Heavy metals in hair and nails as markers of occupational hazard among welders working in United Arab Emirates.

Studies have shown that hair and nail samples can be used as a marker to assess occupational exposure to heavy metals. The objective of this study was to estimate the levels of heavy metals: Lead (Pb), Nickel (Ni), Cadmium (Cd), and Manganese (Mn) in hair and nail samples of welders working in United Arab Emirates and to find an association between the heavy metal concentration with the parameters like smoking habits, exposure/day, years of experience and use of protective personal equipment (PPE). Hair and toes nail samples were collected from exposed and non-exposed subjects with respect to, social habits, exposure/day and years of welding experience. The levels of Pb, Cd, Mn, and Ni, in hair and toenails, assayed by atomic absorption spectrophotometer. We observed that the metal concentration was higher in toenail as compared to hair samples in both the groups. Cd was significantly high in both the groups whereas, Mn in the hair was high in the exposed group. The Mn in hair was notably higher among smokers and the Cd in hair and Ni in the nail samples was significantly higher in the subjects with > 8 h/day exposure. The concentration of Cd and Ni in hair increased with increasing years of experience and was maximum in the subjects with welding experience of > 20 years. Our results signify that hair and nail samples can be used as an indicator to heavy metal exposure. Given that the present study shows high level of some metals in the hair and nail of welders, awareness of occupational hazards and annual assessment of welder's health is necessary.

Bidirectional Relationship between COVID-19 and Diabetes: Role of Renin-Angiotensin-Aldosterone System and Drugs Modulating It.

Numerous reports have suggested that diabetic patients are at high risk for the development of severe symptoms of coronavirus disease-2019 (COVID-19). However, a few studies have recently proposed that the relationship between diabetes and COVID-19 is bidirectional, as severe acute respiratory syndrome-coronavirus-2 also has the capability to induce diabetes. Various mechanisms have been identified and proposed to be involved in this binary association. In this review, the importance and impact of renin-angiotensin-aldosterone system (RAAS) in this two-way association of COVID-19 and diabetes has been summarized. The role and effect of drugs modulating RAAS directly or indirectly has also been discussed, as they can majorly impact the course of treatment in such patients. Further reports and data can present a clear picture of RAAS and its modulators in restoring the balance of dysregulated RAAS in COVID-19.

Analysis of phthalate esters in two different baby care products available in United Arab Emirates.

Phthalates are used as plasticizers in a wide range of products and are known to affect the human health adversely. Hence, the present study was carried out to identify and quantify the presence of four phthalates namely dimethyl phthalate (DMP), dibutyl phthalate (DBP), and diethyl phthalate (DEP), di (2-ethylhexyl) phthalate (DEHP) in the two baby products i.e. baby oils and baby lotions. The daily exposure levels and hazard index of each phthalate were also calculated. It was an analytical study where two different brands of samples of baby oil and baby lotion each, from the date of manufacturing of 3, 10, and 20 months were collected. The extraction of phthalates from different samples was done and analyzed using HPTLC. Results showed the presence of all four phthalates, although some phthalates were not present in 3 M samples. The maximum concentration of all the phthalates was found in 20 M samples. Their concentration increased with the storage time indicating the possibility of leaching and migration of phthalates from the container into the product. The hazard indices for phthalates estimated for baby oil and baby lotion were found below 1, which denotes that the daily phthalate exposures are within the regulatory limits. It is important to consider that the exposure to phthalates can occur not only by dermal contact of these baby products but also through other routes. Hence, the study signifies the importance of phthalates concentration in such regularly used products.

Activation of indoleamine 2, 3- dioxygenase pathway by olanzapine augments antidepressant effects of venlafaxine in mice.

Recent clinical studies report antipsychotics as a better option to augment the action of antidepressants in treatment resistant cases. However, the proper mechanisms underlying the antidepressant effect of antipsychotics is still not clear. Indolamine 2, 3 dioxygenase (IDO) pathway is considered to be an important pathway in pro-inflammatory cytokine associated stress-induced depression. The present study investigated the antidepressant effect of venlafaxine, olanzapine and their combinations in chronic forced-swim stress-induced depression in mice. In addition, the role of pro-inflammatory cytokines and IDO-mediated pathway was investigated. Swiss albino mice were subjected to chronic forced-swim stress and evaluation for antidepressant-like activity was performed on 7th, 14th and 21st day following which serum levels of pro-inflammatory cytokines (IL-1ß and IL-6 levels) and the levels of hippocampal kynurenine (KYN), tryptophan (TRP) and serotonin (5HT) were estimated. The combination exhibited augmentation of antidepressant-like activity of venlafaxine by olanzapine in chronic forced-swim stress model. Further, it reversed the enhanced serum IL-1ß and IL-6 and reverted the increased activity of IDO as measured by ratio of hippocampal KYN/TRP and 5HT/TRP in stressed mice. Augmentation of antidepressant effect of venlafaxine by olanzapine is thus mediated by normalising the shift from KYN to TRP pathway in chronic forced swim induced stressed mice.

Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus.

The present study was designed to investigate the neuroprotective effect of naringin (NR) alone as well as its combination with sertraline (SRT) against doxorubicin (DOX)-induced neurobehavioral and neurochemical anomalies. DOX (15 mg/kg; i.p.) administration caused behavioral alterations, oxidative stress, neuroinflammation, mitochondrial dysfunction and monoamines alteration in male Wistar rats. NR (50 and 100 mg/kg; i.p.) and SRT (5 mg/kg; i.p.) treatment significantly attenuated DOX-induced anxiety and depressive-like behavior as evident from elevated plus maze (EPM) and modified forced swimming test (mFST), respectively. NR treatment significantly attenuated DOX-induced raised plasma corticosterone (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels in the hippocampus (HC). Furthermore, we found that combination of NR and SRT regimen ameliorated DOX-induced behavioral anomalies through modulation of the 5-HT level and mitochondrial complexes protection pathway along with alleviation of oxidative stress in the HC region. Therefore, NR treatment alone or in combination with SRT could be beneficial against DOX-induced neurotoxicity.

Augmentation of effect of venlafaxine by folic acid in behavioral paradigms of depression in mice: Evidence of serotonergic and pro-inflammatory cytokine pathways.

BACKGROUND: Though venlafaxine is an antidepressant with similar efficacy as selective serotonin receptor inhibitors, dose dependent adverse effects limit its use. Depression is associated with increased levels of pro-inflammatory cytokines. METHODS: The study investigated the effect of combining low/serotonergic dose of venlafaxine with folic acid in mice exposed to chronic forced swim stress for 21 days during which immobility and swimming time following forced swim test (FST) and immobility time in tail suspension test (TST) were measured every 7th, 14th and 21st day. The serum level of pro-inflammatory cytokines (IL-1ß and IL-6) and whole brain levels of monoamines (serotonin, norepinephrine and dopamine) were estimated. RESULTS: An augmentation of antidepressant effect was observed in both forced swim test and tail suspension test following combination of venlafaxine (2 and 4mg/kg) with folic acid (5 and 10mg/kg) after 14 and 21 days of treatment. On brain serotonin level also, a significant augmentation was observed when venlafaxine (4mg/kg) was combined with folic acid (10mg/kg). Further, the combination significantly reversed the elevated levels of serum pro-inflammatory cytokines, IL-1ß and IL-6 observed in chronic FST-induced stressed mice. CONCLUSIONS: Combining low dose venlafaxine with an augmenting agent like folic acid, thus, appears to be an optimum strategy to increase its therapeutic efficacy and to reduce its dose.

Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats.

CONTEXT: Doxorubicin (Dox) is one of the most active chemotherapeutic agents used to treat various types of cancers. Its clinical utility is compromised due to fatal cardiac toxicity characterized by an irreversible cardiomyopathy. OBJECTIVE: This study evaluates the cardioprotective potential of naringin (NR) against Dox-induced acute cardiac toxicity in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into five groups. NR (50 and 100 mg/kg) was administered intraperitoneally (i.p.) daily from 0 to 14 d. Doxorubicin (15 mg/kg, i.p.) was given as a single dose on the 10th day. On the 14th day, all animals were sacrificed and oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) activities, and all mitochondrial complexes (I-IV) activities were evaluated along with histopathological studies of the heart. RESULTS: Doxorubicin-induced cardiotoxicity was confirmed by increased (p < 0.05) MDA, decreased (p < 0.05) GSH levels, SOD, and CAT activities, mitochondrial complexes (I-IV) activities in the heart tissue. NR (100 mg/kg) showed cardioprotection as evident from significant decreased MDA (p < 0.001) level, raised (p < 0.001) GSH level, SOD and CAT activities and increased mitochondrial complexes I (p < 0.01), II (p < 0.001), III (p < 0.001), and IV (p < 0.05) activities. Further, Dox-induced cardiotoxicity was confirmed by histopathological studies. These obtained results indicated the protective role of NR against Dox-induced cardiac toxicity in rats. CONCLUSION: NR can be used in combination with Dox due to its high cardioprotective effect against Dox-induced cardiomyopathy.

