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Background & Objective: It has been reported that, the ?-Carboline alkaloids of peganum harmala seeds have a stimulatory action on Serotonin and Catecholamines release in different brain regions. In addition, one of the most important pharmacological effects demonstrated for ?-Carboline is a revesible inhibitory action on MAO-A. These findings suggests that ?-Carboline, should alleviate at least some of the signs of depression. The purpose of present study is to determine the anti-depressant activity of ?-Carboline Harmane, Norharmane and Harmine. Materials & Methods: All experiments were carried out on male Swiss-Webster mice (25-30 g). The anti-depressant activities of the ?-Carboline were assessed using the forced swim test. This test is the most widely used tool for anti-depressant activity preclinically. In this test, mice were placed into a cylindrical glass (25 cm height, 12 cm in diameter) containing a column of 15 cm of water at 25±1°C. After 30 min of the ?-Carboline injections, the mice were subjected to forced swimming test for 8 min and their immobility time was recorded. Results: Interperitoneal (IP) injections of Harmane (5-15 mg/kg), Norharmane (2.5-10 mg/kg) and Harmine (5-15 mg/kg) significantly decreased the immobility time in the mouse forced swim test. The inhibitory effects of Harmane, Norharmane and Harmine were antagonized by Flumazenil (5 mg/kg, IP) but not by Reserpine (5 mg/kg, IP, 18 h before test). Conclusion: The results suggest that the anti-depressant activities of Harmane, Norharmane and Harmine may be mediated through an inverse agonistic mechanism.

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Background&Objective: Morphine is an opioid analgesic and has known effects on different organs. This study was done to determine the histopatological changes of liver due to morphine adminstration in adult mice. Materials&Methods: In this experimental study, 20 male Blab/c mice divided experiment and control groups. In experiment and control group, animals recived 15mg/kg/day morphine and salin normal interperitoneally, for 21 days respectively. Day 22 the livers were dissected under anaesthesiology. Specimens were processed for histological study and stanied with H&E. Results: In experimental group, small sites of necrosis with poly morphic inflammatory infiltration and debris formation of necrotized nucleus in death area, so hepatitis was suggested. Also accumulation of micro droplets of lipid inside the hepatocyte cytoplasm withont nucleus displacement (fatty damages with small vacuoles) observed in cases. In addition, microvesicular steatosis and mouth teeth necrosis in liver parenchyma with inflammation in the vein and portal space were seen in cases. Any changes was not seen in control group. Conclusion: The interperitoneal adminstration of morphine can cause histopatological changes in mice liver.

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Background & Objective: Bombesin (BBS) is a tetra-decapeptide amino acid neuropeptide in central nervous system within a variety of mammalian species. Also it has many biological effects that may be effective in modulation of anxiety. The aim of present study was to determine the effect of BBS on modulation anxiety reaction in elevated plus maze (EPM) in mice.

 

Materials & Methods: 60 male mice (25-30 g) were used in this study. Bombesin in doses of 1.25, 2.5, 5, 10 and 20 µg/kg IP or saline was injected in different groups 10 min before of evaluation. Five minutes later for increase of activity, animal was put in black box for 5 min. Then each animal in regulated time transferred to standard elevated plus-maze and the time spent in the open arms and the ratio of open arm entries during 5 min, were measured. The data analyzed by using ANOVA and Tukey test.

 

Results: BBS in dose dependently manner increase which the anxiety reaction in mice. Animals had spent lower time and ratio of open arm entries in compare with control group significantly (P<0.05) and BBS only in dose of 1.25 µg/kg did not showed significantly effect.

 

Conclusion: This study indicated that Bombesin in dose dependently manner have important role in modulate anxiety reaction in EPM in mice.

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Background & Objective: Many evidence indicated that action of glucocorticoid receptors can modulate anxiety behaviors and these effects probably mediated by nitric oxide (NO) system. Thus, in this study, we investigated interaction between corticosterone and NO on anxiety behaviors in mice in elevated plus maze (EPM).

Materials & Methods: In this experimental study male albino mice (25-30 g) were used. A standard EPM was used to determine anxiety behaviors. Two behavioral measures were used that include of the percentage of time spent in the open arms and the ratio of open arm entries to total entries during 5 min. Animals received IP injection of L-Name 30 mg/kg as an inhibitor or L-Arginine 50 mg/kg as a synthesis of NO or saline 60 min and corticosterone (1, 2.5, 5 mg/kg) 30 min before of evaluation.

