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Background: Sperm chromatin abnormalities are defects in nuclear maturation and DNA integrity. These defectsoriginated from defective spermatogenesis due to a lack of DNA repair during chromatin remodeling. Changes insemen elements can cause damage to chromatin. There is little information about the relationship between changesin trace metal elements and total antioxidant capacity (TAC) with sperm chromatin damage. The present study wasconducted to determine the relationship between Selenium (Se), Iron (Fe), Zinc (Zn), Copper (Cu) and the TAC ofsemen with the status of human sperm chromatin.Materials and Methods: In this experimental study, semen samples (n=30) were collected from healthy men referredto Kermanshah Motazadi Hospital and stored in liquid nitrogen; after thawing and centrifugation, sperm were separated.The atomic absorption method was used to measure the concentration of metal elements. The TAC was evaluatedusing the ferric-reducing antioxidant capacity of the plasma method. Furthermore, the integrity of sperm chromatinwas measured using the sperm DNA fragmentation (SDF) method.Results: The status of sperm chromatin had a non-significant correlation with body mass index (BMI, P=0.25, r=0.21)and a non-significant negative correlation with sperm count (P=0.71, r=-0.71) and motility (P=0.75, r=0.61). In addition,there was no significant relationship between sperm chromatin and the TAC of semen (P=0.92, r=0.01). Additionally,there was no significant correlation between Se, Zn, or Cu concentration (P>0.05) and Fe concentration,which had a partially positive relationship with the chromatin state of sperm (P=0.24, r=0.20).Conclusion: The trace metal elements in the seminal fluid did not play a significant role in the status of sperm chromatin.

Background: Despite modern developments in its management, still major concerns remain about drug resistance in chemotherapy. Natural adjuvants combined with chemotherapy might be the answer. We examined the anti-cancer, anti-proliferative and synergistic effects of Sambucus nigra extract with cisplatin chemotherapy (CDDP) on MCF-7 and MDA-MB-231 human cancer cell lines. Methods: MCF-7 and MDA-MB-231 cell lines were cultured in DMEM culture media, containing 10% FBS and 100 U/ml penicillin/streptomycin. The anti-proliferative activity of SNA, CDDP and their synergic doses were determined using MTT method. Next, the apoptotic, metabolic, and cellular resistance gene expressions were measured through real-time quantitative PCR technique. To show the apoptosis effects and to diagnose cellular damages, an annexin V/propidium iodide (AV/PI) kit and malondialdehyde level were performed, respectively. Results: The synergic doses of SNA and CDDP in MCF-7 were 1.25µM CDDP+1.25µM SNA and on MDA-MB-231 was 2.5µM CDDP+2.5µM SNA. The results of real-time PCR showed that SNA induced apoptosis, disrupted metabolic pathways and reduced cellular drug resistance. In addition, the combination of SNA with CDDP compared with CDDP alone was able to change the expression of these genes and increase the rate of MDA and apoptosis generation (P

Objective: Royal jelly (RJ) is a honey bee product for which, anti-inflammatory properties were shown in vitro. Nanoparticles, including nano-silver (NS), are plausible inflammation inducers that act by activation of immune cells and consequent production of pro-inflammatory cytokines. This project aimed to explore immunomodulatory effects of royal jelly and nano-silver on the kidney and liver. Materials and Methods: In this project, 40 male rats were grouped as follows: 10 rats as controls, 10 rats treated with RJ; 10 rats treated with both NS and RJ and 10 rats treated with NS. Liver and kidney interleukin (IL)-1β, -2, -6, and -33 levels were determined using commercial ELISA kits. Results: RJ reduced kidney IL-6 levels in comparison to control and NS--RJ groups. RJ and NS reduced kidney and liver IL-1β levels. Kidney IL-33 levels were decreased in the RJ and nano-silver groups in comparison to the NS--RJ group. Conclusion: Based on this study, it may be concluded that RJ together with NS can play anti-inflammatory roles and may affect the function of immune cells.

