (NAR), a bioflavonoid commonly found in citrus fruits, has potent antioxidative, anti-inflammatory, antiapoptotic, and neuroprotective properties. The present study evaluated the potential protective effects of NAR against HAL-induced OD in rats and the neuroprotective mechanisms underlying these effects. HAL treatment (1 mg/kg i.p. for 21 successive days) induced OD development, characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), which were recorded on the 7th, 14th, and 21st day of drug treatment. NAR (30, 100, and 300 mg/kg) was administered orally 60 min before HAL injection for 21 successive days. On the 21st day, after behavioral testing, the rats were sacrificed, and the nitrosative and oxidative status, antioxidation power, neurotransmitter levels, neuroinflammation, and apoptotic markers in the striatum were measured. HAL induced OD development, with significant increases in the frequency of VCM and TP. NAR treatment (100 and 300 mg/kg) prevented HAL-induced OD significantly. Additionally, NAR treatment reduced the HAL-induced nitric oxide and lipid peroxide production, increased the antioxidation power and neurotransmitter levels in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results first demonstrate the neuroprotective effects of NAR against HAL-induced OD, suggesting that NAR may help in delaying or treating human TD in clinical settings.

Assessment of novel muscarinic acetylcholine receptors in rat cerebral cortex by a tissue segment binding method.

Muscarinic acetylcholine receptors (mAChRs) of rat cerebral cortex were evaluated using a tissue segment radioligand binding assay. [(3)H]-Quinuclidinyl benzilate (QNB, a hydrophobic ligand) specifically bound to mAChRs in the cortex segments. The total mAChRs level was approximately 2,000 fmol/mg protein, which was estimated after incubation for 120 min at 37 degrees C or for 8 h at 4 degrees C. These mAChRs were a mixture of high- and low-affinity sites for N-methylscopolamine (NMS) in a 70:30 ratio. In contrast, only a single high-affinity site for NMS was detected following incubation for 30 min at 37 degrees C, whose abundance was about 70% of that of the total mAChRs. Atropine showed a single affinity for mAChRs under all conditions. These indicate that mAChRs are constitutively expressed not only on plasma membrane sites but also at intracellular sites in rat cerebral cortex and that the receptors at both sites have different affinities for NMS. Acetylcholine completely inhibited [(3)H]-QNB binding to both mAChRs without any change in the subcellular distribution, suggesting the possibility that acetylcholine can access, and bind to, both mAChRs in intact tissue. Two different affinity states for acetylcholine were detected only in plasma membrane mAChRs at 37 degrees C. The present study demonstrates a unique subcellular distribution, and distinct pharmacological profiles, of mAChRs in rat cerebral cortex.

Protective Effect of (-)Epigallocatechin-3-gallate on Rotenone-Induced Parkinsonism-like Symptoms in Rats.

Rotenone (ROT)-induced neurotoxicity has been used for decades as an animal model of Parkinson's disease (PD) in humans. This model exhibits pathophysiological features similar to those reported in patients with PD, namely, striatal nitrosative and oxidative stress, mitochondrial dysfunction, and neural cytoarchitecture alteration. (-)Epigallocatechin-3-gallate (EGCG), the most abundant and potent green tea catechin, has notable anti-oxidative, anti-inflammatory, and neuroprotective effects. The objective of the present study was to investigate the potential protective effects of EGCG on ROT-induced motor and neurochemical dysfunctions in rats. Furthermore, we also aimed to study the neuroprotective mechanisms underlying these effects. ROT treatment (0.5 mg/kg s.c., 21 days) reduced body weight and induced significant motor impairments as assessed using an open-field test, rotarod test, grip strength measurement, and beam-crossing task. EGCG treatment (100 or 300 mg/kg i.p., 60 min prior to ROT administration, 21 days) prevented most of the ROT-induced motor impairments. Moreover, EGCG treatment reduced ROT-induced nitric oxide (NO) level and lipid peroxidation (LPO) production; increased the activity of succinate dehydrogenase (SDH), ATPase, and ETC enzymes and the levels of catecholamines in the striatum; and reduced the levels of neuroinflammatory and apoptotic markers. These results demonstrate the possible neuroprotective effects of EGCG against ROT-induced motor impairments, including anti-oxidatory effect, prevention of mitochondrial dysfunction, prevention of neurochemical deficiency, anti-neuroinflammatory effect, and anti-apoptotic effect. This is the first report about the neuroprotective effect of EGCG against ROT-induced motor impairments, and the above evidence provides a potential clinically relevant role for EGCG in delaying or treating human PD.

Effects of Highly Oxygenated Water in a Hyperuricemia Rat Model.

Recent years have seen a rapidly rising number of oxygenated water brands that claim to impart health benefits and increase athletic performance by improving oxygen availability in the body. Drinks with higher dissolved oxygen concentrations have in recent times gained popularity as potential ergogenic aids, despite the lack of evidence regarding their efficacy. The aim of this study was to characterize oxygenated water and assess the improvement in uric acid metabolism while identifying performance enhancements in animals administered oxygenated water. Oxygenated water was characterized by hydrogen and oxygen nuclear magnetic resonance (NMR) spectroscopy. Hyperuricemia in rats was induced by treatment with oxonic acid potassium salt, and the animals were given oxygenated drinking water before, during, or after oxonic acid treatment. Serum uric acid was measured to confirm the effects on uric acid metabolism. Following oxygenation, the full width at half maximum (FWHM) was reduced to 11.56 Hz and 64.16 Hz in the hydrogen and oxygen NMR spectra, respectively. Oxygenated water molecule clusters were reduced in size due to the reduction in FWHM. Oxygen concentration did not vary significantly with increased temperature. However, standing time played a critical role in the amount of oxygen dissolved in the water. The rat studies indicated that oxygenated water reduced serum uric acid levels and their rate of increase and enhanced uric acid metabolism. A significant improvement in uric acid metabolism and rate of increase in serum uric acid concentration was observed in hyperuricemic rats administered oxygenated water compared to that in rats administered regular water. High oxygen concentrations enhanced the rate of oxygen absorption, leading to increased glycolysis and mitochondrial protein synthesis. Therefore, oxygenated water is a potential adjuvant therapy or health food for treatment of hyperuricemia.

