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Background and Objective: Atorvastatin is a member of the statin family with lipophilic character and anti-hyperlipidemic effect. There is many evidence that atorvastatin has protective effect on cognitive function. This study was done to evaluate the effect of atorvastatin on spatial memory in rats following a high-fat diet.
Methods: This experimental study was performed on 35 male Wistar male rats. Animals were randomly allocated into 5 groups including control, control plus atorvastatin and sham (received high-fat diet for 4 weeks) and high-fat diet plus atorvastatin (10 and 50 mg/kg, for 4 weeks). Learning and spatial memory were measured using Morris water maze for a 6-day period including 5 days training and the last day, test day (probe day).
Results: High-fat diet reduced learning and poor memory performance during training and probe compared to the control group, and also on the probe day, the high-fat group spent less time in the target quarter (P<0.05). Administration of atorvastatin after a high-fat diet improvement spatial memory in compared to high-fat group (P<0.05).
Conclusion: Short-term treatment (4 weeks) with atorvastatin in high-fat dietary rats can improve spatial memory.

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Background and Objective: Hyperlipidemia and high level of serum total cholesterol are risk factors contributing to prevalence and severity of cardiovascular complications like coronary heart diseases. Lamiaceae plants have terpenoids and flavonoids can reduce triglyceride and cholesterol, therefore. This study was done to evaluate the effect of feeding with essential oil of Thymus deanensis Celak. on lipid profile, blood urea and liver enzymes in hyperchlostrolemic male Wistar rats.

Methods: This experimental study was performed on 36 male Wistar rats. Animals were randomly divided into 6 groups (there were 6 rats in each groups). The groups including control, sham, two groups receiving 200 and 500 ppm Thymus deanensis essential oil and hyperchlostrolemia groups treated with doses of 200 and 500 ppm of Thymus deanensis essential oil. Hyperchlostrolemia was induced by giving high cholesterol (2%) and sweet almond oil (97.5%) diet. The animals were treated for 32 days with essential oil of the thyme. At the end of the 32-day trial, blood sampling was performed. Total cholesterol, triglyceride, urea and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) liver enzymes were measured.

Results: The level of ALT and AST in hypercholesterolemia rats were significantly increased in comparison with the control group (P˂0.05). Thymus daenensis essential oil significantly reduced level of triglycerides and cholesterol (P˂0.05). The high dose of Thymus daenensis (500 ppm) essential oil more than a low dose (200 ppm) significantly reduced the level of cholesterol and triglyceride (P˂0.05). Blood urea nitrogen significantly increased in hypercholesterolemia group in compare to control group (P˂0.05). After the administration of essential oil with a minimum and maximum dose in hypercholesterolemia rats, the level of urea in the blood significantly decreased (P˂0.05). The level of ALT and AST in hypercholesterolemia rats significantly increased in comparison with the control group (P˂0.05). AST level significantly reduced in the groups of rats which received minimal and maximal doses compared to the group hypercholesterolemia (P˂0.05).

Conclusion: By lowering blood lipids, urea and liver enzymes after the use of essential oils, it seems that the Thymus daenensis dose-dependent is effective in improving liver function, kidney and high level of  lipid.

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Background and Objective: Diabetic mellitus nephropathy is one of the most important implication factors in kidney´s physiological function in diabetes mellitus. Having major role in filtration, in hyperglycemic condition kidney has shown more damages in comparison with other tissues. This study was done to determine the effect of combined Atorvastatin and Zinc oxide on the biochemical and histopathological alterations in kidney of diabetic rats.

Methods: In this experimental study, 40 female Wistar rats were randomly allocated into five groups including normal control (NC), diabetic control (DC), diabetic rats treated with atorvastatin (20mg/kg/bw daily, orally) (D+A), Zinc oxide (30mg/kg/bw daily, orally) (D+Z) and combination of each drug in half dose (daily, orally) (D+A+Z). Diabetes induced in rats by a single intraperitoneal injection of 60mg/kg/bw streptozotocin-diabetic.Animals treated for one month. At the end of the study, kidney weight and body weight and biochemical factors including creatinine and urea were measured to assess renal function. For determing the histopathology of kidney tissue, sections with 4-5 micrometer were stained with hematoxylin and eosin.