Quercetin is an herbal polyphenol with valuable antioxidant properties. Mercaptothion is categorized as organophosphates which can generate free radicals and induce male fertility disorders. This study was aimed to assess the impacts of Quercetin against destruction of male fertility parameters induced by Mercaptothion. 64 male rats were randomly assigned into 8 groups; control, and Mercaptothion (250 mg/kg) groups; Quercetin groups (7.5, 15, and 30 mg/kg) and Mercaptothion + Quercetin (7.5, 15, and 30 mg/kg). Treatments were administered intraperitoneally (Mercaptothion) and orally (Quercetin) daily for 65 days. The sperm parameters, testis malondialdehyde (MDA), total antioxidant capacity (TAC), testosterone level and height of germinal layer were evaluated. Expressions of p53, caspase-3, Bax, and Bcl-2 were measured through real-time quantitative PCR. Values of all factors were reduced significantly except the MDA level (which increased) in Mercaptothion group compared to the control group (p0.05). Quercetin reduced toxic effects of Mercaptothion on male fertility parameters.

Introduction: Busulfan drug for cancer treatment, due to the oxidation properties and free radicals production, causes disturbance on male fertility parameters, and leaves water spinach plant have antioxidant features. The current study was aimed to evaluate the effect of water spinach leaf on recovery of male genital injuries caused by Busulfan. Methods: This randomized controlled clinical trial was performed on 48 male rats of Wistar race in 2019. The specimens were divided into 8 groups including; normal saline, Busulfan, water spinach leaf extract with doses of 250, 500, and 1000 mg/kg, extract + Busulfan. Daily treatment for 2 months was administered intraperitoneally. Sperm parameters by colorimetric techniques and light microscopy, level of testis malondialdehyde by spectrophotometry, total antioxidant capacity and testosterone by ELISA method, and height of germinal layer through optical microscopy and Motic software were evaluated. Data analysis was applied by SPSS software (version 20) and Tukey post-hoc test. P< 0.05 were considered statistically significant. Results:The values of sperm parameters, testosterone hormone, and total antioxidant capacity were significantly decreased in negative control group than positive control (P < 0.01). Treatment by extract and extract + Busulfan in all doses significantly increased whole mentioned parameters compared to the negative control group (P < 0.01). In evaluated parameters in extract group alone, no significant changes were observed compared to the positive control group (P > 0.05). Conclusion: Leaf extract of water spinach plant increases the sperm quality and improves the Busulfan-induced adverse effects on male reproductive parameters.

Objective: Paclitaxel (PAC) is a chemotherapy drug and has an active role in the treatment of lung, breast, and ovarian cancers; however, its use causes increased levels of free radicals, leading to severe and irreversible organ damage. Thymus vulgaris is a species of flowering plant that contains various antioxidant chemical compounds. This study aimed to investigate the effect of T. vulgaris on PAC-induced oxidative damage in mice testis and sperm parameters. Methods: In this study, 40 BALB/c mice were divided into five groups: normal control (NC); positive control (20 mg/kg of PAC); and three treatment groups (4.5, 9, and 18 mg/kg doses of T. vulgaris extract + 20 mg/kg PAC). Treatments were administered intraperitoneally daily for 50 days. Finally, the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured using immunoassay method. Testicular stereological features and sperm parameters were also calculated. Antioxidant parameters were measured using nitrite oxide (NO) and perioxidation levels and ferric-reducing ability of plasma assay. The expressions of p53, caspase-3, Bax, and Bcl-2 were measured through real-time quantitative polymerase chain reaction. Results: T. vulgaris + PAC treatments at all doses significantly increased all parameters in NC and three treatment groups compared with the positive control group (20 mg/kg of PAC) (P < 0.05), except the LH, FSH, and NO levels, which were decreased. Further, significantly downregulated levels of p53, caspase-3, and Bax genes and? upregulated levels of Bcl-2 gene expression were noted in NC and three treatment groups in comparison with the positive control group (P < 0.05). Conclusions: T. vulgaris administration attenuates the toxic effects of PAC on male reproductive parameters.