Results: Analysis of data indicated that corticosterone at doses of 1 and 2.5, but not 5 mg/kg significantly reduced anxiety behavior in mice (P<0.05). Also pretreatment of L-Name potentiate but injection of L-Arginine had inhibition of corticosterone effects (P<0.05).

Conclusion: This study revealed that glucocorticoid induces anxiolytic effects and these effects probably potentiate by NO inhibitor and reduced by NO synthesis. Therefore, it seems that there are interaction between of glucocorticoid and NO system for control of anxiety behaviors.

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Background & Objective: Neural tube defects, growth retardation and nail hypoplasia are most common features of teratogenic effects of carbamazepine. This study was done to determine the effects of carbomazepine on eye development in Mice fetuses. Materials & Methods: In this experimental study 40 BALB/c pregnant Mice were divided into four groups. Experimental groups I and II received 15 mg/kg daily 6-15 GD (gestational days) and 30 mg/kg daily 6-15 GD intraperitoneal of carbamazepine, respectively. All drugs recolved in Tween20. Two control groups received normal saline or Tween 20. Dams were dissected on GD18 and embryos were collected. After observation of eye malformation in fetuses, we employed routine histological processes to stain the samples and also skeletal staining was performed. Results: Calvaria deformations, finger anomalies, brachygnathia and short tail in experimental groups I and II were 7% and 10.8%, 13.3% and 16.6%, 7.8% and 11.7%, 10.2% and 9.2% respectively. Ten of fetuses (8.6%) in experimental group I and nine of fetuses (7.5%) in the experimental group II had eye malformations. Premature opening of one or both eyes with mild to severe exophthalmos occurred in both of the experimental groups. Also, histological examination showed deformed lens, retinal folds with undeveloped layers, corneal fold with absence of surface epithelium. Conclusion: This study revealed that administration of carbamazepine during embryunic period can induce eye malformations in Mice fetuses.

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Background and Objective: Biological activity of hydrogen sulphide in smooth muscle of vessel and non-vessel tissue are contradictory. The aim of this study was to examine the effect of hydrogen sulphide on smooth activity of muscle mice jejunum. Materials and Methods: Experiments were performed on mice jejunum and motor activity was recorded from in vitro segments of jejunum ~ 4 cm in length. jejunal segments were mounted horizontally in separate perfusion chamber. Furthermore, using vanilloid receptor 1 deficient mice (VR 1-/-) we tested hypothesis that extrinsic sensory nerves mediated alterations, in motor activity responses in the presence different concentration of of hydrogen sulphide (100-3000 μM). Results: Serosal application of NaHS (as hydrogen sulphide donor) produced a dose-dependent inhibition of motor activity that are not significantly different between VR 1-/- and VR 1 +/+ mice. In the presence of TTX (1μM) NaHS (300µM) caused a reduction in basal tone (19.5%, p<0.05, n=5) and inhibited the contraction evoked by 30µM bethanechol by 55% (n=5, p<0.05). Conclusion: This study showed that hydrogen sulphide is an important motor activity inhibitor in mice jejunum.

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Background and Objective: The application of herbal extract are used as substitution to either drug or complementary medicine. Cinnamomum zeylanicum is one of the important herb which is used for various diseases. This study was done to determine the effects of Cinnamomum zeylanicum (Bark) hydroalcoholic extract on the level of hormones responsible for reproduction in male mice. Materials and Methods: In this experimental study, 48 male adult mice divided in six groups, hydroalcoholic extract of Cinnamon zeylanicum was injected intraperitonealy in different dose (50, 100, 200 and 400 mg/kg/every other day) for 20 days in groups 1-4. Normal saline was injected in only one group as placebo group and the other group was not given any substance and it was considered as a control group. All serum hormones level including FSH, LH and testosterone were measured by Radioimmunoassay (RIA) technique. Results: The concentration of FSH, LH increased following the injected dose of Cinnamon zeylanicum and the most increasing of FSH and LH concentration was in animals which receive 200, 400 mg/kg/every other day of Cinnamomum zeylanicum hydroalcoholic extract. The level of serum testosterone significantly increased in dose of 50, 100 mg/kg/every other day in comparison with control group, too (P<0.05). Conclusion: This study showed that hydroalcoholic extract of Cinnamon zeylanicum elevates the pituitary-gonadal axis hormones.

