Protective Effect of Combined Long Time Administration of Selenium and Vitamin C on Liver and Kidney Toxicity of Cadmium in Rats.

BACKGROUND & OBJECTIVE: Increased industrial activities leads to prolonged human exposure to industrial pollutant such as cadmium (Cd). |Chronic exposure to Cd in Mammals and also human being, can cause damages to various organs and particularly kidneys and liver. The goal of this study was to investigate the prophylactic effects of combined selenium (Se) and ascorbic acid supplement in rat cadmium toxicity. METHODS: Sixty adult male Wistar rats were divided to 10 groups: one control, one sham and two clusters of 4 intervention groups which were fed with 1 or 5 mg Cd /kg water, for 28 days. Ascorbic acid supplement was added to drinking water of four groups (10 mg/L). Four groups received intraperitoneal Se (1 mg/kg) at day 1, 5, 10, 15, 20 and 25. Finally, Cd concentration was measured by atomic absorption spectrophotometry in liver and kidney sections. Furthermore, pathological changes were investigated in these sections. RESULTS: The results showed weight gain in Cd groups which received ascorbic acid and Se, in contrast to weight loss in parallel groups without vitamin C and Se. The stronger necrosis and inflammation have been observed in group received 5 mg/kg Cd compared to group with 1 mg/kg Cd (P<0.05). In addition, cadmium level was higher in untreated groups without any supplements, significantly (P<0.05). CONCLUSION: Drinking water with ascorbic acid may have prophylactic effects across cadmium, and combination of Se and ascorbic acid are associated with higher prophylactic effects in both kidney and liver in rats to decrease the Cd toxicity.

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats.

It has been proposed carbon tetrachloride (CCl4 ) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl4 -induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl4 (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl4 significantly inhibited alterations in the serum levels of AST, ALP (** P < 0.01), and ALT (*** P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl4 -induced hepatotoxicity in rats.

Antibiofilm activity of natural zeolite supported NanoZnO: inhibition of Esp gene expression of Enterococcus faecalis.

AIM: To evaluate the antibiofilm effect and esp gene downregulation of Enterococcus faecalis through nanozinc oxide fabricated on natural zeolite (NanoZnO/Ze). Materials & methods:Zeolite and NanoZnO/Ze materials were characterized by x-ray diffraction, x-ray fluorescence and field emission scanning electron microscopy coupled with energy dispersive x-ray. Atomic absorption spectroscopy was used to evaluate zinc release. E. faecalis biofilm formation and its esp gene expression were assessed under nanocomposite treatment. RESULTS: Spherical-shaped ZnO nanoparticles with an average size of 30 nm were dispersed on the zeolites surface. The leakage of cationic zinc from NanoZnO/Ze displayed a long lasting and considerable release content (p < 0.0001) compared with ZnO/Ze. NanoZnO/Ze effectively inhibited (p < 0.0001) biofilm formation and affected esp gene downregulation of E. faecalis. CONCLUSION: Our results show that NanoZnO/Zeolite can potentiate against biofilm infections due to E. faecalis and possibly other pathogens.

Combination therapy profoundly improved skin flap survival by modulating KATP channels and nitric oxide.

PURPOSE: A potential therapeutic approach on skin flap necrosis is to target parallel pathways involved in necrosis. Azelaic Acid, Minoxidil and Caffeine combination was tried on skin flap survival by their possible interaction with ATP sensitive potassium (KATP) channels and nitric oxide pathway. MATERIAL AND METHODS: Sprauge-Dawley rats were divided into 8 groups for skin flap surgery. Azelaic acid, minoxidil, caffeine, or their combination were applied topically in different groups. Two additional groups were treated with L-NAME or glibenclamide in addition to the combination therapy. Percentage of flap necrosis was calculated and flap samples were removed to measure tissue malondialdehyde (MDA) and nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS), Bcl-2 and Bax proteins. RESULTS: Combination therapy profoundly decreased skin flap necrosis, tissue MDA contents, and expression of the pro-apoptotic protein Bax (p < 0.05 vs. single treatments). These effects were reversed by L-NAME and glibenclamide pre-treatments. Further evaluations showed combination therapy increases flap tissue NO content and iNOS expression (p < 0.05 vs. single treatments). CONCLUSION: Beneficial effect of the combination therapy with azelaic acid, minoxidil and caffeine therapy on rescuing the flap from necrosis by targeting parallel signaling pathways suggested potential applications in clinical practice.

The potassium channel blocker, dalfampridine diminishes ouabain-induced arrhythmia in isolated rat atria.