Ipomoea aquatica (IA) with antioxidant properties is used in therapeutic trends. An organophosphate, dichlorvos (Dich), is a common insecticide with various side effects on living tissues. This study examines the role of IA on Dich-induced hepatotoxicity in male rats. Sixty-four male rats were divided into eight groups including sham, Dich (4 mg/kg/day, intraperitoneally), IA 1, 2, and 3 (250, 500, and 1000 mg/kg/day, respectively, orally), and Dich + IA 1, 2, and 3. All treatments were applied daily for 60 days. At the end of the treatment, the animals were sacrificed. The histopathological changes, leukocyte infiltration, and apoptosis were assessed by light and fluorescent microscopy. The serum levels of hepatic enzymes, nitrite oxide (NO), and total antioxidant capacity (TAC) were evaluated biochemically. Dich statistically significantly increased the NO level, hepatic enzyme activity, apoptosis, leukocyte infiltration, the mean diameter of hepatocytes (DHs), and central hepatic vein diameter (CHVD) and also decreased the TAC, mean weight of liver, and the total weight of rats compared to the sham group (P < 0.01). In all IA and Dich + IA groups, a statistically significant decrease was detected in apoptosis, leukocyte infiltration, hepatic enzyme activity, NO level, mean DH, and CHVD, whereas an increase in TAC level, mean liver weight, and total weight was detected compared to the Dich group (P < 0.01). IA, due to the antioxidant property, recovers the Dich-related catastrophic changes in liver.

Introduction: Morphine (MOR) as a psychoactive agent in the opium family causes free radicals accumulation which leads to failure in spermatogenesis. Gallic acid (GA), a polyphenolic acid, is found in various plants with antioxidant, anti-fungal, anti-viral, and anti-allergic activities. The purpose of this study was to evaluate the effects of GA against MOR-induced damage to the reproductive parameter of rats. Methods: Sixty-four male Wistar rats (8 weeks, 220-250 g) were categorized into 8 groups by random (n=8/each); normal control and MOR control groups; GA groups (5, 10, 20 mg/kg) and MOR + GA groups (5, 10, 20 mg/kg). Treatments were administered intraperitoneally (i.p), daily for 4 weeks. The sperm parameters, spermatogenesis index (SI), total antioxidant capacity, testosterone level, and seminiferous tube diameter (STD) were assessed. Results: All sperm parameters reduced significantly in the MOR control group than to the normal control group (P < 0.01). All parameters were significantly improved in GA and GA + MOR treatment groups compared to the MOR control group (P < 0.01). Conclusion: MOR caused a detrimental effect on male reproductive parameters. Also, no significant modifications were observed in all doses of GA treatments in comparison with the normal control group. GA compensates the toxic effect of MOR on reproductive parameters. Hence, GA administration is beneficial in MOR users.

Introduction: Methotrexate (Met) as a chemotherapy drug has many side effects, such as infiltration of neutrophils and the development of oxidative stress. Crocin (Cro), a carotenoid isolated from saffron, has numerous therapeutic characteristics including anticancer and antioxidant activities. This study was designed to evaluate the effects of Cro against hepatic damage in rats induced by Met. Methods: In this study, 48 male Wistar rats were randomly assigned into 8 groups, control normal (saline), Met control-treated group (20 mg/kg), Cro groups (12.5, 25, 50 mg/kg) and Met + Cro treated groups (12.5, 25, 50 mg/kg). Treatments were administered by intraperitoneal injection daily for 28 days. Griess technique was hired for the determination of serum nitrite oxide (NO) level. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were determined in order to assess liver function disturbances. In addition, Thiobarbituric acid reactive species, antioxidant capacity, the diameter of hepatocytes and central hepatic vein (CHV) were investigated. Results: Met administration significantly increased the liver malondialdehyde (MDA) and NO level, the mean diameter of CHV, hepatocytes and hepatic enzymes. Met also decreased the tissue FRAP level compared to the normal control group (P < 0.01). The Cro and Cro + Met treatments in all doses significantly reduced the mean diameter of hepatocytes and CHV, hepatic enzymes, hepatic MDA and NO levels and increased the tissue FRAP level compared to the Met control group (P < 0.01). Conclusion: It seems that the Cro administration improves liver injury induced by Met in rats.

