Hesperidin neuroprotective effects against carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) is produced via incomplete combustion of fossil fuels and it may cause long-term neurological sequel upon exposure. Hesperidin (HES), a flavanone glycoside found in citrus plants, exerts diverse beneficial health effects. The present study mechanistically examined the neuroprotective effects of HES in CO-poisoned rats. Thirty male Wistar rats (five groups of six animals) were exposed to 3000 ppm CO for 1 h. Immediately after the exposure and on the next 4 consecutive days (totally five doses), rats intraperitoneally received either normal saline (the control group) or different doses of HES (25, 50, and 100 mg/kg). A sham group that was not exposed to CO was also considered. After evaluation of spatial learning and memory using a Morris water maze (MWM), animals were sacrificed and oxidative stress status in blood samples, and Akt, Bax, Bcl2, and brain-derived neurotrophic factor (BDNF) expression in brain samples were assessed. Western blot analysis indicated increased Akt but decreased Bax/Bcl2 levels in the HES 100 mg/kg, and induced BDNF levels in all HES-treated groups. MWM results showed that HES significantly decreased memory loss. The current findings indicate that HES could alleviate neurological impairments induced by CO in rats.

Hormetic effects of curcumin on oxidative stress injury induced by trivalent arsenic in isolated rat hepatocytes.

Objective: Arsenic (As) poisoning is a worldwide public health problem. Arsenic can cause cancer, diabetes, hepatic problems, etc. Hence, we investigated possible hepatoprotective properties of curcumin against As3+-induced liver damages in freshly isolated rat hepatocytes. Materials and Methods: Isolation of hepatocytes was done by the two-step liver perfusion method using collagenase. The EC50 concentration of As3+ was used in toxicity assessments and curcumin (2, 5, and 10 µM) was added 15 min before As3+ addition to isolated hepatocytes. Curcumin impact was assessed in terms of cytotoxicity, lipid peroxidation induction, reactive oxygen species (ROS) levels, and mitochondrial membrane potential. Results: As3+ significantly increased cytotoxicity, malondialdehyde and ROS levels and induced mitochondrial membrane damage and hepatocyte membrane lysis after 3 hr incubation. Curcumin 2 µM significantly prevented lipid peroxidation induction, ROS formation, and mitochondrial membrane damage; while curcumin 5 µM had no apparent effect on these parameters, curcumin 10 µM potentiated them. Conclusion: Curcumin only at low doses could ameliorate oxidative stress injury induced by As3+ in isolated rat hepatocytes.

Effects of gallic acid on intraperitoneal adhesion bands in rats.

Objective: Gallic acid (GA) is an organic acid that possesses anti-inflammatory effects as it inhibits the production of metalloproteinases, tissue plasminogen activator, growth factors and adhesion molecules. Since formation of abdominal surgery-induced adhesion bands is accompanied by inflammation, angiogenesis and cell proliferation, in the current study, we assessed potential beneficial properties of GA against adhesion bands formation in rats. Materials and Methods: Thirty-six adult male rats were assigned into six groups of six animals. After induction of anesthesia, peritoneal injury was induced using a standard method and animals received either GA (10, 25, 50 and 100 mg/kg), or normal saline, while a group of rats remained intact. Seven days after the surgery, animals were decapitated and samples were collected for pathology evaluations. Also, lipid peroxidation (TBARS) and tumor necrosis factor alpha (TNF-α) levels were determined in serum samples. Results: Our results showed that GA significantly reduced lipid peroxidation in serum samples but had no effect on TNF-α levels. Furthermore, microscopic and macroscopic injuries reduced significantly in GA-treated animals. Conclusion: Since GA reduced adhesion bands formation at microscopic and macroscopic levels, it could be considered a treatment against adhesion bands formation.

Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze.

OBJECTIVES: H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. METHODS: Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 µg/µL, dissolved in saline) or O-acetyl-L-carnitine (100 µM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. RESULTS: The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. CONCLUSIONS: Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

Effects of Quercetin and Resveratrol on Zinc Chloride- and Sodium Metavanadate-Induced Passive Avoidance Memory Retention Deficits in Male Mice.