The aim of the present experiment was to investigate the possible antiarrhythmic effects of dalfampridine in ouabain-induced arrhythmia in rats. Twenty-four male rats including the control and dalfampridine-incubated (100 µM to 10 mM) ouabain-stimulated (40 µM) groups were used. After induction of anesthesia, the atria were isolated and the time of onset of arrhythmia and asystole were recorded. The contractile force of atria was also measured. Dalfampridine at concentration of 1 mM significantly postponed the onset of arrhythmia and asystole compared to control group (p ≤ .05). Ouabain significantly increased the atrial beating rate in control group (p ≤ .05), while pretreatment of isolated atria with dalfampridine reversed this effect. Incubation of isolated atria with ouabain did not alter the contractile force in both control- and dalfampridine-treated groups (p > .05). It is concluded that dalfampridine might possess antiarrhythmic properties in reducing the atrial arrhythmias.

Cardiac chronotropic hypo-responsiveness and atrial fibrosis in rats chronically treated with lithium.

Lithium is a widely used mood-stabilizing agent; however, it causes a variety of cardiovascular side effects including sinus node dysfunction. In this study we explored the potential adverse effects of lithium on cardiac chronotropic responsiveness, atrial tissue histology and gene expression in rats that were chronically treated with therapeutic doses of lithium. Male Wistar albino rats were given lithium chloride (2.5 g/kg) orally for 2 or 3 months. Following treatment, the atria were isolated and spontaneously beating rate and chronotropic responsiveness to ß-adrenergic stimulation was evaluated in an organ bath. Development of cardiac fibrosis was examined by histological methods. The expression of atrial Col1a1 (collagen I, alpha 1) and ß-arrestin2 was also assessed using quantitative RT-PCR. Treatment with lithium induced a significant hypo-responsiveness to adrenergic stimulation (P < 0.001) and caused fibrosis in the atrial tissue of treated rats. In addition, the expression of atrial Col1a1 mRNA was significantly increased in atrial tissues of lithium-treated animals, while ß-arrestin2 mRNA expression did not show a significant difference compared with control animals. Altogether, these findings indicate that cardiac chronotropic hypo responsiveness and associated cardiac fibrosis are side effects of chronic lithium treatment. Moreover, it seems that lithium treatment does not influence ß-arrestin2 mRNA expression.

Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats.

The main vascular feature in endotoxemia is impaired contractile responses to vasoactive agents. We study the aortic response to 5HT11 A, 5HT1B1D and 5HT2A receptors agonist and antagonist in chronic endotoxemic rats. Intraperitoneal injection of 1 mg/kg lipopolysaccharide for 5 days induced chronic endotoxemia. Control rats received intraperitoneal injection of 1 ml/kg saline for 5 days. Rats divided into 3 groups. In first, DOI2 hydrochloride used as an agonist and sarpogrelate hydrochloride as an antagonist of 5HT2A receptor. In second, (R)-(+)-8-OH-DPAT3 and WAY1001354 used as an agonist and antagonist of 5HT1A receptor respectively. In third, Zolmitriptan used as an agonist and GR127935 hydrochloride as an antagonist of 5HT1B1D receptor. Aorta Isolated for organ bath study. Real time-PCR5 and histopathological study examined receptors gene expression and protein localization. Cumulative 8-OH-DPAT caused relaxation in control aorta (EC506 7.79±21.35 and 8.53±10.74 with and without antagonist), which was enhanced in endotoxemia (EC50 6.35±8.48 and very wide±17.38 with and without antagonist). Cumulative zolmitriptan caused relaxation in control aorta (EC50 very wide±8.65 and 8.38±8.44 with and without antagonist), which was enhanced in endotoxemia (EC50 very wide±9.53 and 8.37±13.49 with and without antagonist). DOI hydrochloride contracted the control aorta (EC50 6.51±7.14 and 5.98±1.65 with and without antagonist), which was converted to relaxation in endotoxemic group (EC50 infinity±80.43 and 7.37±20.28 with and without antagonist). PCR studies revealed enhanced 5HT1A receptor and diminished 5HT1B1D and 5HT2A receptor genes expression, while histopathological studies showed inflamed, damaged endothelium in endotoxemic aorta. Our data supports enhanced vasodilation and impaired vasoconstriction during endotoxemia.

Sildenafil protective effects on high glucose-induced neurotoxicity in PC12 cells: the role of oxidative stress, apoptosis, and inflammation pathways in an in vitro cellular model for diabetic neuropathy.