Background: The application of methotrexate (MTX) as a chemotherapy agent and immune system suppressant has various side effects. Crocin, a xanthine derivative plant, has many therapeutic benefits. This study was planned to assess the effect of crocin on renal toxicity of MTX in a rat model. Methods: Forty eight rats were divided randomly into eight groups (n = 6), which received normal saline, MTX, crocin, and MTX + crocin for 28 days intraperitoneally. The levels of oxidative stress in kidney and blood serum were measured, and the kidney was analyzed histologically. Results: MTX caused an enhancement in the levels of thiobarbituric acid reactive substances and biochemical marker (creatinine and BUN). Besides, a significant decrease was observed in tissue parameters and antioxidant capacity compared to the normal control group (p < 0.001). The crocin and crocin + MTX decreased the biochemical markers, the levels of thiobarbituric acid reactive species, and tissue parameters considerably at entire dose (12.5, 25, and 50 mg/kg) and enhanced the antioxidant capacity levels compared to the MTX group (p < 0.001). Conclusion: Administration of crocin improves the damage caused by MTX in rats. The crocin by the establishment of balance in the levels of antioxidant prevents the damage to the renal cell membrane, and subsequently the renal damage repairs.

Background: Pentoxifylline (PEN) is a xanthine derivative with different functional characteristics including dilution of blood and increase in tissue oxygenation rate. Nitrosamines (NITs) are well known as strong carcinogenic agents. This study attempts to show the histopathological and biochemical effects of PEN against hepatotoxicity induced by NIT in rats. Methods: Sixty-four rats were assigned to eight groups including the groups of sham: NIT (40 mg/kg); PEN (25, 50, and 100 mg/kg); and NIT + PEN. Experimental treatments were applied either intraperitoneally (for NIT) or orally (for PEN) daily for 4 weeks. The relative expression level of p53 and Bax genes and hepatocyte apoptotic index were analyzed. Liver malondialdehyde (MDA), tissue ferric-reducing ability of plasma (FRAP), the diameters of hepatocytes (DH) and central hepatic vein (CHV), and biochemical liver function indicators (LFI) were investigated. Griess technique was hired for the determination of the level of serum nitrite oxide (NO). Results and Conclusions: NIT significantly increased the level of apoptotic gens and index, MDA, NO, diameter of CHV and DH, and LFI and decreased the FRAP level compared to the sham group (P < 0.01). All parameters in PEN and PEN + NIT groups significantly reduced (except FRAP level, which was decreased) in compared to the NIT group (P < 0.01) . By summarizing the results of this research, it is concluded that the PEN administration alleviates the hepatotoxicity due to oxidative stress produced by NIT in rats.

Background: As a major tumor suppressor gene, P53 plays a principal role in the apoptosis of cancer cells. Harmine is a harmal-derived alkaloid with antioxidant and anticancer properties. This study was designed to assess the ability of harmine to express P53 gene and stimulate apoptosis in breast cancer cell line. Methods: MCF-7 cell line was cultured and treated with harmine. Half maximal inhibitory concentration (IC50) assay was carried out through MMT method following 24 h of treatment. Flow cytometry technique was employed to measure apoptotic cells and real-time PCR was performed to estimate P53 gene expression in tumor cells. Results: The IC50 for the harmine extract in MCF-7 cells was 30 μM. Harmine administration in all treated groups resulted in a significant increase in apoptosis and P53 gene expression in MCF-7 cells (P < 0.00001). Conclusions: It seems that harmine administration is able to induce apoptosis in MCF-7 cells through the up-regulation of P53 expression.