A comparative study on the cardioprotective potential of atorvastatin and simvastatin in hyperhomocysteinemic rat hearts.

The present study has been deliberated in order to compare the cardioprotective potential of 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, Atorvastatin and Simvastatin in hyperhomocysteinemic rat hearts. L-methionine (1.7 g/kg/day orally) was administered to rats for 4 weeks to produce experimental hyperhomocysteinemia (Hhcy). Isolated Langendorff-perfused normal and hyperhomocysteinemic rat hearts were subjected to global ischemia for 30 min followed by reperfusion for 120 min. The extent of myocardial damage was assessed in terms of myocardial infarct size using triphenyltetrazolium chloride (TTC) staining, and release of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent; whereas the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation and reduced glutathione. Ischemia-reperfusion (I/R) was noted to produce myocardial injury in normal and hyperhomocysteinemic rat hearts, assessed in terms of increase in myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Treatment with Atorvatstain (50 µM) and Simvastatin (10 µM) afforded cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts as assessed in terms of reductions in myocardial infarct size, LDH and CK levels in coronary effluent and oxidative stress. It may be concluded that reductions in the high degree of oxidative stress may be responsible for the observed cardioprotective potential of Atorva-and Simvastatin, and both statins can be used interchangeably to afford cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts.

A validated HPLC-UV method and optimization of sample preparation technique for norepinephrine and serotonin in mouse brain.

CONTEXT: Norepinephrine and serotonin are two important neurotransmitters whose variations in brain are reported to be associated with many common neuropsychiatric disorders. Yet, relevant literature on estimation of monoamines in biological samples using HPLC-UV is limited. OBJECTIVE: The present study involves the development of a simultaneous HPLC-UV method for estimation of norepinephrine and serotonin along with optimization of the sample preparation technique. MATERIALS AND METHODS: Chromatographic separation was achieved by injecting 20 µL of the sample after extraction into Quaternary pump HPLC equipped with C18 column using 0.05% formic acid and acetonitrile (90:10, v/v) as the mobile phase with 1 mL min(-1) flow rate. The developed method was validated as per the ICH guidelines in terms of linearity, accuracy, repeatability, precision, and robustness. RESULTS AND DISCUSSION: The method showed a wide range of linearity (50-4000 and 31.25-4000 ng mL(-1) for norepinephrine and serotonin, respectively). The recovery was found to be in the range of 86.04-89.01% and 86.43-89.61% for norepinephrine and serotonin, respectively. The results showed low value of %RSD for repeatability, intra and inter-day precision, and robustness studies. Four different methods were used for the extraction of these neurotransmitters and the best one with maximum recovery was ascertained. CONCLUSION: Here, we developed and validated a simple, accurate, and reliable method for the estimation of norepinephrine and serotonin in mice brain samples using HPLC-UV. The method was successfully applied to quantify these neurotransmitters in mice brain extracted by optimized sample preparation technique.

Activation of AKT/GSK3ß pathway by TDZD-8 attenuates kainic acid induced neurodegeneration but not seizures in mice.

Activation of glycogen synthase kinase3ß (GSK3ß), an enzyme that regulates a multitude of cellular signaling pathways, is implicated in neurodegenerative processes observed in an array of CNS diseases. We examined the hypothesis that the pathological changes in an acute kainic acid (KA) induced excitotoxicity model, relevant to human temporal lobe epilepsy (TLE), could be sensitive to inhibition of GSK3ß by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) treatment in Swiss albino mice. Immediate seizure responses due to KA were recorded. Neurodegenerative and morphogenic changes were examined by western blot analysis and light microscopy, respectively, 48 h after KA administration. Although tonic-clonic seizure episodes evoked by KA were unaffected, TDZD-8 pretreatment decreased KA mediated elevation in caspase-3 cleavage as well as increased Bcl2 and phospho-GSK3ß (Ser9; pGSK3ß(Ser9)) expression. Likewise, microscopic examination also revealed that pretreatment with TDZD-8 attenuated cell damage elicited by KA in the CA1, CA3 and DG regions. In all the above parameters, the combined effect of a sub-effective dose of sodium valproate (SVP) with TDZD-8 was higher than that of solitary TDZD-8 treatment. The findings suggest that activated GSK3ß orchestrated neurodegenerative alterations following KA treatment and its inhibition by TDZD-8 affords a distinct neuroprotective profile by activating Akt/GSK3ß pathway which might act upstream of Bax/Bcl2 and caspase-3 pathways. Compounds targeting GSK3ß activity might represent a novel therapeutic option for exploration as an adjunct to conventional anti-epileptic drugs in preventing neurodegenerative processes in TLE.

Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats.

In the present study, we investigated the effects of chromium picolinate (CrP) on behavioural and biochemical parameters in chronic unpredictable mild stress (CUMS) induced depression and anxiety in rats. The normal and stressed male Swiss albino rats were administered CrP (8 and 16µg/mL in drinking water), they received stressors for seven days (each day one stressor) and this cycle was repeated three times for 21 days. On 22nd day, behaviour assessments followed by biochemical estimations were conducted. The results showed that treatment of CrP produced significant antidepressant effect, which has been evidenced by decrease in immobility time in modified forced swimming test (FST) in chronic unpredictable mild stress (CUMS) induced depression in rats. In elevated plus maze (EPM), CrP (16µg/mL) showed significant reduction in time spent in open arm. CrP (8µg/mL and 16µg/mL) also showed significant decrease in number of entries in open arm that shows antianxiety effect of CrP in CUMS rats. It was also found that CrP (8 and 16µg/mL) significantly increased 5-HT concentration in the discrete regions of brain (cortex and cerebellum). On the other hand, the plasma corticosterone level was significantly decreased with CrP (16µg/mL). The results suggested that increase in the concentration of 5-HT and decrease in plasma corticosterone levels could be responsible for improvement in symptoms of depression and anxiety in CUMS induced depression and anxiety in rats.

Cardioprotective role of H3R agonist imetit on isoproterenol-induced hemodynamic changes and oxidative stress in rats.

The cardioprotective role of histamine H3 receptor (H3R) agonist imetit (IMT) in isoproterenol (ISO)-induced alterations of hemodynamic and oxidative stress was investigated in Wistar rats. In this study, rats were treated with IMT (5 and 10 mg/kg, per orally [p.o.]), carvedilol (10 mg/kg, p.o.) and ISO control group (normal saline) for 7 d, with concurrent subcutaneous administration of ISO (85 mg/kg) at 24 h interval on last two consecutive days whereas control group was administered with vehicle only. ISO significantly attenuated cardiac antioxidant enzymes superoxide dismutase, catalase and increased plasma cardiac injury biomarkers creatine kinase-MB, alanine transaminase and aspartate transaminase. ISO also altered cardiac activity as evidenced by decrease in blood pressure (34.60%) and increase in heart rate (11.40%). The damage due to oxidative stress was revealed by histopathology alterations such as myocyte necrosis, myofibrillar degeneration and pyknotic nucleus. However, pre-treatment with IMT demonstrated restoration of hemodynamic alterations along with significant preservation of antioxidants and myocyte injury-specific marker enzymes. Furthermore, protective effect of IMT was reconfirmed by the histopathological salvage of myocardium. Results of the present study demonstrated the cardioprotective potential of IMT, as evidenced by favorable improvement in ISO-induced hemodynamic, plasma cardiac biomarkers and tissue antioxidant status along with maintenance of integrity of myocardium.

Interactions of atenolol with alprazolam/escitalopram on anxiety, depression and oxidative stress.