Objectives Diabetic neuropathy (DN) induces lifetime disability and there is currently no effective therapy to treat or to minimize patients suffering, so it is thereby imperative to develop therapeutic strategies for this disease. Since oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial mechanisms in development and progression of DN, it is important to explore tools by which one can reduce factors related to these pathways. Herein, the understandings of the sildenafil neuroprotective effect through increase of cGMP level and the mediation of oxidative stress, apoptosis, and inflammation pathways on neurotoxicity induced by high glucose (HG) in PC12 cells as an in vitro cellular model for DN were investigated. Methods We reported that the PC12 cells pre-treatment with sildenafil (0.008 µM) for 60 min and then exposing the cells to HG (25 mM for 72 h) or normal glucose (NG) (5 mM for 72 h) condition, show: Results (1) significant attenuation in reactive oxygen species, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, mitochondrial membrane potential, and ATP levels. Conclusion All these data together led us to propose neuroprotective effect of sildenafil is probably through its antioxidant, antiapoptotic, and anti-inflammatory activities. Of course, further studies are required to explain the underlying mechanism of the sildenafil effects.

Involvement of IL-1ß and IL-6 in antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in rats.

PURPOSE: Evidence show that statins possess wide beneficial cardioprotective and anti-inflammatory effects; therefore, in the present experiment, we investigated the antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in isolated rat atria and the role of several inflammatory cytokines in this effect. MATERIALS AND METHODS: Male rats were pretreated with either of atorvastatin (10 mg/kg) or vehicle, orally once daily for 6 weeks. After induction of anesthesia, we isolated the atria and after incubation with ouabain, time of onset of arrhythmia and asystole as well as atrial beating rate and contractile force were recorded. We also measured the atrial levels of IL-1ß, IL-6, and TNF-α after the injection of ouabain to animals. RESULTS: Pretreatment with atorvastatin significantly delayed the onset of arrhythmia and asystole compared with vehicle-treated group (p < .01, p < .001, respectively). Incubation of ouabain boosted both atrial beating rate and contractile force in vehicle-treated group (p < .05), while these responses in atorvastatin-treated group were not significant (p > .05). Injection of ouabain elevated the atrial levels of IL-1ß, IL-6, and TNF-α, while pretreatment of animals with atorvastatin could reverse the ouabain-induced increase in atrial IL-1ß and IL-6 (p < .01 and p < .05, respectively). CONCLUSIONS: It is concluded that observed antiarrhythmic effects of atorvastatin might be attributed to modulation of some inflammatory cytokines, at least IL-1ß and IL-6.

Histopathological Evaluation of the Effectiveness of Glycyrrhizic Acid as a Radioprotector Against the Development of Radiation-Induced Lung Fibrosis.

BACKGROUND: Radiotherapy of the thorax often causes lung inflammation leading to fibrosis. OBJECTIVES: The aim of this study was to investigate whether the use of glycyrrhizic acid (GLA) could improve the development of lung fibrosis in irradiated animals. MATERIALS AND METHODS: Wistar rats were divided into four groups. Group A rats received thoracic irradiation. Rats in group B received GLA and irradiation. Group C received GLA and no irradiation. Group D received no GLA and irradiation. GLA was administered at a dose of 4 mg/kg body weight using an intraperitoneal injection one hour before thoracic irradiation. Radiation therapy was delivered on a Cobalt-60 unit using a single fraction of 16 Gy. The animals were sacrificed at 32 weeks following thoracic irradiation. The lungs were dissected and blind histopathological evaluation was performed. RESULTS: Histopathologically, a decrease (statistically not significant) in the thickening of alveolar or bronchial wall, formation of fibrous bands, and superimposed collagen were noted in the animals in group B as compared to the animals in group A. CONCLUSION: In this experimental study, administration of GLA one hour before thoracic irradiation may be a protective agent against radiation-induced fibrosis in animals and this model could be used in future studies.

Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test.

BACKGROUND: Previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (KATP), in the present study we investigated the involvement of KATP channels in antidepressant-like effect of baclofen in the forced swimming test (FST). METHODS: After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of KATP channels, after determination of sub-effective doses of glibenclamide as a KATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. RESULTS: Baclofen at dose 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant-like effect of baclofen (1mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. CONCLUSIONS: Our study for the first time revealed that antidepressant-like effect of baclofen on mice is KATP-dependent, and baclofen seems that exert this effect by blocking the KATP channels.