Background: The study aimed to assess the effect of anti-tumor and anti-proliferative properties of Sambucus nigra (SNA) on MCF-7 and MDA MB-231 breast tumor cell lines. Methods: The cytotoxicity of SNA was assessed based on dose/time by the MTT assay. Also, the influence of SNA on apoptotic pathways, cellular and metabolic resistance in these cell lines was examined by real-time PCR, lipid peroxidase was measured by malondialdehyde (MDA) and the effect of apoptosis and necrosis was determined by flow cytometry. Results: Our data showed that DOX, SNA, and DOX + SNA treatment induced the expression of p53, Bax, Bcl-2, Caspase-3, and 8 levels involved in the apoptotic pathways. ATP binding cassette subfamily B member 4 (ABCB4) gene expression was decreased in MDA‑MB-231 breast cancer cells compared to MCF-7. Also, we observed that DOX, SNA, and DOX + SNA treatment induced expression of Monocarboxylate transporters (MCTs) metabolic pathways such as MCT1 and MCT4. Conclusion: Overall, the outcomes of this investigation show that the combination of SNA-Doxorubicin (DOX) in different groups of these cancer cells, especially in the MDA‑MB-231 cell lines synergistically intensified the induction of apoptosis in them. SNA enhances the anti-cancer effects of DOX to induce cellular apoptosis, alter metabolic pathways, and reduce cellular resistance. The research highlights the promising use of SNA as a chemosensitizer in the chemotherapy.

Background Nitrosamines as a carcinogenic agent has unfavorable effects on some of the male reproductive parameters. Pentoxifylline (PX) is a xanthine derivative used as a drug inhibiting the inflammatory factors, reducing blood viscosity, improving peripheral blood flow, and so on. Objective: The aim of the present study is to evaluate the effects of PX against Dimethyl nitrosamine (DMN)-inducing the damage to the reproductive parameter of male rats. Materials and Methods In this experimental study, 48 male Wistar rats (8 wk, 220-250 gr) were randomly assigned to eight groups (n = 6/each): normal control and DMN control groups (40 mg/kg); PX groups (25, 50, 100 mg/kg), and DMN + PX groups (25, 50, 100 mg/kg). Treatments were administered intraperitoneally and the gavage applied daily for 28 days. The sperm parameters, spermatogenesis index, total antioxidant capacity, testosterone level, and seminiferous tube diameter were assessed. Results The values of all parameters reduced significantly in the DMN control group compared to the normal control group (p < 0.001). The PX and PX + DMN treatments at all entirely doses improved all parameters significantly compared to the DMN control group (p < 0.001). Conclusion DMN caused detrimental effects on reproductive parameters. Also, no significant modifications were observed in PX treatments at all doses compared to the normal control group. PX compensated the toxic effect of DMN on reproductive parameters.

Introduction: Nicotine is the most important alkaloid compound in tobacco and is a major risk factor in the development of functional disorder of several organ systems. Some plants produce Curcumin, which has antioxidant and neuroprotective properties. This study was designed to evaluate the therapeutic effects of curcumin against nicotine injury on the hippocampus CA1 region of rats.Methods: In this study, 48 male Wistar rats were randomly assigned to eight groups: Normal control (saline) group, Nicotine control group (0.5 mg/kg); Curcumin groups (10, 30, and 60 mg/kg) and Nicotine + Curcumin groups (10, 30, and 60 mg/kg). Treatments were administered intraperitoneally daily for 28 days. Golgi staining technique investigated the number of dendritic spines. Cresyl violet staining method was used to determine the number of neurons in hippocampal region CA1. Griess technique was assessed to determine serum nitrite oxide level. Also, the Ferric reducing/antioxidant power (FRAP) method was applied to determine the total antioxidant capacity.Results: Nicotine administration significantly increased nitrite oxide level and decreased total antioxidant capacity as well as the number of neuronal dendritic spines and neurons compared to the normal control group (P < 0.01). In all Curcumin and Nicotine + Curcumin groups, the number of neurons, neuronal dendritic spines, and total antioxidant capacity increased significantly compared to the nicotine control group, while nitrite oxide level decreased significantly compared to the nicotine control group (P < 0.01).Conclusion: Curcumin administration can improve hippocampal CA1 region injury induced by nicotine.