Results: The level of serum creatinine and urea was significantly increased in diabetic rats in compare to controls (P<0.05). Treatment of diabetic rats with half doses of combination of atorvastatin and Zinc oxide reduced the level of creatinine, urea and renal tissue damage in comparision with diabetic rats without treatment (P<0.05).

Conclusion: This study showed that the combination of atorvastatin and Zinc oxide has effect on controlling diabetic nephropathy.

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Background and Objective: Fenvalerate is a component of the pyrethroid pesticide induces oxidative stress. This study was done to determine the effect of garlic extract (GE) and N-acetylcysteine (NAC) against fenvalerate-induced oxidative stress in the serum and testis tissue of rat.

Methods: In this experimental study, 42 Wistar rats were randomly allocated into 7 groups including: control group, sham group (normal saline), the first experimental group receiving NAC (80 mg/kg/bw), the second experimental group receiving fenvalerate (10 mg/kg/bw), the third experimental group receiving fenvalerate (10 mg/kg/bw) + garlic extract (40 mg/kg/bw), the fourth experimental group receiving fenvalerate (10 mg/kg/bw) + NAC (80 mg/kg/bw) and the fifth experimental group receiving fenvalerate (10 mg/kg/bw) + garlic extract (40 mg/kg/bw) + NAC (80 mg/kg/bw). Injection of fenvalerate was performed intraperitoneally for 7 consecutive days in animals of intervention groups. Afterwards, for 10 consecutive days, NAC and garlic extract were injected. In this study, 1/40 LD50 fenvalerate was used. The activity of the catalase (CAT), glutathione S-transferase (GST), malondialdehyde (MDA) and total antioxidant capacity (TAC) were determined in serum and testis tissue in all animals.

Results: MDA level of serum and testis tissue in fenvalerate group increased significantly compared to the control group (P<0.05). The injection of NAC and garlic extract alone (P<0.05) as well as garlic extract in combination with NAC reduced MDA level of serum and testis tissue compared to fenvalerate group (P<0.05). Serum TAC level was significantly reduced in fenvalerate group compared to control (P<0.05). Serum TAC level was significantly increased in fenvalerate + GE group, fenvalerate + NAC group and fenvalerate + GE + NAC group compated to the fenvalerate group (P<0.05). GST activity of serum was significantly increased in fenvalerate group compared to control (P<0.05). GST activity of serum was significantly reduced in NAC, garlic extract and combination of NAC and garlic extact groups compared to fenvalerate group (P<0.05).

Conclusion: In this animal model study, low dose (10 mg/kg/bw) fenvalerate induces oxidative stress. Garlic extract and N-acetylcysteine (alone and in combination) improve injures caused by fenvalerate.

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Background and Objective: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic hepatic diseases which may be associated with cardiovascular disease. This study aimed to consider the effect of combined therapy with resveratrol supplementation and interval exercise training on heart cells apoptosis in rats with NAFLD using TUNEL assay.
Methods: This experimental study was done on 35 Wistar rats. Animals were randomly allocated into five groups including control (healthy) and four NAFLD groups, including patient, resveratrol, interval exercise, and resveratrol + interval exercise. A TUNEL assay kit was applied for the detection of apoptosis in heart tissue.
Results: The patient group had significantly higher percentage of heart apoptotic cells (24.38±0.69%) compared to the other groups (P<0.05), while the resveratrol + interval exercise (9.02±0.49%) and resveratrol (9.47±0.83%) groups showed significantly lower mean levels of heart apoptotic cells compared to the patient and interval exercise (P<0.05) groups. There was no significant difference in mean of apoptotic cells between resveratrol and resveratrol + interval exercise groups. The mean of apoptotic cells in interval exercise group was 11.39±0.28%.
Conclusion: Nonalcoholic fatty liver disease is considerably associated with heart cells apoptosis. Resveratrol supplementation especially combined with interval exercise significantly reduces apoptotic cells in heart tissue.