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Background and Objective: Carbamazepine (CBZ) is an antiepileptic drug that causes significant malformations such as neural tube defects (NTDs), cardiac, skeletal and craniofacial defects if it is consumed during pregnancy. The aim of this study was to evaluate the protective effect of folic acid on prevention of birth defect due to Carbamazepine in Balb/c mice. Materials and Methods: In this experimental study, Sixty Balb/c timed-pregnant mice were divided into 4 experimental and 2 control groups. Two experimental groups received daily intraperitoneal injections of 30 mg/kg (group I) and 60 mg/kg/body weight (group II) of CBZ on gestational days (GD) 6 to 15. Two other experimental groups (group III and IV) received similar doses of CBZ with folic acid supplement (3 mg/kg/day) by gavages route for 10 days before pregnancy and 15 days after GD0 (gestational day 0). Two control groups received normal saline or Tween 20 (polysorbate 20). Dams underwent cesarean section on GD18 and embryos were collected. External examination was done and data concerning malformations, weight and crown- rump of fetuses were collected and analyzed by using SPSS-11.5 software and ANOVA and chi-square tests. Results: The mean weight and crown-rump of the fetuses in both experimental groups I and II were significantly reduced. Also in both experimental groups I and II various malformations were detected such as open eyes, limb defects, scoliosis, facial deformity and NTDs. The mean weight and crown-rump of fetuses in the folic acid treated groups did not show any meaningful differences in comparison with fetuses in experimental groups I and II. Also, meaningful reductions in eye, vertebral, limb and facial defects were seen in fetuses of group III. In experimental group IV, reduction of vertebral and limb defects were observed. Conclusion: This study showed that consumption of folic acid (3 mg/kg/body weight) before and during pregnancy can reduce birth defects due to CBZ in Balb/c mice fetus.

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Background and Objective: The food additives, like sodium and potassium benzoate are used in many food products and drugs to prevent the growth of yeast and molds. There is no report about the histopathological effect of potassium benzoate. Placenta, has a critical role in embryonic development therefore this study was set up to evaluate the effects of potassium benzoate on placenta of BALB/c mice.

Materials and Methods: 45 BALB/c female mice were allocated into two experimental (1, 2) and one control groups. Experimental groups received daily intraperitoneal injection of 280 and 560 mg/kg/body weight of potassium benzoate and control group received normal saline. All injections were done during 10 days before mating and 5^th to 16^th of gestational days (GD). In GD 18 all placenta were removed via cesarean section. Macroscopic studies for morphological abnormalities were done and after measuring of placental weight and diameter, for microscopic studies the specimens were fixed and tissue passage were done. Tissue sections were stained with hematoxylin-eosin and histopathological changes were studied. Weight, diameter and percentage of agenesis of placenta in all groups were gathered. Data analyzed with using
SPSS-11.5, ANOVA and Tukey tests.

Results: The mean weight and diameter of the placenta in both experimental groups 1 and 2 were significantly decreased compared to control group. Also atrophy of placenta in the experimental groups was increased significantly compared to the control group (P<0.05). Comparison of weight and diameter between groups 1 and 2 was not significant. Percentage of placenta agenesis in the experimental groups was increased significantly compared to the control group (P<0.05). Massive hemorrhage in labyrinth zone, fetal and maternal zones were seen in both experimental groups.

Conclusion: This study showed that exposure of potassium benzoate during mice pregnancy cause morphological and histopathological changes of placenta, including decrease of weight and diameter, agenesis, hemorrhage and tissue disorders.