BACKGROUND: Malathion is an organophosphate insecticide which disrupts the antioxidant system of the body. Resveratrol is a phytoestrogen and antioxidant of the red grape. AIM AND OBJECTIVE: This study was designed to evaluate the effects of resveratrol against toxic effects of malathion to the liver of rats. MATERIALS AND METHODS: In this study, 48 male rats were randomly assigned to 8 groups: control normal (saline) and malathion control-treated groups (50 mg/kg), resveratrol groups (2, 8, and 20 mg/kg), and malathion + resveratrol-treated groups (2, 8, and 20 mg/kg). Treatments were administered intraperitoneally daily for 14 days. Griess technique was assessed for determined serum nitrite oxide level. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase concentrations were determined for liver functional disturbances. In addition, thiobarbituric acid reactive species, antioxidant capacity, the diameter of hepatocytes, and the central hepatic vein (CHV) were investigated. RESULTS: Malathion administration significantly improved liver malondialdehyde (MDA) and nitrite oxide level, the mean diameter of CHV and hepatocyte, and liver enzymes and decreased tissue ferric-reducing ability of plasma (FRAP) level compared to the normal control group (P < 0.01). The resveratrol and resveratrol + malathion treatments at all doses significantly reduced the mean diameter of hepatocyte and CHV, liver enzymes, kidney MDA, and nitrite oxide levels and increased tissue FRAP level compared to the malathion control group (P < 0.01). CONCLUSION: It seems that resveratrol administration improved liver injury induced by malathion in rats.

Background and Aim: Use of medicinal plants is one of the methods to increase breast milk. Petroselinum crispum is a multipurpose herb in traditional medicine which contains essential amino acids, vitamins and numerous nutrients. This study aimed to determine the effects of Petroselinum crispum extract on milk production parameters in female rats. Material and Methods: In this experimental study, 32 Wistar female rats were randomly assigned to 4 groups; group1, control group (normal saline) and groups 2 to 4 (experimental groups). The experimental groups received various doses of Petroselinum crispum (100, 150, 200 mg/kg/day intraperitoneally) for 21 days. Petroselinum crispum extract was prepared. Prolactin hormone measurements were carried out based on RIA prolactin radio immune assay method. Using morphometrical techniques, prolactin receptor (PRLR) mRNA expression level and histological evaluation of mammary gland tissue were investigated. Data were analyzed by one way ANOVA test. Results: Petroselinum crispum administration increased significantly all the parameters in experimental groups compared to those in the control group (P

Introduction: University websites provide users with services and necessary information for professors, students, and other users. Considering the significant role of students for research development and progression, study intended to determine the satisfaction of students with the current website of Kermanshah University of Medical Sciences. Methods: This was a descriptive study in which 6 websites from medical, dental, pharmacy, midwifery, nursing, health and paramedical colleges were compared in terms of being up to date. The participants were selected randomly and 650 students from Kermanshah University of Medical Sciences were questioned about their satisfaction with university websites. Website evaluations were done through content analysis. Their validity was confirmed by five informatics experts. Using SPSSwin22 software, Cronbach's alpha coefficient was 0.86 which showed a good reliability. To determine the satisfaction of both male and female students regarding websites' updating, T-test and independent variance analysis were applied. Results: On the whole, 28 information items were extracted from the six websites under study and were classified into six groups: in formation on professors, department performance, filed of study, educational contents, and research. Students' satisfaction with information about professors and the departments was moderate but their satisfaction was even less regarding the research information of every department (p