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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: Researches has shown that exercise and nutrition exercises can have a different effect on serum Brain Derived Neurotrophic Factor (BDNF( levels and resting blood pressure in young people. This study was done to determine the effect of a period of High Intensity Interval Training (HIIT) with omega-3 supplementation on the serum levels of BDNF and resting blood pressure in inactive male students.
Methods: In this clinical trail study, 32 non-athlete male students were randomly divided into control, supplements, training and training + supplement. Subjects in supplementary group were received daily (2000 mg) of omega-3 capsules. The training groups were also subjected to HIIT training for 6 weeks. The training + Supplemental group also included a combination of the same training program were associated with omega-3 supplementation. BDNF levels were measured by ELISA method 24 and 48 hours perior the exercise protocol and after the last training session. Blood pressure disturbances were also evaluated at the same time and before blood sampling according to the recommendations of the British Heart Association.
Results: The serum levels of BDNF in the group after 6 weeks in the training + supplementation group and the training group increased significantly compared to the pre-test values (P˂0.05). Also, a significant difference between-group training + supplementation group and training, supplementation and control groups were observed (P˂0.05). Systolic and diastolic blood pressures were significantly reduced in training + supplementary, training and supplementation groups compared to pretest values (P˂0.05). A significant reduction in systolic blood pressure in the training + supplementation group was observed compared to supplemental and control groups (P˂0.05).
Conclusion: HIIT combined with supplementation with omega-3 supplementation improved the BDNF serum level and reducing resting blood pressure in inactive male students.

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Background and Objective: Alzheimer is the most common form of dementia in elderly persons. Oxidative stress is one of the main pathological factors in Alzheimer’s disease. This study was done to investigate the effect of crosin on histological changes of hippocampus and memory impairment which induced by scopolamine in the male rats.
Methods: In this experimental study, 30 male rats were randomly allocated into 3 groups including: control, scopolamine and scopolamine with crosin treated groups. Scopolamine with dose of 3 mg/kg/bw for one week and crocin with dose of 30mg/kg for two weeks were administered, intraperitoneally. The learning and spatial memory parameters were evaluated by Morris water maze test. Then the animals were sacrificed and their hippocampi were removed immediately for histological evaluation.
Results: Scopolamine injection causes significantly increased the number of dark cells in CA1 region of hippocampus in compared to control group (P<0.05). Treatment with crocin decreased dark cells and increased light cells number in CA1 region of hippocampus (P<0.05). Also treatment with crocin decreased memory impairment that induced by scopolamine in rats (P<0.05).
Conclusion: It seems that treatment with crocin has protective effects against neuronal damage of CA1 region of hippocampus and memory impairment that induced by scopolamine.

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Background and Objective: Sperm dysfunction and damage in spermatogenesis are the most common causes of male infertility. Diazepam is also a painkiller for benzodiazepines that can be addictive for a long time. This study was done to determine the effect of Diazepam on testicular tissue parameters and spermatogenesis in Rats.
Methods: In this experimental study, 30 Wistar male rats with a 250-200 gram weight were randomly allocated into 5 groups. Experimental groups were received diazepam with doses of (2, 3, 4, 5 mg/kg/bw) for 14 days, intraperitonally. Serum physiology was injected in control group. The animals were anesthetized and the testes and epididymis ductus defran were removed for examination, sperm motility, and percentage of live sperm.
Results: Weight, large and small testicular diameter, percentage of live sperm and number of sperm moving forward were reduced with injection groups, at a dose of 3 mg / kg in all factors except the number of sperm moving forward in compared to the control group. In other groups, only testicular weight was significantly reduced at a dose of 2 mg/kg (P<0.05).
Conclusion: Diazepam can affect spermatogenesis process in rats.