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Background and Objective: The pregnancy period is very sensitive and complicative stages of life. It has been shown that addictive drugs such as ecstasy (MDMA: Methylene Dioxy Metha Amphetamine) can interfere in this stage. The aim of this study was to assess the effect of Methylene Dioxy Metha Amphetamine administration during pregnancy on reproductive system of BALB/c mice. Materials and Methods: In this experimental study, 10 and 5 female BALB/c mice were randomly selected as cases and controls, respectively. The pregnancy was induced following ovarian hyperstimulation with PMSG and hCG followed by mating with male animals. MDMA (5 mg/kg) and saline was injected intraperitoneally in day 7 and 14 of pregnancy in experimental and controls, respectively. The ovarian structure, as well as uterine tube, uterine horns and body, and vagina were studied histologically using light microscopy 27 days post delivery date. Data analyzed by using SPSS-17 and Chi-Square and Fisher exact test. Results: The rate of primary follicles was decreased from 18.42% in experimental to 33.33% in controls (P<0.05). The rate of mature follicles was significantly increased in experimental mice as compared to controls (P<0.05). The number of atretic bodies was lower in experimental than controls. The cellular alterations were observed in some portions of uterine tubes and uterine horns after ecstasy administration. However, no alterations observed in other parts of reproductive system. Conclusion: This study showed that MDMA cause some structural alterations in the uterine tubes and uterine horns, increase follicular maturation and reduction of follicular atresia in BALB/c mice.

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Background and Objective: Electromagnetic waved generated by electronic industries and the increasing use of electrical appliances have led to higher rise in chronic exposure to extremely-low-frequency electromagnetic field (ELF-EMF). This study was done to investigate the effects of low electromagnetic field on mice embryos development. Materials and Methods: In this experimental study, eighty female NMRI mice were super ovulated and coupled with male mated over the night. Next morning the female mice with a vaginal plug were identified as pregnant mice. Animals allocated into 2 groups control group was not exposed to EMF and animals in case group exposed to 50 Hz and amp 1.2 mT EMF the pregnant mice were scarified by cervical dislocation at 24, 72, 81, 96, 110 and 120 hours. Embryos were subsequently obtained from the mice by flashing the fallopian tubule and uterus horn. Data were analyzed using SPSS-13.5, ANOVA and student’s t-tests. Results: The number of 2, 3-4 cells and 5-8 of embryo cells and blastocyst decreased in case group compared to controls, but these reduction were not significant. The number of morula in cases significantly reduced in comparison with control group (P<0.05). The average number of fragmented blastocyst in experimental groups siginficantly increased compared to control group (P<0.05). The number of inner cell mass and trophoectoderm in experimental group significantly reduced in comparison with controls (P<0.05). Conclusion: The exposure of extremely-low electromagnetic field in pregnancy reduces the number of morula, inner cell mass and trophoectoderm.

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Background and Objective: Carbamazepine during pregnancy can induce various malformations. Recent studies have showed an increase in homocysteine level due to Carbamazepine administration. This study was to evaluate the effect of Carbamazepine on homocysteine serum level in pregnant mice and fetal malformations outcome. Materials and Methods: In this experimental study, 40 BALB/c timed-pregnant mice were allocated into 2 experimental and 2 control groups. The experimental groups were received daily intraperitoneal injections of 30 mg/kg (group I) or 60 mg/kg (group II) of Carbamazepine on gestational days 6 to 15. The control groups were received either - normal saline or Tween 20. Dams underwent Cesarean section on GD 18. External examinations were done and all data concerning malformations, weight and crown-rump of fetuses collected. Blood samples were collected from Dams' hearts prior to performing the Cesarean section. Homocysteine was measured using ELISA method. Data were analyzed using SPSS-18, ANOVA, Chi-Square and Tukey tests. Results: Significant increase in Homocysteine levels of dams’ serum compared to control groups was seen in both experimental groups I and II (10.56±1.31 and 11.11±1.64 µmol/L, respectively, P<0.05). The mean weight and crown-rump of the fetuses in both experimental groups were significantly reduced compared with those of the control groups (P<0.05). Various malformations such as limb defects, vertebral defects, facial deformity and severe malformations were observed in fetuses of both experimental groups. Conclusion: Serum elevation of homocysteine in Carbamazepine exposed pregnant mice may be a risk factor for induction of fetal malformations.