Royal jelly (RJ) is a honeybee secretion, has numerous medicinal properties in particular antioxidant activities. Ischemia/reperfusion (I/R) is one of the main challenges in acute kidney damage. This study was designed to assess the anti-inflammatory and protective effects of RJ against I/R-induced renal disorders. Forty male rats were randomly divided into four groups (n = 10) as sham (0.9% saline) group, I/R group, RJ group (treated for 15 consecutive days by gavage with 300 mg/kg/day RJ), and I/R + RJ group that were pretreated for 15 consecutive days by gavage with 300 mg/kg/day of RJ. The I/R-induced renal inflammation was evaluated by determining leukocyte infiltration and mRNA expression level of intercellular adhesion molecule-1 and tumor necrotic factor-alpha (TNF-α). Antioxidant capacity of kidneys and thiobarbituric acid reactive species was measured in kidneys for the evaluation of oxidative stress. In addition, the diameter of renal glomeruli, kidney function indicators, and serum nitrite oxide (NO) levels was determined. The I/R increased the completely measured parameters, except the tissue ferric reducing/antioxidant power (FRAP) level, which was decreased compared to the sham group (P < 0.05). However, pretreatment with RJ reduced significantly blood urea nitrogen, kidney malondialdehyde, creatinine, glomerular diameter, leukocyte infiltration, levels of TNF-α, adhesion molecule-1 expression, and NO and increased tissue FRAP compared to the I/R group (P < 0.05). It seems that RJ administration improved I/R-induced acute kidney injury.

Nitrosamines are well-known carcinogenic agents. Humans are exposed to nitrosamines in various ways, the most important of which is the diet. Pentoxifylline is a xanthine derivative, which is used as a drug that inhibits inflammatory factors, reduces blood viscosity, improves peripheral blood flow, and increases oxygenation of tissue. This study was designed to evaluate the effects of pentoxifylline against damage induced by nitrosamine to the kidneys of rats. In this study, 48 male rats were randomly assigned to 8 groups: control normal group and nitrosamine control treated group (40 mg/kg); pentoxifylline groups (25, 50, 100 mg/kg) and nitrosamine + pentoxifylline treated groups (25, 50, 100 mg/kg). Treatments were administered either intraperitoneally (nitrosamine) or orally (pentoxifylline) on a daily basis for 28 days. The normalized kidney weight, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators, and serum nitrite oxide levels were investigated. Nitrosamine administration increased kidney malondialdehyde (MDA) level, kidney weight, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased significantly glomeruli number and tissue ferric reducing/antioxidant power (FRAP) level compared to the control normal group (P < 0.05). The pentoxifylline and pentoxifylline + nitrosamine treatments reduced BUN, kidney MDA level, creatinine, glomerular diameter, and nitrite oxide levels significantly at all doses and increased the glomeruli number, kidney weight, and tissue FRAP level compared to the nitrosamine control group (P < 0.05). It seems that pentoxifylline administration improved kidney injury induced by nitrosamine in rats.

Background: Alcohol consumption is capable of producing free radicals and inducing disturbance in body antioxidant. Falcaria vulgaris (F. vulgaris) is a vegetable and it has beneficial antioxidant effects. Materials and Methods: Forty-eight Wistar rats were divided randomly into eight groups (n = 6): control normal (saline) and ethanol (5g EtOH/kg body weight/24h) control groups, F. vulgaris groups (50, 100, and 150mg/kg), and F. vulgaris + ethanol treated groups (50, 100, and 150mg/kg). Treatments were administered intraperitoneally and through gavage daily for 12 weeks. Parameters related to the function and the histology of the kidneys were evaluated and statistically analyzed from kidney and blood serum samples with respect to the groups. Results: Ethanol administration increased significantly Bowman’s space, qualitative histopathology indices, kidney malondialdehyde (MDA) level, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased significantly total antioxidant capacity (TAC) level and diameter and number of renal corpuscles compared to that in the control normal group (P < 0.001). The F. vulgaris and F. vulgaris + ethanol treatments in a dose-dependent manner reduced significantly Bowman’s space, qualitative histopathology indices, kidney MDA level, BUN, creatinine, and nitrite oxide levels and increased significantly TAC level and diameter and number of renal corpuscles compared to that in the ethanol normal group (P < 0.001). Conclusion: It seems that F. vulgaris administration in a dose-dependent manner improved kidney injury induced by ethanol in rats.