Quercetin and resveratrol are found in a variety of fruits and vegetables and have several biological and pharmacological properties. In this study, the effects of quercetin [50 mg/kg, intraperitoneal (i.p.)] and resveratrol (50 mg/kg, i.p.) on zinc chloride (ZnCl2; 75 mg/kg/d, 2 weeks oral gavage) and sodium metavanadate (SMV; 22.5 mg/kg/d, 2 weeks oral gavage) induced passive avoidance memory retention were investigated in step-through passive avoidance tasks. ZnCl2 was dissolved in saline and SMV was dissolved in drinking water. Mice received ZnCl2 or SMV orally for two weeks and were administered quercetin or resveratrol by i.p. injection on day 14, days 12 and 14, or days 10, 12, and 14. At the end of treatment, animals were trained for one day in a step-through passive avoidance task, then alterations in avoidance memory retention were evaluated after 24, 48, 96, and 168 h. Oral consumption of ZnCl2 and SMV decreased latency time compared with control groups. Both quercetin and resveratrol (50 mg/kg, i.p.) prevented ZnCl2- and SMV-induced avoidance memory retention impairments and did not significantly alter muscle strength, as demonstrated in rotarod tasks. No significant differences were observed between mice who received single, double, or triple doses of quercetin or resveratrol. The results suggest that quercetin and resveratrol may have preventive effects on ZnCl2- and SMV-induced memory impairment in male mice.

Tadalafil Reversed H-89 - and Scopolamine - Induced Spatial Learning Impairments in Male Rats.

Accumulated evidence shows that the cAMP and cGMP signaling pathway plays an important role in memory function and neuronal plasticity. Phosphodiesterase 5 (PDE5) is a hopeful therapeutic target in AD (Alzheimer disease), and PDE5 inhibition may be a good therapeutic strategy for the treatment of AD. In the present study, the four-day bilateral intra-hippocampal infusion of H-89 as a protein kinase AII inhibitor (10 µM/side) and intra-peritoneal injections of tadalafil (20 mg/kg) and scopolamine (0.5 mg/kg) alone and also on combination on spatial learning in Morris water maze (MWM) were investigated. DMSO and saline were used as controls for H-89 and other mentioned drugs, respectively. Rats were trained for 4 days; each day included one block of four trials. Post- training probe trial tests were performed on day 5. Administration of H-89 and scopolamine led to a significant impairment in spatial learning compared to their related controls. But, combination of tadalafil/H-89 or tadalafil/scopolamine reversed H-89 or scopolamine- induced spatial learning deficits in MWM. Taken together, these results showed the probable regulatory effects of cGMP on cholinergic and cAMP/PKA signaling pathways in co-administrations of these mentioned drugs on spatial learning in MWM.

Knowledge, attitude, and practice of pharmacy and medical students regarding self-medication, a study in Zabol University of Medical Sciences; Sistan and Baluchestan province in south-east of Iran.

BACKGROUND: Self-medication is defined as using medicinal products to treat the disorders or symptoms diagnosed by oneself. Although informed self-medication is one of the ways to reduce health care costs, inappropriate self-treatment can pose various risks including drug side effects, recurrence of symptoms, drug resistance, etc. The purpose of this study was to investigate the knowledge, attitude, and practice of pharmacy and medical students toward self-medication. METHODS: This study was conducted in Zabol University of Medical Sciences in 2018. Overall, 170 pharmacy and medical students were included. A three-part researcher-made questionnaire was designed to address the students' knowledge, attitude, and practice. Statistical analysis was performed in SPSS 25 software. RESULTS: According to the results, 97 (57.1%) students had carried out self-medication within the past 6 months. Overall, the students self-medicated on average 4.2 ± 2.9 times per year. Self-medication was more common in male students (65.4%, P = 0.043). Cold was the most common ailment treated with self-medication (93.2%), and antibiotics (74.4%) were the most commonly used drugs. The primary information sources used by the students were their previous prescriptions (47.4%). Pharmacy students had a higher level of drug information (P < 0.001). There was a statistically significant association between the level of drug information and the tendency for self-medication (P = 0.005). Disease recurrence was the most common negative complication of self-medication. CONCLUSION: There is a need to educate pharmacy and medical students regarding self-medication and its side effects. The high prevalence of self-medication and the overuse of antibiotics can pose a significant risk of drug resistance.

Effect of Two Different Doses of Vitamin D Supplementation on Uterine Myoma on South East Iranian Population: A Clinical Trial.

