The preventive effects of Saccharomyces boulardii against oxidative stress induced by lipopolysaccharide in rat brain.

The brain is sensitive to oxidative stress, which can trigger microglial activation and neuroinflammation. Antioxidant therapies may provide neuroprotection against oxidative stress. In recent years antioxidant effects of probiotics and their possible mechanisms in oxidative stress-related models have been determined. In the current study, for the first time, we assessed the effects of Saccharomyces boulardii on oxidative stress provoked by lipopolysaccharide (LPS) in the rat brain. Four groups of animals were used, including the control, LPS, S. boulardii + LPS, and S. boulardii groups. All animals received either saline or S. boulardii (1010 CFU) by gavage for four weeks. Between days 14 and 22, all animals received either LPS (250 µg/kg) or saline by intraperitoneal (i.p.) injection. S. boulardii was able to inhibit lipid peroxidation and prevent the reduction of antioxidant levels, including glutathione and catalase in the model of oxidative stress induced by LPS in the rat hippocampus and cortex. Also, it increased the lowered ratio of glutathione/oxidized glutathione in both tissues. Serum levels of anti-inflammatory interleukin 10 (IL-10) and proinflammatory cytokines IL-6 and IL-8 increased and decreased, respectively. S. boulardii has potential antioxidant activities in oxidative stress-related model, possibly modulating gut microbiota, immune defense, and antioxidant enzyme activities that can be considered in preventing oxidative stress-related central nervous system (CNS) diseases.

The elderberry diet protection against intrahippocampal Aß-induced memory dysfunction; the abrogated apoptosis and neuroinflammation.

This study evaluates whether elderberry (EB) effectively decreases the inflammation and oxidative stress in the brain cells to reduce Aß toxicity. In the Aß + EB group, EB powder was added to rats' routine diet for eight consecutive weeks. Then, spatial memory, working memory, and long-term memory, were measured using the Morris water maze, T-maze, and passive avoidance test. Also, in this investigation immunohistopathology, distribution of hippocampal cells, and gene expression was carried out. Voronoi tessellation method was used to estimate the spatial distribution of the cells in the hippocampus. In addition to improving the memory functions of rats with Aß toxicity, a reduction in astrogliosis and astrocytes process length and the number of branches and intersections distal to the soma was observed in their hippocampus compared to the control group. Further analysis indicated that the EB diet decreased the caspase-3 expression in the hippocampus of rats with Aß toxicity. Also, EB protected hippocampal pyramidal neurons against Aß toxicity and improved the spatial distribution of the hippocampal neurons. Moreover, EB decreased the expression of inflammatory and apoptotic genes. Overall, our study suggest that EB can be considered a potent modifier of astrocytes' reactivation and inflammatory responses.

Curcumin attenuates morphine dependence by modulating µ-opioid receptors and glial cell-activated neuroinflammation in rat.

In recent years, the association between neuroinflammation and opioid dependence has attracted considerable attention. Curcumin, a component of the Curcuma longa, has been shown to act as a suppressor of glial cells and inflammatory cytokines. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on neuroinflammation and µ-opioid receptors in the rat prefrontal cortex. To induce morphine dependence in male Wistar rats, morphine was administered i.p. once daily for 18 days in an escalating dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Immunofluorescence staining and ELISA methods were used to evaluate glial cells activity and inflammatory cytokines levels, respectively. Western blotting was used to evaluate the expression of µ-opioid receptors. The administration of curcumin (2.5, 5, and 10 mg/kg) for 9 days significantly attenuated the symptoms of morphine withdrawal syndrome. The prefrontal cortex concentration of TNF-α and IL-6 was also reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Furthermore, curcumin decreased the number of Iba1 and GFAP positive cells in morphine-dependent rats. Moreover, the expression of µ-opioid receptors was significantly reduced by curcumin (10 mg/kg). The results of this study demonstrate that curcumin attenuates morphine dependence in rats through an inhibitory effect on neuroinflammation and a decrease in the expression of µ-opioid receptors in the prefrontal cortex.

Minocycline Improves Memory by Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in a Rat Model of Cerebral Ischemia-Reperfusion.

Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia, ultimately resulting in memory dysfunction. Hence, the applying antioxidant agents could be beneficial in managing memory deficits after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess the minocycline effect on the impairment of synaptic plasticity and memory after cerebral ischemia-reperfusion in rats. Methods: Transient occlusion of common carotid arteries was used to induce ischemiareperfusion injury in rats. Single or multiple (once daily for 7 days) dose(s) of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, long-term hippocampal potentiation, and the activity of antioxidant enzymes were assessed. Results: The passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reducing the duration of staying in a dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats treated (but not pretreated) with minocycline (40 mg/kg) showed a significant increase in the amplitude of the field excitatory postsynaptic potentials in the dentate gyrus area of the hippocampus. The treatment (but not pretreatment) with minocycline (20 and 40 mg/kg) resulted in a significant increase in the activity of catalase, glutathione peroxidase, and superoxide dismutase in the hippocampus. Conclusion: It was determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats by improving hippocampal synaptic plasticity and restoring antioxidant enzyme activity. Highlights: Minocycline enhances passive avoidance memory after cerebral ischemia-reperfusion.Minocycline increases enzymatic antioxidant capacity in hippocampal formation.Minocycline improves synaptic plasticity in perforant path-granule cell synapse. Plain Language Summary: Stroke is a common neurological disease with a relatively high mortality rate and disabilities worldwide. More than half of the patients who have had an episode of stroke suffer from the impairment of sensorimotor function and language problems as well as learning and memory disorders. Oxidative stress plays an important role in memory impairment following brain ischemia. Hence, the application of antioxidant agents could be beneficial in managing memory deficits after stroke. Minocycline is a tetracycline antibiotic that is used for the treatment of infectious diseases; it can also function as a potent antioxidant medication. Hence, we hypothesized that minocycline could attenuate memory impairment after brain ischemia. We examined this hypothesis in a rat model of brain ischemia. In this model, the main arteries that supply the brain with oxygenated blood were occluded to induce brain ischemia in the rats. Then, minocycline was administered to the rats, which were subjected to brain ischemia. Seven days later, memory function in the rats was evaluated. The results showed that minocycline could enhance the activity of antioxidant enzymes in the brain, which physiologically fight off oxidative stress. This property of minocycline protects brain cells against ischemic injury and thereby increases the transmission of neuronal signals from one cell to another cell in the memory centers in the brain. These effects ultimately increase the memory function of rats, which was evident in the behavioral memory test. Overall, the study results suggest that minocycline can be considered a memory enhancer drug in patients who suffer from learning and memory disorders following a stroke.

Drug Delivery Using Hydrophilic Metal-Organic Frameworks (MOFs): Effect of Structure Properties of MOFs on Biological Behavior of Carriers.

To study the influence of pore structural properties of metal-organic frameworks (MOFs) on drug adsorption and delivery, we synthesized two MOF termed TMU-6(RL1) {[Zn(oba)(RL1)0.5]n·(DMF)1.5} and TMU-21(RL2) {[Zn(oba)(RL2)0.5]n·(DMF)1.5} with amine basic N-donor pillars containing phenyl or naphthyl cores with various hydrophilic properties around the main center of the reaction. TG, IR, XPS, and PXRD analyses were used to extensively characterize the MOFs. The synthesized carriers showed high adsorption efficiency, stability, and controlled release. As an anticancer drug, Nimesulide (Nim) was adsorbed to MOFs using multiple adsorption mechanisms, such as Hostπ-πGuest interaction and HostN-H···OGuest hydrogen bonds. Moreover, Hirshfeld surface analysis showed when the benzene core was replaced with the naphthalene core, the percentage of intermolecular interactions of π···π and N···H by amine sites in TMU-21(RL2) decreased compared with TMU-6(RL1), while the percentage of these interactions with guest molecules increased. The results showed that changes in the hydrophobicity/hydrophilicity properties of MOFs would alter their ability to adsorb Nim in the pore of the frameworks. In vitro anticancer studies also showed that the cytotoxicity of Nim in MOFs@Nim composites against human cervical cancer cell line (HeLa cells) and human colon cancer cell line (HT-29 cells) is much higher than that of free Nim. Generally, based on the results, it can be said that the biological behavior of carriers can be regulated by adjusting the structure properties of MOFs.

The Synergistic Anti-Apoptosis Effects of Amniotic Epithelial Stem Cell Conditioned Medium and Ponesimod on the Oligodendrocyte Cells.

Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and eventually neurons. So, we need new approaches for axonal protection and remyelination. Amniotic epithelial stem cells amniotic epithelial cells, as a neuroprotective and neurogenic agent, are a proper source in tissue engineering and regenerative medicine. Due to differentiation capability and secretion of growth factors, AECs can be a candidate for the treatment of MS. Moreover, sphingosine-1-phosphate (S1P) receptor modulators were recently approved by FDA for MS. Ponesimod is an S1P receptor-1 modulator that acts selectively as an anti-inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. In this study, due to the characteristics of AECs, they are considered a treatment option in MS. The conditioned medium of AECs concurrently with ponesimod was used to evaluate the viability of the oligodendrocyte cell line after induction of cell death by cuprizone. Cell viability after treatment by conditioned medium and ponesimod was increased compared to untreated groups. Also, the results showed that combination therapy with CM and ponesimod had a synergistic anti-apoptotic effect on oligodendrocyte cells. The combination treatment with CM and ponesimod reduced the expression of caspase-3, caspase-8, Bax, and Annexin V proteins and increased the relative BCL-2/Bax ratio, indicating inhibition of apoptosis as a possible mechanism of action. Based on these promising results, combination therapy with amniotic stem cells and ponesimode could be a proper alternative for multiple sclerosis treatment.

Analgesic effects of cuminic alcohol (4-isopropylbenzyl alcohol), a monocyclic terpenoid, in animal models of nociceptive and neuropathic pain: Role of opioid receptors, L-arginine/NO/cGMP pathway, and inflammatory cytokines.

Cuminic alcohol (4-isopropylbenzyl alcohol; 4-IPBA) is a monocyclic terpenoid found in the analgesic medicinal plants Cuminum cyminum and Bunium persicum. The current study assessed the analgesic effects of 4-IPBA in different animal models of pain. Hot plate, formalin, and acetic acid tests were used to evaluate nociceptive pain in mice. The involvement of opioid receptors and the L-arginine/NO/cGMP/K+ channel pathway in 4-IPBA effects were investigated. Allodynia and hyperalgesia were assessed following peripheral neuropathy induced by chronic constriction of the sciatic nerve in rats. The spinal levels of inflammatory cytokines were measured using the ELISA method. The drugs and compounds were administered intraperitoneally. The results showed that 4-IPBA (200 and 400 mg/kg) significantly prolonged the hot plate latency. This effect was antagonized by naloxone (2 mg/kg). 4-IPBA (25-100 mg/kg) also significantly attenuated formalin- and acetic acid-induced nociceptive pain. L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg) reversed while L-NAME (30 mg/kg) and methylene blue (20 mg/kg) potentiated the antinociceptive effects of 4-IPBA in the writhing test. Glibenclamide (10 mg/kg) and tetraethylammonium chloride (4 mg/kg) did not have any influence on the 4-IPBA effect. Furthermore, 4-IPBA (6.25-25 mg/kg) significantly relieved mechanical allodynia, cold allodynia, and hyperalgesia in rats. The concentrations of TNF-α and IL-1ß in the spinal cord of rats were decreased by 4-IPBA. No evidence of 4-IPBA-induced toxicity was found in behavioral or histopathological examinations. These results demonstrate that 4-IPBA attenuates nociceptive and neuropathic pain through the involvement of opioid receptors, the L-arginine/NO/cGMP pathway, and anti-inflammatory functions.

Attenuating effect of paroxetine on memory impairment following cerebral ischemia-reperfusion injury in rat: The involvement of BDNF and antioxidant capacity.

Memory impairments are frequently reported in patients suffering from brain ischemic diseases. Oxidative/nitrosative stress, synaptic plasticity, and brain-derived neurotrophic factor (BDNF) are involved in the physiopathology of brain ischemia-induced memory disorders. In the present study, the effect of paroxetine as an efficacious antidepressant medication with antioxidant properties was evaluated on passive avoidance memory deficit following cerebral ischemia in rats. Transient occlusion of common carotid arteries was applied to induce ischemia-reperfusion injury in male Wistar rats. Paroxetine (5, 10, 20 mg/kg) was administered intraperitoneally once daily before (for 3 days) or after (for 7 days) the induction of ischemia. A week after ischemia-reperfusion injury, passive avoidance memory, long-term potentiation (LTP), BDNF levels, total antioxidant capacity, the activity of antioxidant enzymes (including catalase, glutathione peroxidase, and superoxide dismutase), the concentration of malondialdehyde (MDA), and nitric oxide (NO) were investigated in the hippocampus. In the passive avoidance test, paroxetine significantly increased the step-through latency and decreased the time spent in the dark compartment. This affirmative function of paroxetine on the passive avoidance memory was accompanied by the improvement of hippocampal LTP and an obvious augmentation in the BDNF contents. Besides, paroxetine caused a significant rise in the total antioxidant capacity and antioxidant enzyme activity; while decreased the hippocampal levels of NO and MDA. It was ultimately attained that paroxetine attenuates cerebral ischemia-induced passive avoidance memory dysfunction in rats by the enhancement of hippocampal synaptic plasticity and BDNF content together with the suppression of oxidative/nitrosative stress.