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Background and Objective: Copper oxide nanoparticles, in addition to useful applications, may have adverse effects on the organisms.This study was done to determine the effect of copper oxide nanoparticles on liver toxicity, enzymes changes and liver histological structure of rats.
Methods: In this experimental study, 40 Wistar male rats were randomly allocated into 4 groups. During 10 days, five times (one day interval), 3 groups of rats were received 10, 20 and 30 mg/kg of copper oxide nanoparticles with a diameter of less than 50 nm and purity of 99% and a surface of 80 m²/g intraperitoneally, respectively. One group was considered as the control group. Activity of Lactate dehydrogenase (LDH), Alkaline phosphatase (ALP), Aspartate transaminase (AST) and Alanine aminotransferase (ALT) enzymes were tested in two stages (one day and 15 days after treatment). Also, liver tissue sections were prepared and stained with hematoxylin-eosin.
Results: No significant alterations of AST enzyme activity were not seen between different groups in two stages. The activity of ALT, ALP, and LDH enzymes in the first stage showed a significant increase in all treatment groups compared to control and returned to normal after 15 days. Rat's weight changes were not statistically significant between different groups. Histological studies revealed multiple tissue injuries in dose-dependent in treatment groups which included mild and severe hyperemia, hepatocytes degeneration, hyperplasia and inflammation.
Conclusion: Injection of low doses of copper oxide nanoparticles, after 15 days, although changes in enzyme activity return to normal, but significant disturbances observes in the structure of the liver tissue.

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Background and Objective: Cancer can spread to distant parts of the body through the lymphatic system or bloodstream. Angiogenesis is a fundamental step in the transition of tumors from a dormant state to a malignant. Some changes in cancerous cells can be improved and treated using herbal extracts. Salvia species in Iranian traditional medicine were used against various infections, inflammatory diseases.This study was done to evaluate the effect of aqueous extract of Salvia atropatana leaf on subcutaneous tumor model of CT26 colon carcinoma in Mice.
Methods: In this experimental study, for the induction of colon carcinoma, 26CT cells were injected into 18 BALB/c male Mice. Subcutaneous injection was done in the right side of the animal. When the size of the tumor was 50±350 mm3, 18 Mice were randomly allocated into 3 groups, including controls, aqueous extracts a breakdown of each dose 50 and 100 mg/kg/bw. The group containing the aqueous extracts of Salvia atropatana leaf was injected for 14 days, daily. To monitor the therapeutic effects, the parameters of the stopping rate in the growth of the tumor, the relative volume changes and the doubling of tumor volume were evaluated. After sacrificed the animals at the end the fourteenth day of the study, tumors were dissected for histological study.
Results: The volume of tumors and the mean density of the number of vessels was significantly reduced in treated group 1 (50 mg/kg/bw of aqueous extracts of Salvia atropatana leaf) and treated group 2 (100 mg/kg/bw of aqueous extracts of Salvia atropatana leaf) in compared to control group (P<0.05). Reduction in density of cells and vascular sections was significantly reduced in treated group 1 (50 mg/kg/bw of aqueous extracts of Salvia atropatana leaf) and treated group 2 (100 mg/kg/bw of aqueous extracts of Salvia atropatana leaf) in compared to control group (P<0.05).
Conclusion: Aqueous extracts of Salvia atropatana leaf has anti-angiogenesis activity and significant inhibitory effects on tumor growth in animal model.

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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: The liver is the main organ involved in the metabolism of various drugs and toxins. Thus, it is highly vulnerable to damage caused by drugs and toxins. Alpinia officinarum belongs to the Ginger family and has been used in traditional Iranian medicine for its therapeutic effects on the digestive system, including strengthening the function of the stomach and organs, improving digestion and reducing bloating. In addition, the plant has anti-hyperlipidemic, anti-inflammatory, antiviral, antibacterial, anticancer and antioxidant properties. This study investigated the hepatotoxic effects of Alpinia officinarum rhizomes aqueous extract in male Wistar rats.
Methods: This experimental study was performed on 35 male Wistar rats that were randomly allocated into 5 groups of 7. Four groups received 100, 200, 400 and 800 mg/kg of the extract for 28 days, while a group did not receive the extract (control group). Tissue sections (5 microns) were stained by hematoxylin and eosin at the pharmacology laboratory of Golestan University of Medical Sciences. The groups were examined for liver tissue pathology, and the level of liver enzymes including aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) was measured by Pars Azmoun ELISA kit.
Results: Administration of the aqueous extract of Alpinia officinarum rhizome for 28 days by gavage increased the level of AST, ALT and ALP in the serum of rats. Tissue damage was observed in most groups receiving the extract.
Conclusion: The results show that consumption of the aqueous extract of Alpinia officinarum rhizome at a dose of more than 100 mg/kg can cause liver damage and is lethal at a dose of 800 mg/kg.
 