Objective: Uterine myoma is the most common benign tumor however with significant distress and reduced quality of life in affected women. Besides, vitamin D deficiency may be a risk factor for uterine myoma. This study aimed to evaluate the effect of vitamin D supplements on the size of myoma in women with vitamin D insufficiency or deficiency. Materials and methods: This clinical trial was conducted in a teaching hospital from 2019 to 2020. According to baseline vitamin D level, participants were assigned into two interventional equal groups (vitamin D deficiency or insufficiency) to receive either 1000 IU daily or 50000 IU weekly vitamin D for 12 weeks. The size and location of the uterine myoma were compared before and after the intervention. Results: Totally, 137 women with uterine myoma were enrolled. Based on baseline vitamin D level, 52 cases had vitamin D insufficiency and 85 cases had vitamin D deficiency. No significant difference was observed in age and BMI in both groups. The location of the subserosal and intramural myoma did not differ, otherwise, the percent of the submucosal myomas were increased significantly (p=0.020) after the intervention. In both groups decreased myoma size otherwise not significant was seen after the intervention (p=0.148 and p=0.664 respectively). Conclusion: Vitamin D supplementation may not be effective in women with vitamin D insufficiency or deficiency in the short term to reduce myoma size.

Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells.

Glyoxal (GO), a by-product of glucose auto-oxidation, is involved in the glycation of proteins/ lipids and formation of advanced glycation (AGE) and lipoxidation (ALE) end products. AGE/ALE were shown to contribute to diabetic complications development/progression such as nephropathy. Diabetic nephropathy progression has an oxidative nature. Given the antioxidant effects of polyphenols, potential protective effects of resveratrol, curcumin and gallic acid, in rat renal cells treated with GO, were evaluated in the present work. According to our results, incubation of GO with the cells reduced their viability and led to membrane lysis, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential collapse, and lysosomal membrane leakage. These findings were prevented by pre-treatment with resveratrol, curcumin and gallic acid. Mitochondrial and lysosomal toxic interactions appear to worsen oxidative stress/cytotoxicity produced by GO. Resveratrol, curcumin and gallic acid inhibited ROS formation and attenuated GO-induced renal cell death.

Magnesium sulfate ameliorates carbon monoxide­induced cerebral injury in male rats.

Carbon monoxide (CO) has been shown to induce several cardiovascular abnormalities, as well as necrosis, apoptosis and oxidative stress in the brain. Magnesium sulfate (MS) has been shown to have beneficial activities against hypoxia in the brain. In the present study, the possible protective effects of MS against CO­induced cerebral ischemia were investigated. For this purpose, 25 male Wistar rats were exposed to 3,000 ppm CO for 1 h. The animals were divided into 5 groups (n=5 in each group) as follows: The negative control group (not exposed to CO), the positive control group (CO exposed and treated with normal saline), and 3 groups of CO­exposed rats treated with MS (75, 150 and 300 mg/kg/day) administered intraperitoneally for 5 consecutive days. On the 5th day, the animals were sacrificed and the brains were harvested for the evaluation of necrosis, apoptosis and oxidative stress. Histopathological evaluation revealed that MS reduced the number and intensity of necrotic insults. The Bax/Bcl2 ratio and malondialdehyde (MDA) levels were significantly decreased in a dose­dependent manner in the MS­treated rats compared to the positive control group, while a significant dose­dependent increase in Akt expression, a pro­survival protein, was observed. In addition, MS administration reduced pro­apoptotic indice levels, ameliorated histological insults, favorably modulated oxidative status and increased Akt expression levels, indicating a possible neuroprotective effect in the case of CO poisoning. On the whole, the findings of this study indicate that MS may prove to be useful in protecting against CO­induced cerebral injury.

Interactive involvement of hippocampal cAMP/PKA and cyclooxygenase-2 signaling pathways in spatial learning in the Morris water maze.

INTRODUCTION: Accumulated evidence shows that the cAMP-PKA signaling pathway plays a key role in memory functions. Cyclooxygenase-2, a critical player in neuroinflammation, has been confirmed in the pathogenesis of neurodegenerative diseases. This study is aimed to assess the effect of the interaction of cAMP-PKA and cyclooxygenase pathways on spatial memory acquisition in animal models. MATERIAL AND METHODS: In the present study, the effects of the four-day bilateral intra-hippocampal infusions of H-89 as a protein kinase AII inhibitor (10 µM/side), celecoxib (0.1 M/side) as a selective cyclooxygenase-2 inhibitor, cele-coxib/H-89 and bucladesine (10 µM/side)/celecoxib/H-89 on spatial memory acquisition in the Morris water maze were investigated. Control animals received bilateral intra-hippocampal infusions of dimethyl sulfoxide. Rats were trained for 4 days; each day included one block of four trials. Post-training probe trial tests were performed on day five. RESULTS: A bilateral intra-hippocampal infusion of H-89 and celecoxib led to a significant impairment in spatial learning compared to the controls through a notable decrease in escape latency and traveled distance. But, combination treatment of animals with celecoxib/H-89 and bucladesine/celecoxib/H-89 could considerably reverse celecoxib and H-89-induced spatial memory acquisition impairments in the Morris water maze. CONCLUSIONS: These results indicate the probable regulatory effects of cAMP/PKA and cyclooxygenase-2 signaling pathways on spatial memory acquisition in the Morris water maze.