Antinociceptive and antineuropathic effects of cuminaldehyde, the major constituent of Cuminum cyminum seeds: Possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian traditional medicine, Cuminum cyminum is a unique medicinal herb for pain relief. Cuminaldehyde has been distinguished as the major constituent of C. cyminum seeds; even though, the analgesic effect of cuminaldehyde has not yet been examined. AIM OF THE STUDY: The nobility of this study was to assess cuminaldehyde effect on nociceptive and neuropathic pains; furthermore, evaluation of its possible mechanisms of action. MATERIALS AND METHODS: Hot plate, formalin, and acetic acid-induced writhing tests were used to evaluate nociception in mice. Naloxone (opioid receptors antagonist), L-arginine (nitric oxide (NO) precursor), L-NAME (NO synthase inhibitor), sodium nitroprusside (NO donor), methylene blue (guanylyl cyclase inhibitor), sildenafil (phosphodiesterase inhibitor), and glibenclamide (KATP channel blocker) were used to determine the implication of opioid receptors and L-arginine/NO/cGMP/KATP channel pathway. Allodynia and hyperalgesia were investigated in the CCI (chronic constriction injury) model of neuropathic pain in rats. The ELISA method was used to measure the inflammatory cytokines in serum samples of rats. The entire chemicals were intraperitoneally injected. RESULTS: Cuminaldehyde (100 and 200 mg/kg) significantly decreased the latency to nociceptive response in the hot plate test. The outcome of cuminaldehyde was completely antagonized by naloxone (2 mg/kg). Formalin- and acetic acid-induced nociception was significantly inhibited by cuminaldehyde (12.5-50 mg/kg). The antinociceptive effect of cuminaldehyde was reversed in writhing test by L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg); however, L-NAME (30 mg/kg) and methylene blue (20 mg/kg) enhanced the effect of cuminaldehyde. Glibenclamide (10 mg/kg) did not alter the antinociceptive effects of cuminaldehyde. In the CCI-induced neuropathy, cuminaldehyde (25-100 mg/kg) significantly alleviated allodynia and hyperalgesia and decreased the serum levels of TNF-α and IL-1ß. CONCLUSION: It was attained magnificently that cuminaldehyde exerts antinociceptive and antineuropathic effects through the involvement of opioid receptors, L-arginine/NO/cGMP pathway, and anti-inflammatory function.

The Attenuating Effect of Curcumin on Morphine Dependence in Rats: The Involvement of Spinal Microglial Cells and Inflammatory Cytokines.

New evidence suggests an important role for spinal glial cells in the development of opioid dependence. Curcumin, a component of the Curcuma Longa, has shown to act as a suppressor of microglial cells. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on spinal microglial cells and inflammatory cytokines. In order to induce morphine dependence in male Wistar rats, morphine was administered intraperitoneally (i.p.) once daily for 9 days in an increasing dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Naloxone-precipitated abstinence syndrome was used to assess the behavioral symptoms of morphine dependence. Immunofluorescence staining of Iba1 and ELISA test were used to measure spinal microglial activity and inflammatory cytokines levels, respectively. The results showed that curcumin (2.5, 5, and 10 mg/kg) significantly decreased jumping, leaning, and diarrhea in morphine-dependent rats. In addition, the spinal concentration of TNF-α and IL-6 was reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Moreover, curcumin showed a potent attenuating effect on the number of Iba1 positive cells in rats which were subjected to morphine dependence. The results of this study demonstrated that curcumin exerts a remarkable reducing effect on morphine dependence in rats. The findings showed that the therapeutic effect of curcumin on morphine dependence is mediated through the suppression of activated microglial cells and reduction of inflammatory cytokines levels in the spinal cord.