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Background and Objective: Anxiety and depression are experienced following addicted patients durg withdrawal. This study was done to determine the effect of methadone and valproate combination on morphine withdrawal-induced anxiety and depression in male mice. Methods: In this experimental study, ninety-eight male mice were allocated into acute and chronic categories. Animals in acute chronic categories allocated into seven groups including: saline, morphine, methadone (10 mg/kg/bw), valproate (150 mg/kg/bw), three groups of valproate+methadone, in of ratio 1:1, 2:1 and 1:2. Animals were received escalating dose of morphine for 8 consecutive days except saline group. In chronic group, drugs were injected for 30 minutes before morphine administration, while in acute group the drugs were used only at day 8. Anxiety and depression due to naloxone injection (5 mg/kg/bw) was investigated by elevated plus-maze, tail-suspension and open field tests. Results: In the chronic group, valproate + methadone (2:1) combination therapy showed a significant increase in the percentage of open arm entries (53.86±1.9) and percentage of time spent in the open arm (58.58±4.15) compared to the morphine group, with a percentage of entering (28.12±2.03) and percentage of time (17.88±1.77) (P<0.05). In open field test, the ratio of the number to the duration of time spent in the central square, in the combination therapy groups of methadone+valproate (27±2), valproate+methadone (1:2) and valproate+methadone (2:1) were significantly increased in compare to the morphine group (P<0.05). In tail-suspension test, duration of immobility as an indicator of depression, in the treatment group of valproate+methadone (2:1) was significantly reduced (P<0.05). Conclusion: Valproate and methadone combination therapy particularly in ratio of 2:1 can reduce morphine withdrawal-induced anxiety and depression in animal model.

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Background and Objective: The blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system. In this study, the capability of biopartitioning micellar chromatography (BMC) using the mixed micellar system of Brij-35/sodium dodecyl sulfate (Brij-35/SDS, 85:15 mol/mol) has been studied to predict pharmacokinetic parameter (BBB penetration ability) of 14 basic drugs.

Methods: In this descriptive-analytical study, the potential of BMC using mixed micellar system (Brij-35/SDS, 85:15 mol/mol) in 0.04 M at physiological pH 7.4 was evaluated to predict pharmacokinetic parameter (BBB penetration ability) of 14 basic drugs. The regression model for the prediction of blood-brain distribution coefficient is derived from the multiple linear regression analysis using the training set in mixed micellar mobile phase. Also, the predictive ability of model was evaluated for a prediction set of 5 compounds (Chlorpromazine, Mianserin, Propranolol, Cimetidine, and Thioridazine). The fair R2 indicates good stability and predictive ability of the developed model for the drugs not included in modeling.

Results: The relationship between the BMC retention data of 14 basic drugs and their log BB parameter showed a good statistically model (R2=0.822, F=25.42, SE=0.225, R2CV=0.781).

Conclusion: This study points out the usefulness of mixed micellar solution of Brij-35/SDS, 85:15 (mol/mol) in BMC as a high-throughput primary screening tool that can provide key information about the blood-brain distribution of basic drugs in a simple and economical way.

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Background and Objective: Burn is one of the leading causes of mortality in the world. This study was done to determine the effect of the lavender, sesame oil, and combination of Lavender with sesame oil and silver sulfadiazine on the burn wound healing in mice.
Methods: In this experimental study, 30 male adult albino mice were randomly allocated into 5 groups as follows: the negative control group (physiology serum); the positive control group (silver sulfadiazine); the first experimental group (sesame oil), the second experimental group (combination of Lavender with sesame oil) and the third experimental group (Lavender oil).Second degree of  burn wound healing  take place using hot sheet with a diameter of 2 cm. wound treatment was done in five groups in 21-day treatment period. The wound diameter size and restoration percentage were measured on days 1, 3, 6, 9, 18, and 21. Some mice were euthanized and the samples of wounds were used for histopathological studies.
Results: The percentage of wound healing significantly increased in groups of silver sulfadiazine, combination of Lavender with sesame oil, Lavender oil and  sesame oil in compared to control group (P<0.05). The improvement percentage was seen in sulfadiazine and combination of Lavender with sesame oil groups in compared to negative control group. The level of tissue restoration based on the accumulation of collagen, fibroblasts, re-epithelialization were seen in sulfadiazine, combination of Lavender with sesame oil, Lavender oil and sesame oil, respectively.
Conclusion: Combination of Lavender with sesame oil similar to silver sulfadiazine has tissue restoration effect on burn wound healing in animal model.