Magnesium sulfate protects the heart against carbon monoxide-induced cardiotoxicity in rats.

Carbon monoxide (CO), a toxic gas produced via incomplete fossil fuel combustion, has several poisonous effects in the heart including induction of necrosis, apoptosis, and electrocardiogram (ECG) changes. Magnesium sulfate (MS) is a drug with cardioprotective effects especially when used after ischemia/reperfusion. In the current study, we aimed to evaluate MS cardioprotective effects following CO poisoning. Animals were exposed to CO 3000 ppm for 1 h and immediately after the exposure period and on the next 4 days (a total of 5 consecutive doses given on a daily basis), MS (75, 150 and 300 mg/kg) was injected intraperitoneally (i.p.) and ECG was recorded focusing on ST-segment, T-wave, and Q-pathologic wave changes. On day 5, animals were sacrificed and their heart was excised for determination of BAX, BCL2 and Akt expression level using western blot analysis and necrosis investigations. The results showed that MS significantly decreased necrosis and BAX/BCL2 ratio (P < 0.001) while pro-survival protein Akt was significantly increased (P < 0.001). Moreover, CO-induced ST-segment depression, T-wave inversion, and atrioventricular block (AV-block) were decreased following treatment with MS. In conclusion, our results showed that MS could decrease cardiac deleterious effects of CO poisoning including necrosis and apoptosis while increased the expression of Akt, as a cell survival protein.

Anticancer and apoptosis­inducing effects of quercetin in vitro and in vivo.

The present study focused on the elucidation of the putative anticancer potential of quercetin. The anticancer activity of quercetin at 10, 20, 40, 80 and 120 µM was assessed in vitro by MMT assay in 9 tumor cell lines (colon carcinoma CT­26 cells, prostate adenocarcinoma LNCaP cells, human prostate PC3 cells, pheocromocytoma PC12 cells, estrogen receptor­positive breast cancer MCF­7 cells, acute lymphoblastic leukemia MOLT­4 T­cells, human myeloma U266B1 cells, human lymphoid Raji cells and ovarian cancer CHO cells). Quercetin was found to induce the apoptosis of all the tested cancer cell lines at the utilized concentrations. Moreover, quercetin significantly induced the apoptosis of the CT­26, LNCaP, MOLT­4 and Raji cell lines, as compared to control group (P<0.001), as demonstrated by Annexin V/PI staining. In in vivo experiments, mice bearing MCF­7 and CT­26 tumors exhibited a significant reduction in tumor volume in the quercetin­treated group as compared to the control group (P<0.001). Taken together, quercetin, a naturally occurring compound, exhibits anticancer properties both in vivo and in vitro.

Neuro-Protective Effects of Resveratrol on Carbon Monoxide-Induced Toxicity in Male Rats.

Acute carbon monoxide (CO) poisoning causes neurotoxicity through induction of necrosis, apoptosis, lipid peroxidation and oxidative stress. Resveratrol (RES) is a natural polyphenolic phytoalexin that exhibits neuroprotective effects in ischemia/reperfusion due to its anti-apoptotic, anti-necrotic and strong anti-oxidant properties as well as its ability to activate pro-survival pathways. In this study, rats were exposed to CO 3000 ppm for 1 h. Immediately after poisoning and on the next four consecutive days, RES (1, 5 and 10 mg/kg) was administered intraperitoneally. On the fifth day, animals' brains were excised, and necrosis, lipid peroxidation level and the level of Akt, BAX and BCL2 expression were evaluated. The results showed that RES 10 mg/kg significantly reduced lipid peroxidation, but RES 1 and 5 mg/kg had no significant effect on this parameter. Furthermore, RES 5 and 10 mg/kg significantly increased Akt expression level, while BAX/BCL2 ratio was reduced by RES 1, 5 and 10 mg/kg. Moreover, RES reduced necrotic foci in the brain, but the best results were seen following treatment with RES 10 mg/kg. In summary, RES showed neuroprotective effect in CO-poisoned rats as it decreased necrosis and BAX/BCL2 ratio and increased Akt expression levels. Copyright © 2017 John Wiley & Sons, Ltd.