Analgesic effect of α-terpineol on neuropathic pain induced by chronic constriction injury in rat sciatic nerve: Involvement of spinal microglial cells and inflammatory cytokines.

OBJECTIVES: Neuropathic pain is a prevalent and debilitating neurological disorder. Ample evidence indicates that microglial cells and inflammatory cytokines are involved in the pathogenesis of neuropathic pain. Alpha-terpineol is a monoterpenoid alcohol with inhibitory effect on inflammatory cytokines. The main purpose of this study was to evaluate the effect of α-terpineol on neuropathic pain in rats. MATERIALS AND METHODS: Chronic constriction injury (CCI) model was utilized to induce neuropathic pain in male Wistar rats. The rats were randomly divided into control, sham, α-terpineol, and gabapentin groups. Normal saline, α-terpineol (25, 50, and 100 mg/kg), and gabapentin (100 mg/kg) were administered intraperitoneally in the above-mentioned groups once daily for 14 days post-CCI. Behavioral tests, including Von Frey, acetone, and Hargreaves were used to assess mechanical allodynia, cold allodynia, and hyperalgesia in rats. Iba1 immunostaining and ELISA procedures were used to assess the activation of microglial cells and inflammatory cytokines level. RESULTS: The results showed that α-terpineol (50 and 100 mg/kg) significantly attenuated mechanical allodynia, cold allodynia, and hyperalgesia in the neuropathic rats. The analgesic effect of α-terpineol (100 mg/kg) was comparable with that of gabapentin as a standard antineuropathic pain drug. In addition, α-terpineol (25, 50 and 100 mg/kg) significantly decreased the number of Iba1-positive cells and diminished the concentration of IL-1ß and TNF-α in the spinal tissue. CONCLUSION: It was ultimately attained that α-terpineol attenuates neuropathic pain through the suppression of the microglial cells and reduction of inflammatory cytokine levels in the spinal cord of rats.

Role of L-arginine/NO/cGMP/KATP channel signaling pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.

OBJECTIVES: Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats. MATERIALS AND METHODS: Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone. RESULTS: Local ipsilateral (20 and 40 µg, IPL) but not contralateral and ICV (4 and 8 µg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 µg, IPL or ICV) and SNAP (200 µg, IPL or ICV) increased while l-NAME (100 µg, IPL or 1 µg, ICV) and methylene blue (400 µg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 µg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test. CONCLUSION: The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.

Role of l-arginine/SNAP/NO/cGMP/KATP channel signalling pathway in antinociceptive effect of α-terpineol in mice.

OBJECTIVES: The main purpose of this study was to assess the role of l-arginine/SNAP/NO/cGMP/KATP channel pathway in analgesic effects of α-terpineol in mice. METHODS: Male NMRI mice were pretreated intraperitoneally with NO precursor (l-arginine, 100 mg/kg), NO synthase inhibitor (l-NAME, 30 mg/kg), NO donor (SNAP, 1 mg/kg), guanylyl cyclase inhibitor (methylene blue, 20 mg/kg), PDE inhibitor (sildenafil, 0.5 mg/kg), KATP channel blocker (glibenclamide, 10 mg/kg) and naloxone (2 mg/kg) 20 min before the administration of α-terpineol. The formalin test was performed 20 min after the administration of α-terpineol, and nociceptive responses of mice were recorded during 30 min. KEY FINDINGS: A significant and dose-dependent antinociception was produced by α-terpineol (40 and 80 mg/kg) in both the phases of formalin test. The antinociceptive effect of α-terpineol was significantly potentiated by l-arginine in the second phase while significantly antagonized by l-NAME in both phases of formalin test. Also, SNAP and sildenafil non-significantly enhanced-while methylene blue significantly diminished-the antinociceptive effect of α-terpineol in both phases of formalin test. Glibenclamide significantly reversed the α-terpineol-induced antinociception, indicating the involvement of KATP channels in antinociceptive effect of α-terpineol. CONCLUSIONS: These results indicate that the antinociceptive effect of α-terpineol is mediated through l-arginine/SNAP/NO/cGMP/KATP channel pathway.

Interference-free Determination of Carbamazepine in Human Serum Using High Performance Liquid Chromatography: A Comprehensive Research with Three-way Calibration Methods.