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Background and Objective: Leptin is associated with metabolic disorders and promotes the development of liver steatosis to steatohepatitis. It selectively increases the secretion of Tumor-necrosis factor-α (TNF-a) in response to saturated fatty acid. The general purpose of this research was to determine the effects of eight weeks of continuous training and silymarin supplementation on the serum levels of TNF-α and leptin in Wistar rats with fatty liver disease.
Methods: In this experimental study, 40 male Wistar rats aged three weeks and weighting 159±3 grams were randomly divided into five groups: normal diet/saline, high-fat diet/saline (control), high-fat diet/supplemented, high-fat diet/exercise/saline, and high-fat diet/exercise/supplement. The rats were fed 10 grams per 100 grams of body weight (standard diet 13% fat and high-fat diet 41% fat) for eight weeks, and silymarin (140 mg per kilogram body weight) were given by gavage for 2 weeks. The continuous aerobic exercise protocol consisted 30 minutes of treadmill running at 70-75% of VO₂max for eight weeks, five days a week. After sacrificing the animals, samples were taken and sent to the laboratory for histological analysis. The expression of leptin and TNF-α in the liver was measured using commercial ELISA kits.
Results: The findings showed a greater decrease in hepatic leptin concentration in the high-fat diet + continuous exercise + supplement group (P<0.05) compared to the high-fat diet + continuous exercise + saline group (P<0.05). Tukey's post hoc test showed a greater decrease in the concentration of hepatic TNF-α in the high-fat diet + saline group (compared to the high-fat diet + supplement group) (P<0.05), and the high-fat + exercise + saline group (P<0.05). The weight of the rats in the normal diet + saline group differed significantly from other groups (P<0.05).
Conclusion: The results indicated that the combination of continuous training with silymarin supplementation can help reduce leptin and TNF-α in rats with a high-fat diet, an effect not observed by silymarin supplementation alone. Therefore, the combination of continuous aerobic exercises and silymarin supplementation can further oxidize fat and reduce inflammation in the body.
 

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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.
 

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Background and Objective: Vincristine is an important anticancer drug, which is highly toxic to the liver. It is a naturally occurring polyphenol found in many plants. Some studies have shown the anti-inflammatory and antioxidant effects of resveratrol. This study was conducted to determine the hepatoprotective and antioxidant effects of resveratrol against vincristine-induced toxicity in mice.
Methods: In this experimental study, 32 female NMRI mice weighing 25-30 grams were randomly divided into four groups (n=8): control, vincristine, vincristine + resveratrol, and resveratrol. The animals received vincristine intraperitoneally at a dose of 3 mg/kg/bw once a week for four weeks. They also received resveratrol at a dose of 30 mg/kg for 28 days through gastric gavage. At the end of the study, the activity of alanine transaminase (ALT) and aspartate transaminase (AST) were measured. The level of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX), malondialdehyde (MDA) as well as total antioxidant capacity (TAC) was measured in the liver tissue of mice.
Results: The activities of ALT, AST, SOD, and GPX decreased in the vincristine group compared to the control group, while MDA level increased significantly (P˂0.05). Treatment with resveratrol in the vincristine + resveratrol group improved the evaluated parameters compared to the vincristine group (P˂0.05).
Conclusion: Resveratrol has protective and antioxidant effects against vincristine-induced oxidative damage in the liver of mice.
 