Effects of luteolin and luteolin-morphine co-administration on acute and chronic pain and sciatic nerve ligated-induced neuropathy in mice.

Background Neuropathic pain (NP) is a common condition accompanied by nerve injury. To date, there is no definite treatment approved for this disorder. In addition, many drugs that are used for NP cause adverse reactions. Luteolin is a naturally occurring flavonoid with diverse pharmacological properties such as anti-inflammatory, antioxidant and anticancer. We sought to investigate luteolin effects on chronic, acute and neuropathic pain as well as its potential to increase morphine anti-nociceptive effects in mice. Methods Albino mice (20-25 g) were randomly divided into 14 groups (n=7) including morphine 1 mg/kg body weight +luteolin (5 mg/kg body weight), morphine (9 mg/kg body weight, i.p.), luteolin (2.5, 5 and 10 mg/kg body weight), imipramine 40 mg/kg body weight and normal saline (NS) (0.9 %) as vehicle and subjected to hot plate test. Formalin test was done in the following groups: NS, diclofenac sodium (10 mg/kg body weight, i.p.), morphine (9 mg/kg body weight, i.p.) and luteolin (2.5, 5 and 10 mg/kg body weight). Results Administration of luteolin single dose (5 and 10 mg/kg body weight) significantly reduced neuropathic pain ( p<0.05$\rm{p}<0.05$) in comparison to negative control. Anti-nociceptive effects of luteolin were comparable to imipramine as the standard positive control ( p<0.001$\rm{p}<0.001$). Co-administration of luteolin and morphine potentiated morphine 1 mg/kg body weight painkilling effects ( p<0.001$\rm{p}<0.001$). Conclusions Our results showed that luteolin alone reduces neuropathic pain. Furthermore, when co-administered with morphine 1 mg/kg body weight, luteolin potentiates morphine effects. Therefore, luteolin-morphine co-administration might be a valuable alternative for the conventional treatment.

Effects of resveratrol on carbon monoxide-induced cardiotoxicity in rats.

Carbon monoxide (CO) poisoning leads to tissue hypoxia resulting in cardiovascular disturbances. Resveratrol (RES) is considered a natural cardioprotective agent especially in the setting of ischemia/reperfusion injury. In the present study, the cardioprotective potential of RES against CO-induced cardiotoxicity was evaluated. 45 male Wistar rats, animals were randomly assigned to 5 experimental groups. The first group served as negative control and was not exposed to CO. All remaining rats were exposed to CO 3000ppm for 60min. The second group received normal saline following CO exposure, while groups 3, 4 and 5 were injected intraperitoneally with different doses of RES (1, 5 and 10mg/kg, respectively). Histopathological examination showed that RES administration reduced myocardial lesions compared to control groups. Myocardial Akt expression was significantly increased in rats treated with the highest dose of RES (p<0.05) compared to CO-exposed non-treated animals. Caspase-3 activity in rat cardiomyocytes of RES-treated animals was significantly decreased in a dose-dependent manner. ECG findings did not differ significantly among CO-exposed groups. In conclusion, the present study offers evidence of a protective effect of RES administration on CO-induced cardiotoxicity via Akt up-regulation and attenuation of caspase-3 activity in rat hearts.

Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 µM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

Comparing Blood Lead Level among Oral/inhaled Opium Addicts with a Non-addict Control Group in the Southeast of Iran.

BACKGROUND: Opium is widely used among addicts in the Middle East countries such as Iran. Recent reports suggest that opium sellers cheat their customers by adding lead to the opium. Contaminated opium can threaten the health of consumers. This study was designed to evaluate the lead concentration in blood sample of oral and inhaled opium user's referring to Amir Al-Momenin Hospital in Zabol, Iran, during spring 2015 in comparison with those of control group. METHODS: Blood lead level (BLL) of 188 subjects with a mean age of 52.06 years in three categories - including oral opium addicted (55 patients), inhaled opium addicted (55 patients), and healthy control group (n = 78) - was assessed. The BLL of all the subjects was assessed using an atomic absorption spectrophotometer. FINDINGS: Almost all participants consumed "Tariak" (99.09%). Mean ± standard deviation (SD) duration of opium addiction was 13.21 ± 10.26 years. The average blood lead concentration among oral users, inhaled users, and control group were 34.31 ± 21.54, 41.13 ± 26.40, and 9.86 ± 4.40 µg/dl, respectively (P = 0.001). CONCLUSION: Our study showed significant differences of BLLs between opium users and control group. We also did not find any association between blood lead concentration and method of opium consumption.

Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice.

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.