In the present study, a comprehensive and systematic strategy was described to evaluate the performance of several three-way calibration methods on a bio-analytical problem. Parallel factor analysis (PARAFAC), alternating trilinear decomposition (ATLD), self-weighted alternating trilinear decomposition (SWATLD), alternating penalty trilinear decomposition (APTLD), and unfolded partial least squares combined with the residual bilinearization procedure (U-PLS/RBL) were applied on high performance liquid chromatography with photodiode-array detection (HPLC-DAD) data to quantify carbamazepine (CBZ) in different serum samples. Using the proposed approach, successfully quantification of CBZ in human plasma, even in the presence of diverse uncalibrated serious interfering components was achieved. Moreover, the accuracy and precision of each algorithm for analyzing CBZ in serum samples were compared using root mean square error of prediction (RMSEP), the recovery values and figures of merits and reproducibility of the analysis. Satisfying recovery values for the analyte of interest were obtained by HPLC-DAD on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH = 7.5) buffer solution (45:55) coupled with second-order calibrations. Decreas of the analysis time and less solvent consumption are some of the pluses of this method. The analysis of real samples showed that the modeling of complex chromatographic profiles containing CBZ as the target drug using any of the mentioned algorithms can be potentially benefit drug monitoring in therapeutic research.

Protective effect of α-terpineol against impairment of hippocampal synaptic plasticity and spatial memory following transient cerebral ischemia in rats.

OBJECTIVES: Cerebral ischemia is often associated with cognitive impairment. Oxidative stress has a crucial role in the memory deficit following ischemia/reperfusion injury. α-Terpineol is a monoterpenoid with anti-inflammatory and antioxidant effects. This study was carried out to investigate the effect of α-terpineol against memory impairment following cerebral ischemia in rats. MATERIALS AND METHODS: Cerebral ischemia was induced by transient bilateral common carotid artery occlusion in male Wistar rats. The rats were allocated to sham, ischemia, and α-terpineol-treated groups. α-Terpineol was given at doses of 50, 100, and 200 mg/kg, IP once daily for 7 days post ischemia. Morris water maze (MWM) test was used to assess spatial memory and in vivo extracellular recording of long-term potentiation (LTP) in the hippocampal dentate gyrus was carried out to evaluate synaptic plasticity. Malondialdehyde (MDA) was measured to assess the extent of lipid peroxidation in the hippocampus. RESULTS: In MWM test, α-terpineol (100 mg/kg, IP) significantly decreased the escape latency during training trials (P<0.01). In addition, α-terpineol increased the number of crossings over the platform location and decreased average proximity to the target in probe trial (P<0.05). In electrophysiological recording, α-terpineol (100 mg/kg) facilitated the induction of LTP in the hippocampus which was persistent over 2 hr. α-Terpineol (100 and 200 mg/kg) also significantly lowered hippocampal MDA levels in rats subjected to cerebral ischemia. CONCLUSION: These findings indicate that α-terpineol improves cerebral ischemia-related memory impairment in rats through the facilitation of LTP and suppression of lipid peroxidation in the hippocampus.

Chemometrics enhanced HPLC-DAD performance for rapid quantification of carbamazepine and phenobarbital in human serum samples.

This paper describes development and validation of a simple and efficient bioanalytical procedure for simultaneous determination of phenobarbital and carbamazepine in human serum samples using high performance liquid chromatography with photodiode-array detection (HPLC-DAD) regarding a fast elution methodology in less than 5 min. Briefly, this method consisted of a simple deproteinization step of serum samples followed by HPLC analysis on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH=7.5) buffer solution (45:55). Due to the presence of serum endogenous components as non-calibrated components in the sample, second-order calibration based on multivariate curve resolution-alternating least squares (MCR-ALS), has been applied on a set of absorbance matrices collected as a function of retention time and wavelengths. Acceptable resolution and quantification results were achieved in the presence of matrix interferences and the second-order advantage was fully exploited. The average recoveries for carbamazepine and phenobarbital were 89.7% and 86.1% and relative standard deviation values were lower than 9%. Additionally, computed elliptical joint confidence region (EJCR) confirmed the accuracy of the proposed method and indicated the absence of both constant and proportional errors in the predicted concentrations. The developed method enabled the determination of the analytes in different serum samples in the presence of overlapped profiles, while keeping experimental time and extraction steps at minimum. Finally, the serum concentration levels of carbamazepine in three time intervals were reported for morphine-dependents who had received carbamazepine for treating their neuropathic pain.