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Background and Objective: Finding the pain relieving substances is one of the important aims of biological researches. This study was done to evaluate the antinociceptive, anti-inflammatory effects of Hyssopus officinalis extract in mice.
Methods: In this experimental study, 100 male adult mice were allocated into 5 experimental groups including control group receiving only normal saline and groups that received extract of Hyssopus officinalis at doses of 25, 50 and 75 mg/kg/bw, and positive control group in formalin test received morphine in acute and chronic phase of experiment and positive control group in anti-inflammatory test received dexamethasone. Formalin-induced paw licking was used to determine the anti-nociceptive activity of Hyssopus officinalis extract. The anti-inflammatory activity was determined by Xylene test.
Results: In the acute phase of pain (the first 5 minutes), doses of 50 and 75 mg/kg/bw (7.75±2.3, 8.75±2.1) of the Hyssopus officinalis extract significantly reduced the number of feet raised (P<0.05). Also, in the chronic phase of pain (20 min second), 25, 50 and 75 mg/kg/bw of doses (17.25±2.3, 11.75±2.9, 2.7±10.75) and morphine significantly reduced the duration of foot lift (P<0.05). The extract of Hyssopus officinalis with three doses of 25, 50 and 75 mg/kg/bw (13.33±3.1, 20±3.1, 19.83±2.8) showed high anti-inflammatory activity against Xylene induced ear edema (P<0.05).
Conclusion: This study showed that Hyssopus officinalis extract can inhibit pain and inflammation in animal model.

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Background and Objective: Due to the properties of herbal remedies and their lesser side effects than chemical drugs, much attention has now beeing paid to herbal treatments. The aim of this study was done to evaluate the antinociceptive and anti-inflammatory effects of hydroalcoholic extract of aerial parts of Ruscus aculeatus.
Methods: This experimental study was performed on 80 male NMRI mice (6-8 weeks) weighing 23-25 gr. Animals were randomly allocated into 5 groups including: control group (distilled water), positive control group (morphine 10 mg/kg/bw in pain test and dexamethasone 15 mg/kg/bw in inflammatory test) and three groups receiving 75, 150 and 300 mg/kg/bw Hydroalcoholic extract of Ruscus aculeatus L. The pain was evaluated by formalin test and an investigation of inflammation conducted by xylene induced ear-edema.
Results: The hydroalcoholic extract of Ruscus aculeatus L significantly reduced acute pain at 300 mg/kg/bw in compared to control group (P<0.05). Inhibition percent was 60% for acute pain and 85% in morphine group. Also, this plant caused significant reduction of formalin induced chronic pain at 150 and 300 mg/kg/bw doses in compared to the control group (P<0.05). At 150 and 300 mg/kg doses of Ruscus aculeatus L, inhibition of chronic pain was 71%, and 94%, respectively in compared with 97% inhibition in morphine group.
Conclusion: Hydroalcoholic extract of Ruscus aculeatus L at the dose of 300 mg/kg/bw reduces acute and chronic pain and at the dose of 150 mg/kg/bw reduces acute pain in laboratory animals.

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Background and Objective: Oxaliplatin is the main agent used in the treatment of colorectal cancers. Oxaliplatin inhibits DNA replication and transcription and to induce apoptosis or necrosis in cancer cells and rapidly dividing cell lines. This study was designed to determine the effect of Oxaliplatin on sperm parameters of 60 days old offspring during pre-pregnancy, pregnancy and lactation period in mice.
Methods: In this experimental study, 32 female NMRI mature mice were randomly allocated into 4 groups. Animals in control group were received 0.2 ml saline intraperitoneally (IP) during 21 days of pre-pregnany, pregnancy and lactation periods. Animals in experimental groups including pre-pregnant, pregnant and lactation groups were received 3 mg/kg oxaliplatin trice a week IP during 21 days before mating, during pregnancy and lactation periods, respectively. At the 60th postnatal day, all the male offspring were euthanized and sperm samples were obtained. Analysis of sperm parameters including count, motility, vitality, maturation and DNA integrity was done.
Results: Sperm count, motility and DNA integrity were significantly reduced in all three groups of Pre-pregnancy, pregnancy and lactation in comparison with control group (P<0.05). Moreover, the percentage of immature and dead sperms were significantly increased in oxaliplatin groups (P<0.05).
Conclusion: Admistration of oxaliplatin induces adverse effect on sperm quality in perinatal period. The greatest effect of this drug is on lactation period. Also, by increasing the time interval for oxaliplatin administration in mice to puberty of offspring, the adverse effects of this drug on the quality of sperm parameters are reduced.