The effect of nitrazepam on depression and curiosity in behavioral tests in mice: The role of potassium channels.

Evidence show that gamma-aminobutyric acid (GABA) receptors are involved in depression, so the aim of this study was to investigate the effect of nitrazepam as agonist of GABAA receptors on depression and curiosity in male mice and the role of potassium channel in antidepressant-like response. For this purpose, we studied the antidepressant-like properties of fluoxetine, nitrazepam, glibenclamide, and cromakalim by both forced swimming test (FST) and tail suspension test (TST). Animals were injected by various doses of nitrazepam (0.05, 0.1, and 0.5mg/kg). Nitrazepam at dose of 0.5mg/kg significantly decreased the immobility time compared to control group in both FST and TST. Fluoxetine also showed such a response. Co-administration of nitrazepam (0.05mg/kg) with glibenclamide in TST (1mg/kg) and in FST (0.3, 1mg/kg) also showed antidepressant-like response. Beside, cromakalim (0.1mg/kg) could reverse the antidepressant-like effect of nitrazepam (0.5mg/kg) in both FST and TST, while cromakalim and glibenclamide alone could not change the immobility time compared to control group (P>0.05). The hole-board test revealed that nitrazepam at doses of 0.5 and 0.1mg/kg could increase the activity of the animal's head-dipping and boost the curiosity and exploration behavior of mice. The results of this study revealed that nitrazepam may possess antidepressant-like properties and this effect is dependent to potassium channels in both FST and TST.

Impacts of morphine addiction on spermatogenesis in rats.

BACKGROUND: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. OBJECTIVE: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. MATERIALS AND METHODS: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection) and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. RESULTS: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p<0.05). Histological studies revealed that changes in different groups of opioid application might affect sperm formation. Sperm count in morphine group was (0±0) and in naloxone group, naloxone+morphine, sham and control were 235±3.77, 220±3.81, 247.12±6.10 and 250±6.54, respectively (p<0.001). CONCLUSION: Morphine could affect all spermatogenesis stages.

Involvement of Inflammatory Cytokines in Antiarrhythmic Effects of Clofibrate in Ouabain-Induced Arrhythmia in Isolated Rat Atria.

Considering the cardioprotective and anti-inflammatory properties of clofibrate, the aim of the present experiment was to investigate the involvement of local and systemic inflammatory cytokines in possible antiarrhythmic effects of clofibrate in ouabain-induced arrhythmia in rats. Rats were orally treated with clofibrate (300 mg/kg), and ouabain (0.56 mg/kg) was administered to animals intraperitoneally. After induction of anesthesia, the atria were isolated and the onset of arrhythmia and asystole was recorded. The levels of inflammatory cytokines in atria were also measured. Clofibrate significantly postponed the onset of arrhythmia and asystole when compared to control group (P ≤ 0.05 and P ≤ 0.01, resp.). While ouabain significantly increased the atrial beating rate in control group (P ≤ 0.05), same treatment did not show similar effect in clofibrate-treated group (P > 0.05). Injection of ouabain significantly increased the atrial and systemic levels of all studied inflammatory cytokines (P ≤ 0.05). Pretreatment with clofibrate could attenuate the ouabain-induced elevation of IL-6 and TNF-α in atria (P ≤ 0.01 and P ≤ 0.05, resp.), as well as ouabain-induced increase in IL-6 in plasma (P ≤ 0.05). Based on our findings, clofibrate may possess antiarrhythmic properties through mitigating the local and systemic inflammatory factors including IL-6 and TNF-α.

Prostaglandin F2α modulates atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.

Endotoxemia induces various physiological adaptive responses such as tachycardia. There is evidence to show that inflammatory tachycardia might be linked to a direct action of prostanoids on the cardiac pacemaker cells. Recent reports have indicated that systemic inflammation may uncouple of cardiac pacemaker from cholinergic neural control in experimental animals; however, the exact mechanism of this phenomenon is uncertain. This study was aimed to explore the hypothesis that prostanoids modulate atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats. Male albino rats were given intraperitoneal injection of either saline or lipopolysaccharide (LPS, 1 mg/kg). 3 h after saline or LPS injection, the atria were isolated and chronotropic responsiveness to cholinergic stimulation was evaluated in an organ bath. The expression of atrial cyclooxygenases (COX)-1, COX-2 and COX-3 mRNA was assessed by quantitative real-time RT-PCR and cytosocalcium-dependent phospholipase A2 (cPLA2) activity was measured in the atria. The expression of atrial COX-2 mRNA and cPLA2 activity increased significantly in endotoxemic atria (P<0.05). Incubation with prostaglandin F2α (PGF2α, 100 pM) could significantly decrease chronotropic response to cholinergic stimulation in vitro. Likewise, LPS injection could induce a significant hyporesponsiveness to cholinergic stimulation, and incubation of isolated atria with either indomethacin (5 µM) or AL-8810 (a PGF2α antagonist, 10 µM) could reverse it (P<0.01, P<0.05, respectively), while SQ29548 (a thromboxane A2 antagonist, 10 nM) was failed (P>0.05). Our data showed that PGF2α may contribute to the atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.

Teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses.

Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied. Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P ≤ 0.01). It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.

Effects of calci soya balance and vitagnus on menopausal symptoms.

BACKGROUND: Menopause is a period of women's lives with changes and symptoms that affect their work, sleep and quality of life. Therefore, it is important to overcome these symptoms. OBJECTIVES: The aim of the present study was to compare the effects of Calci soya balance and Vitagnus on menopausal symptoms. PATIENTS AND METHODS: This double-blinded controlled trial study was performed in public health centers of Tehran University of Medical Sciences (2011-2012). Seventy postmenopausal women with menopausal symptoms were randomly divided into two groups of treatments with Vitagnus and Calci soya balance. Data were collected using interviews, answering Cooperman's index questionnaires before four and eight weeks after the treatment. Descriptive and analytic statistics were used for analyzing the data. RESULTS: In both groups, Wilcoxon test showed a significant decrease in the mean of Cooperman's menopausal index as well as after four and eight weeks of treatment (P = 0.000). Mann-Whitney test did not show any significant differences between the two groups, before and after four and eight weeks of treatment. CONCLUSIONS: The results showed that both Vitagnus and Calci soya balance were effective on reduction of menopausal symptoms to a similar extent and medical community can administer each of these two drugs based on patients' conditions and costs.

The Study of Analgesic Effects of Leonurus cardiaca L. in Mice by Formalin, Tail Flick and Hot Plate Tests.

Leonurus cardiaca, commonly known as motherwort, is a member of the Lamiaceae family. It has a number of interesting biological activities, for example, sedative and hypotensive, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of the present study was to investigate the effect of alcoholic extract of aerial part of Leonurus cardiaca on nociceptive response using formalin, tail flick, and hot plate tests in mice. The acute treatment of mice with an ethanolic extract at doses of 500 and 250 mg/kg by intraperitoneal administration produced a significant antinociceptive in the first and second phases of formalin test, respectively. The hot plate and tail flick tests showed an increase in the antinociceptive effect at dose 500 mg/kg. These results suggest that Leonurus cardiaca possesses central and peripheral antinociceptive actions.

The role of clomipramine in potentiating the teratogenic effects of caffeine in pregnant rats: a histopathological study.

Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5 mL of normal saline. Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P ≤ 0.001). This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.

Effects of lithium on peripheral neuropathy induced by vincristine in rats.

Vincristine (VCR) as a frequently used antimitotic agent which is commonly prescribed for wide spectrum of neoplasm, causes mixed sensorimotor neuropathy. Several evidences show lithium could be a neuroprotective agent, therefore to assess whether a pretreatment and at subtherapeutic dose it could prevent the peripheral neuropathy produced by VCR, rats were treated with VCR 0.1mg/kg i.p. for 3 alternative doses and / or lithium chloride (20mg/kg or 40 mg/kg i.p. daily from the first day to the day of sacrifice). Erythrocyte lithium concentration (ELC) and plasma lithium concentration (PLC) were measured at the seventh day of study and the day of scarification. After seventh day of lithium administration, PLC and ELC reached to a steady state at subtheraputic dose and they did not significantly change at normal housing situation. Hot plate, open field test and nerve conduction velocity were used to evaluate the sensory and motor neuropathy. Only VCR treated rats showed behavioral, electrophysiological and histological evidences of a mixed sensorimotor neuropathy by significant increase in hot plate latencies and a marked decrease in total distance moved and conduction velocities in both sensory and motor nerves. Lithium at the dose of 20mg/kg and specially 40mg/kg robustly reduced the rate of mortality, general toxicity and was able to ameliorate mixed sensorimotor neuropathy induced by VCR. These results suggest that lithium at dose of 20mg/kg and 40 mg/kg, potentially by its effects on cell survival pathways such as inhibition of glycogen synthase kinase-3 (GSK3ß), can prevent both motor and sensory components of VCR neuropathy.