Anxiety and depression are highly comorbid disorders possibly sharing a common neurobiological mechanism. The dysfunction of serotoninergic, noradrenergic and dopaminergic neurotransmission, abnormal regulation in the hypothalamic-pituitary-adrenal axis (HPA), disturbance of cellular plasticity including reduced neurogenesis, or chronic inflammation connected with high oxidative damage play a crucial role in the development of anxiety and depression. The present study was aimed to investigate the effects of atenolol alone and in combination with alprazolam/escitalopram on anxiety, depression and oxidative stress. Wistar albino rats were subjected to 21 day treatment of drugs then exposed to elevated-plus maze (EPM) and modified forced swim test (MFST), and oxidative stress markers were estimated in isolated brain tissue of all groups. The results indicated that atenolol in combination with alprazolam/escitalopram exhibited antidepressant effects by significantly decreasing the immobility and increasing the swimming behavior in the MFST and anti-anxiety effects by increasing the percentage preference and number of open arm entries as well as time spent in open arm in EPM. Pretreatment with atenolol alone and combination with alprazolam/escitalopram also ameliorated tissue glutathione (GSH) and decreased malondialdehyde (MDA) level significantly which explore antioxidant properties of drugs, and combination augments the therapeutic response of monotherapy in depression. In conclusion behavioral and biological findings indicate that the combination of atenolol with alprazolam/escitalopram has the potential of being highly efficacious in treating anxiety and depressive disorders as well as oxidative stress.

Neuroprotective effects of chloroform and petroleum ether extracts of Nigella sativa seeds in stroke model of rat.

PURPOSE: Stroke still remains a challenge for the researchers and scientists for developing ideal drug. Several new drugs are being evaluated showing excellent results in preclinical studies but when tested in clinical trials, they failed. Many herbal drugs in different indigenous system of medicine claim to have beneficial effects but not extensively evaluated for stroke (cerebral ischemia). AIM: The present study was undertaken to evaluate chloroform and petroleum ether extract of Nigella sativa seeds administered at a dose of 400 mg/kg, per orally for seven days in middle cerebral artery occluded (MCAO) rats for its neuroprotective role in cerebral ischemia. MATERIALS AND METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion for two hours followed by reperfusion for 22 hours. After 24 hours, grip strength, locomotor activity tests were performed in different treatment groups of rats. After completing behavioral tests, animals were sacrificed; brains were removed for the measurement of infarct volume followed by the estimation of markers of oxidative stress. RESULTS: Both chloroform and petroleum ether extracts-pretreated rats showed improvement in locomotor activity and grip strength, reduced infarct volume when compared with MCAO rats. MCA occlusion resulted in the elevation of levels of thiobarbituric acid reactive substance (TBARS), while a reduction in the levels of glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase levels were observed. Pre-treatment of both extracts of Nigella sativa showed reduction in TBARS, elevation in glutathione, SOD, and catalase levels when compared with MCAO rats. CONCLUSION: The chloroform and petroleum ether extract of Nigella sativa showed the protective effects in cerebral ischemia. The present study confirms the antioxidant, free radical scavenging, and anti-inflammatory properties of Nigella sativa already reported.

Oxcarbazepine and fluoxetine protect against mouse models of obsessive compulsive disorder through modulation of cortical serotonin and CREB pathway.

The serotonergic system is suggested to be dysregulated in obsessive compulsive disorder (OCD) as selective serotonin reuptake inhibitors have emerged as the mainstay in the treatment of this disorder. Oxcarbazepine (OXC), a second generation antiepileptic drug, enhances hippocampal serotonin (5-HT) levels. The aim of the present study was to screen the anti-OCD effects of OXC on marble burying behaviour (MBB) and 8-OHDPAT-induced disruption of alternation, two most studied paradigms of OCD, in rodents. Here we show that 8-OHDPAT (2.8 mg/kg) significantly increases spontaneous alternation behaviour (SAB) score in a T-maze. Fluoxetine (FLX), an SSRI on chronic administration (10mg/kg, 21 days) restored the increase in SAB induced by 8-OHDPAT in mice which is in line with the findings earlier reported for rats. Hence, we present the first mouse model of OCD induced by 2.8 mg/kg of 8-OHDPAT. Chronic administration (21 days) of OXC (20 and 40 mg/kg) also restored the SAB disrupted by 8-OHDPAT which was comparable to FLX. Likewise in MBB test, FLX and OXC significantly reduced the number of marbles buried. 8-OHDPAT induced OCD was associated with a concomitant decrease in basal 5-HT levels (88%) and depletion of basal CREB (32%) in the frontal cortex. Chronic treatment with FLX and OXC effectively mitigated the lowering effects of 8-OHDPAT on cortical 5-HT, and enabled an efficient recovery in basal CREB levels. Our results on FLX and OXC provide the indication that their anti-OCD effects in part, might be elicited through modulation of 5HT levels and CREB pathway.

Cardioprotective potential of simvastatin in the hyperhomocysteinemic rat heart.