Activation of opioid mu-receptor by sinomenine in cell and mice.

Sinomenine, one of the alkaloids extracted from roots or stems of Sinomenium acutum, is documented to show antinociceptive action but the action mechanism is still unclear. The present study was aimed to investigate the effect of sinomenine on opioid mu-receptor (OMR). In Chinese Hamster Ovary (CHO) cell transfected with OMR, the binding of [(3)H]naloxone was displaced by sinomenine in a concentration-dependent manner. This compound also raised the phosphorylation of OMR in these cells. In a tail-flick test, sinomenine produced dose-dependent antinociception in mice, which was dose-dependently inhibited by pretreatment of naloxonazine, a selective OMR antagonist. Long-term pretreatment with sinomenine may delay the analgesic tolerance of morphine. The obtained results suggest that sinomenine has an ability to activate OMR, implicating the potential of sinomenine to be applied in clinic.

L-Theanine Decreases Orofacial Dyskinesia Induced by Reserpine in Rats.

Reserpine (RES)-induced orofacial dyskinesia (OD) has been used as an animal model for human tardive dyskinesia (TD) for decades, due to its strong pathophysiological association with striatal oxidative stress and neural cytoarchitecture alteration. L-Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative, anti-inflammatory, and neuroprotective effects. In this study, we examined the potential protective effects of LT on RES-induced behavioral and neurochemical dysfunction in rats. RES treatment (1 mg/kg s.c., 3 injections 1 day apart) induced significant increases (p < 0.001) in the frequency of vacuous chewing movements (VCM), tongue protrusion (TP), as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 14 days, starting 10 days before RES injection) was able to prevent most of the RES-induced OD. Moreover, LT treatment reduced the RES-induced lipid peroxidation (LPO) production, increased the antioxidation power and catecholamines in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results indicated that LT was able to counteract the increased oxidative damage, neurotransmitter deficiency, neuroinflammation, and apoptosis induced by RES, and these results have demonstrated the possible neuroprotective effects of LT against RES-induced OD, including antioxidation, neurochemical deficiency prevention, antineuroinflammation, and antiapoptosis. These findings, therefore, suggest a potential role for LT to have a clinically relevant therapeutic effect in delaying or treating human TD.

Effective epidural blood patch volumes for postdural puncture headache in Taiwanese women.

BACKGROUND/PURPOSE: Epidural blood patch (EDBP) is the most commonly used method to treat postdural puncture headache (PDPH). The optimal or effective blood volume for epidural injection is still controversial and under debated. This study compared the therapeutic efficacy of 7.5 mL blood vs. 15 mL blood for EDBP via epidural catheter injection. METHODS: Thirty-three patients who suffered from severe PDPH due to accidental dural puncture during epidural anesthesia for cesarean section or epidural analgesia for labor pain control were randomly allocated into two groups. EDBP was conducted and autologous blood 7.5 mL or 15 mL was injected via an epidural catheter in the semi-sitting position in Group I (n = 17) and II (n = 16), respectively. For all patients in both groups, the severity of PDPH was registered on a 4-point scale (none, mild, moderate, severe) and assessed 1 hour, 24 hours and 3 days after EDBP. RESULTS: There was no significant difference between the two groups of patients at all time points with respect to the severity of PDPH. Two patients in Group I and nine in Group II developed nerve root irritating pain during blood injection (p < 0.05). No systemic complications were noted in both groups of patients throughout EDBP injection. CONCLUSION: We conclude that injection of 7.5 mL autologous blood into the epidural space is comparable to 15 mL blood in its analgesic effect on PDPH, but with less nerve root irritating pain during injection.

Prospective observational pharmacogenetic study of side effects induced by intravenous morphine for postoperative analgesia.

Nausea and vomiting are probably the most unpleasant side effects that occur when morphine used. A number of studies have investigated the effect on pain relief of single nucleotide polymorphisms (SNPs) in genes involved in morphine's metabolism, distribution, binding, and cellular action. The mechanism through which morphine causes nausea and vomiting has not been elucidated clearly. We examined all the reported SNPs which are associated with the complications of morphine, including SNPs in genes for phase I and phase II metabolic enzymes, ABC binding cassette drug transporters, κ and δ opioid receptors, and ion channels implicated in the postreceptor action of morphine.A prospective, observational study in 129 female patients was conducted to investigate the effect of 14 SNPs on nausea or vomiting induced by intravenous patient-controlled analgesia (IVPCA) with morphine after gynecology surgery. Clinical phenotype, subjective complaints, and objective observations were recorded. DNA from blood samples was used to record the SNPs. Eleven SNPs were then analyzed further.No significant association with the presence of phenotype (nausea or vomiting) versus genotype was observed (all P > .05). No significant association with severity of phenotype versus genotype of the 11 SNPs was observed except for unadjusted data for rs2737703.There was no significant difference between severity or incidence of IVPCA morphine-induced nausea and vomiting and genotype (11 SNPs). Further study should perhaps be focused on mRNA and proteinomics rather than SNPs.