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Background and Objective: Aspartame is a kind of artifical and non-sugar sweetener that is used as a sugar substitute in some foods and beverages. This study was done to determine effect of Aspartam on histomorphometric alterations, kidney function and expression of Bcl2, Bax, Caspase 3, P53 Genes in Mice.
Methods: In this experimental study, 36 adult male NMRI mice were allocated into four groups including control group and three experimental groups. The mice in the control group received 0.3 ml of distilled water by oral gavage for 90 days and the experimental groups received 40, 80 and 160 mg/kg aspartame, respectively orally and daily. One day after treatment, blood and kidney tissue samples were taken to evaluate biochemical, histomorphometric alterations and gene expression.
Results: Renal capsule diameter, glomerulus diameter and height of the epithelial layer of distal and proximal tubules were significantly reduced in treated groups compared to control group with increasing dosage of aspartame (P<0.05). However, the size of the urinary space and the diameter of the lumen of distal and proximal tubules were significantly increased in treated groups in compared to control group (P<0.05). The level of blood nitrogen urea (BUN) and creatinine significantly increased treated groups in compared to the control group with increasing dosage of aspartame (P<0.05). Also, with increasing dosage of aspartame, Bcl2 gene expression significantly reduced in treated groups in compared to the control group (P<0.05) however expression of Bax, Caspase 3 and p53 genes were significantly increased in treated groups compared to the control group (P<0.05).
Conclusion: Aspartame can cause changes in biochemical, histomorphometric indices, expression of Bcl2, Bax, Caspase 3 and P53 genes in mice kidney.

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Background and Objective: Spirulina (Spirulina platensis) has numerous nutritional and therapeutic benefits. This experimental study aimed to investigate the effect of spirulina on changes in the levels of liver enzymes of male BALB/c mice exposed to a high dose of acetaminophen.
Methods: In this experimental study, 42 adult male BALB/c mice were divided into seven groups of six. The toxic dose of acetaminophen 600 mg/kg body weight was considered. The control group received only a standard diet and water. The sham group was gavaged with saline solution. The third to seventh groups were treated as: acetaminophen; spirulina 600 mg/kg/bw, spirulina 300 mg/kg/bw, spirulina 600 mg/kg/bw + acetaminophen, and spirulina 300 mg/kg/bw + acetaminophen, respectively. In all groups, mice were treated with acetaminophen and spirulina powder by gavage for 14 consecutive days. Twenty-four hours after receiving the last dose of medication and deprivation of food (the animals still had access to water), the animals were anesthetized and blood samples were taken from the heart. Activity of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) was measured by spectrophotometry. Protein concentration was determined by the Lowry method. Catalase activity was assessed using hydrogen peroxide. The amount of malondialdehyde was measured and the total antioxidant capacity was determined by FRAP method by reducing ferric to ferro ions.
Results: The levels of serum transaminases (ALT, AST, ALP) as well as the level of total antioxidant capacity and malondialdehyde of the acetaminophen-treated group increased significantly compared to the control group (P<0.05). The levels of these enzymes in the group treated with S. platensis 300 mg/kg/bw + acetaminophen decreased significantly compared to the group treated with acetaminophen (P<0.05). Catalase activity in the acetaminophen group was significantly decreased compared to the control group (P<0.05).In the group of S. platensis 300 mg/kg/bw + acetaminophen, catalase activity increased significantly compared to the acetaminophen group (P<0.05). The results of experiments in two groups of spirulina and acetaminophen showed that the active ingredients of the algae at a dose of 300 worked better than 600 mg per kg of body weight in response to oxidative stress.
Conclusion: Consuming 300 mg/kg of S. platensis along with a near toxic dose of acetaminophen increases resistance to oxidative stress and injuries caused by drug poisoning by affecting the activity of enzymes and the antioxidant defense system.