The present study investigated the probable role of simvastatin, 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, in abrogated cardioprotection in hyperhomocysteinemic (Hhcy) rat hearts. Isolated Langendorff's perfused normal and Hhcy rat hearts were subjected to 30-min global ischemia (I) followed by 120-min reperfusion (R). Assessment of myocardial damage was done by measuring infarct size and analyzing the release of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in coronary effluent. In addition, the oxidative stress in the heart was assessed by measuring lipid peroxidation and superoxide anion generation. I/R produced myocardial injury in normal and Hhcy rat hearts by increasing myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Hhcy rat hearts showed enhanced myocardial injury and high oxidative stress as compared to normal hearts. Treatment with Simvastatin (10 µMol) afforded cardioprotection against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts as assessed in terms of reductions in myocardial infarct size, LDH and CK levels in coronary effluent and oxidative stress. The reductions in the high degree of oxidative stress may be responsible for the observed cardioprotection afforded by simvastatin against I/R-induced myocardial injury in normal and hyperhomocysteinemic rat hearts.

Protective effects of histamine H3-receptor ligands in schizophrenic behaviors in experimental models.

Schizophrenia (SCZ) afflicts around 1% of the world's population with characteristic symptoms such as hallucinations, delusions, and cognitive disorders. Several experimental studies in the past have indicted brain histaminergic neuronal system involvement in the pathogenesis of psychotic disorders including SCZ. Present study investigates anti-schizophrenic activity using two histamine H(3)-receptor (H(3)R)-antagonists/inverse agonists, ciproxifan (3.0 mg/kg, i.p.) and clobenpropit (15 mg/kg, i.p.), on some of the established animal model of schizophrenia, for example, amphetamine (AMPH) and dizocilpine (MK-801)-induced hyperactivity, apomorphine (APO)-induced climbing behavior, scopolamine and MK-801-induced learning and memory deficits and haloperidol-induced catalepsy including determination of acetylcholinesterase (AChE) activity. Results of the present study demonstrate that ciproxifan and clobenpropitwere able to control AMPH and MK-801-induced hyperlocomotor activities demonstrated as reduced horizontal activity and reduced number of movements made by rats. Further, there was overall reduction in APO-induced climbing behavior. Learning and memory deficits, as evaluated on elevated plus maze, followed by estimation of brain AChE activity demonstrated positive results with these protypical imidazole H(3)R-antagonists/inverse agonists.

Ameliorating effects of two extracts of Nigella sativa in middle cerebral artery occluded rat.

PURPOSE: Aqueous and hydroalcoholic extracts of Nigella sativa (400 mg/kg, orally) for 7 days were administered and evaluated for their neuroprotective effects on middle cerebral artery occluded (MCAO) rats. MATERIALS AND METHODS: Cerebral ischemia was induced by middle cerebral artery occlusion for 2 h followed by reperfusion for 22 h. After 24 h of ischemia, grip strength, locomotor activity tests were performed in the surgically operated animals. After behavioral tests, animals were immediately sacrificed. Infarct volumes followed by the estimation of markers of oxidative stress in the brains were measured. RESULTS: Locomotor activity and grip strength of animals were improved in both aqueous and hydroalcoholic extracts pretreated rats. Infarct volume was also reduced in both extracts pretreated rats as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione and antioxidant enzymes, viz., superoxide dismutase (SOD) and catalase levels were observed following MCAO. Pretreatment of Nigella sativa extracts showed the reduction in TBARS, elevation in glutathione, SOD and catalase levels as compared with MCAO rats. CONCLUSION: The present study observed the neuroprotective effects of both the extracts of Nigella sativa in cerebral ischemia. The neuroprotective effects could be due to its antioxidant, free radical scavenging, and anti-inflammatory properties.

Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice.

Anxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days' pre- and 7 days' post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hearts were dissected out for estimation of thiobarbituric acid reactive substance and Transmission Electron Microscopy (TEM) studies. Our results showed that DOX administration induced cardiomyopathy in mice. This was evidenced by an increased serum LDH and tissue malondialdehyde (MDA) and was confirmed by TEM studies. Alprazolam treatment for 14 days dose dependently reversed DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Furthermore, alprazolam also reversed the anxiety-like effects induced by DOX in both the tests for anxiety. Thus, alprazolam appears to be a good candidate for alleviating anxiety in patients following MI or HF.