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Background and Objective: The application of different nanoparticles using green synthesis is increasing due to fewer complications. This study was conducted to identify the effect of cobalt ferrite nanoparticles synthesized with sumac extract on changes in biochemical and histological factors in rats.
Methods: In this experimental study, 30 five-month-old male Wistar rats with an approximate weight of 250-300 mg/kg of body weight were divided into three groups: The control group (saline receiving), the experimental groups receiving intraperitoneal cobalt ferrite nanoparticles synthesized with sumac extract at a dose of 10 and 20 mg/kg of body weight. Serum and tissue samples (liver, kidney, and spleen) were isolated. Serum concentrations of urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were determined. The photometric method was used to measure liver enzymes, the calorimetric method without omitting proteins based on the Jaffe method was used to measure creatinine, and the urease-glutamate dehydrogenase (GLDH) method was used to measure urea. Tissue samples were assessed by hematoxylin-eosin staining. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) microscopic studies were used for microscopic investigations.
Results: No statistical significance was observed in blood samples and factors (urea, creatinine, ALT, and AST) in the experimental groups compared to the control group. Similarly, in the morphological investigation, the size of the liver, kidney, and spleen of the groups receiving cobalt ferrite nanoparticles synthesized with sumac extract was normal compared to the control group.
Conclusion: Cobalt ferrite nanoparticles synthesized with sumac had no toxic effect on the rats’ liver, spleen, and kidney tissues.

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Background and Objective: Sodium valproate (SV) is a commonly used antiepileptic drug; however, its therapeutic application is limited due to its potential to induce oxidative stress. Resveratrol, a natural polyphenol, possesses antioxidant properties. This study was conducted to determine the effect of resveratrol on SV-induced oxidative stress in the hippocampal tissue of BALB/c mouse fetal brains.
Methods: In this experimental study, 40 pregnant female BALB/c mice were randomly assigned to 5 groups of 8, including control, SV at 40 mg/kg/bw, SV at 40 mg/kg/bw + resveratrol at 0.6 mg/kg/bw, SV at 40 mg/kg/bw + resveratrol at 0.35 mg/kg bw, and SV at 40 mg/kg/bw + resveratrol at 0.225 mg/kg/bw. SV was administered orally per day, and resveratrol was administered daily via intraperitoneal injection. From gestational day 8 to 18, pharmacological interventions were initiated and continued until the birth of the neonates. On gestational day 18, the maternal mice were anesthetized, and 8 fetuses from each group were separated. Following the anesthesia of the fetuses, the brain tissue was dissected. Subsequently, oxidative stress parameters, including the malondialdehyde (MDA) level in nmol/mg as an index of lipid peroxidation, glutathione (GSH) level alterations in µg/mg, and protein carbonyl (PC) level alterations in nmol/mg, were evaluated in the hippocampal tissue.
Results: SV induced oxidative stress by increasing MDA (4.8 nmol/mg) and PC (51.4 nmol/mg protein), and also decreasing GSH (31.86 μg/mg) in the brain tissue compared to the control group (P<0.05). In a concentration-dependent manner, resveratrol reduced oxidative stress by decreasing MDA and PC to 3.02 and 37.21 nmol/mg, respectively, and also by increasing GSH to 49.76 μg/mg in the brain tissue. The most significant effect was observed at a concentration of 0.6 mg/kg/bw, which was statistically significant compared to the SV group (P<0.05).
Conclusion: The combined administration of SV and resveratrol culminates in a reduction in inflammation and oxidative stress-related factors in mouse fetuses.
 

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Background and Objective: Ketamine, a derivative of phencyclidine, is utilized as an anesthetic agent in surgical procedures. Like other medications, it can be associated with various adverse effects on different organs in the body. This study was conducted to determine the effect of injectable ketamine on the histopathological changes in the liver in neonates born to pregnant rats subjected to short-term and long-term anesthesia.
Methods: In this experimental study, 15 pregnant female Wistar rats were randomly divided into 3 groups of 5 each: A control group, a short-term anesthesia group (receiving an intraperitoneal injection of ketamine at a dosage of 25 mg/kg/bw), three times per week for 4 weeks), and a long-term anesthesia group (receiving an intraperitoneal injection of ketamine at a dosage of 75 mg/kg/bw, once per week for 4 weeks). Following parturition and during the lactation period, when the neonatal rats reached two weeks of age, they were initially anesthetized and sacrificed for tissue sampling via intraperitoneal injection of 7 units of ketamine and 3 units of xylazine. Tissue samples, with a thickness of 5 to 6 microns, were sectioned and examined using light microscope after fixation in formalin.
Results: In the short-term anesthesia group, dilation of the centrilobular veins and fluid accumulation were observed, with an intensity score of 2. Additionally, some hepatocytes exhibited degenerative-necrotic changes, characterized by acidophilic and dark cytoplasm, with an intensity score of 1. In the long-term anesthesia group, the liver tissue showed hyperemic changes in the portal space with a score of 1, as well as increased dilation of sinusoidal spaces and centrilobular veins of varying sizes and irregularities, also with an intensity score of 1. Fluid and blood accumulation were also noted in some of these structures. In the control group, cellular structures were maintained with complete regularity, and the intensity score of changes was determined to be zero.
Conclusion: Ketamine administration to pregnant rats can induce histopathological changes in the liver tissue of their offspring. These detrimental changes were more pronounced in the long-term group compared to both the short-term and control group.

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Background and Objective: Stroke is considered one of the leading causes of mortality and disability worldwide. Excitotoxicity, neuroinflammation, and oxidative/nitrosative stress resulting from cerebral ischemia/reperfusion lead to cell death, cerebral edema, and cognitive-behavioral impairments, such as deficits in short-term and long-term memory. This study was conducted to determine the effect of minocycline on behavioral-cognitive impairments induced by global cerebral ischemia.
Methods: This experimental study was conducted on 56 male Wistar rats (weighing 220–280 g) at Ferdowsi University of Mashhad, Iran. The animals were randomly assigned to the following groups: Control, solvent, surgery, surgery + solvent + ischemia/reperfusion, surgery + ischemia/reperfusion, and minocycline-treated groups (administered intraperitoneally at doses of 11.25, 22.50, and 45 mg/kg/bw). At specified intervals following the surgical induction of global cerebral ischemia/reperfusion, a surgery procedure and a carotid artery occlusion method were employed for 20 minutes. Following a 30-minute interval post-procedure, the drug or solvent was injected intraperitoneally on day 0. These injections continued for seven consecutive days at a fixed time each day. On day 7, anxiety-like behavior was assessed using the open-field test. Subsequently, the Y-maze test was utilized to evaluate short-term memory, while the Morris water maze (MWM) test was employed to assess spatial long-term memory and reversal memory in the following days.
Results: In the Y-maze test, ischemia culminated in a 33% decrease in short-term memory performance (P<0.05). Minocycline at doses of 22.50 and 45 mg/kg/bw improved short-term memory by 20% and 25% compared to the ischemia group, respectively (P<0.05). In the open-field test, ischemia caused a 66% decrease in time spent in the center of the field, indicating increased anxiety (P<0.05). Minocycline at a dose of 45 mg/kg/bw reduced anxiety by 32% compared to the ischemia group (P<0.05). In the MWM test, ischemia significantly increased the time to find the platform on days 2 and 4 (P<0.05). Minocycline at doses of 22.50 and 45 mg/kg/bw significantly decreased the time to find the platform (P<0.05). In the reversal phase of the MWM test, ischemia led to a decline in long-term memory performance (P<0.05), while minocycline at doses of 11.25, 22.50, and 45 mg/kg/bw significantly improved performance (P<0.05). In the probe trials, ischemia reduced the time spent in the target quadrant by 54% in probe 1 and 47% in probe 2 (P<0.05). Minocycline at 45 mg/kg/bw increased the time spent in the target quadrant by 45% in probe 1 and 34% in probe 2 (P<0.05). No statistically significant changes in motor activity were observed between the groups.
Conclusion: Minocycline, particularly at doses of 22.50 and 45 mg/kg, significantly improves cognitive function, memory, and anxiety without inducing motor activity impairments following cerebral ischemia.