Introduction: Pentoxifylline (PEN) is a xanthine derivative used as a drug to inhibit the inflammatory factors activity, reduce blood viscosity and improve peripheral blood flow. Proteins play the most important role in reproductive parameters. The aim of the present investigation is to evaluate the effects of PEN against high-protein diet (HPD)-induced damage to the reproductive parameter of male rats. Materials and Methods: In this experimental study, 48 male rats were randomly divided to 8 groups: sham (normal protein diet) and HPD (35% protein) groups; PEN groups (25, 50 and 100 mg/kg) and HPD + PEN groups (25, 50 and 100 mg/kg). Animals of the HPD group have fed with high protein daily for 10 months. Daily PEN treatment was injected intraperitoneally. The sperm parameters, spermatogenesis index, total antioxidant capacity, testosterone level and seminiferous tubule diameter were analysed. Results: The values of all reproductive parameters reduced significantly in the HPD group compared to the sham group (P < 0.01). The whole doses of PEN and PEN + HPD groups increased all parameters significantly compared to the HPD group (P < 0.01). Conclusions: No significant modifications were observed in PEN groups in all doses compared to the sham group. PEN relieved the effects of HPD on reproductive parameters.

Introduction: Proteins are the essential part of all organism cells. Nutrition plays the most important role in the structure and function of the brain. CA1 region belongs to hippocampus and plays a vital role in converting short-term to long-term memory. This study was designed to assess the effects of low-protein diet on hippocampal region CA1 and learning deficit in rats. Materials and Methods: In this study, 30 male rats were randomly assigned to two groups: control group and low-protein diet group (8% protein). Animals in a low-protein diet group have eaten food with low protein daily for 10 months. Body weight was measured. Transcardiac perfusion method was applied to tissue fixation. Passive avoidance learning of animals was examined by the shuttle-box apparatus technique. The number of dendritic spines was investigated by the Golgi staining technique. Furthermore, Cresyl violet staining method was used to determine the number of neurons in the hippocampal region CA1. Results: The passive avoidance learning of the low-protein diet rats was reduced significantly compared to the control ones (P < 0.001). Low-protein diet decreased the body weight, number of neuronal dendritic spines and neurons compared to the control group (P < 0.001). Conclusion: It seems that administration of low-protein diet had harmful effects of structure and function of hippocampal region CA1 in rats.

Objective: Carbophos (CAR) is an organophosphate that is most capable of producing free radicals and inducing alteration in some of the male reproductive parameters. Resveratrol (RES) is an herbal polyphenol and exerts beneficial antioxidant effects. This study aimed to evaluate the effects of RES against CAR-induced alteration in reproductive parameters of male rats. Methods: In this experimental study, 48 male rats were randomly assigned to eight groups: Group 1: Normal control (saline) group; Group 2: CAR control (250 mg/kg) group; Groups 3–5: 2, 8, and 20 mg/kg RES, respectively, groups; Groups 6–8: CAR plus 2, 8, and 20 mg/kg RES, respectively, groups. The agents were administered intraperitoneally and by gavage daily for 65 days. Sperm parameters, testis malondialdehyde (MDA) levels, total antioxidant capacity, testosterone levels, and germinal layer height were evaluated and compared among these groups. Results: No significant alterations were observed in RES groups (with different doses) compared to the normal control group (P > 0.05). The levels of all parameters except MDA (which decreased) significantly increased in the CAR plus RES (with different doses) groups compared to the CAR control group (P < 0.01). Conclusions: RES attenuates the toxic effect of CAR on some of the male reproductive parameters.

Objective: To evaluate effect of Phaseolus vulgaris (P. vulgaris) on the breastfeeding in female rats. Methods: This experimental study was done from May 2018 to December 2018 in the Anatomical Department of Medical School in Kermanshah University of Medical Sciences in Iran. In this study, after one-week adaptation and fertilization by male, 40 female rats within 20 days of pregnancy (on average, every mother had 10 newborns) were equally separated into four groups (animals were administrated after delivery of offspring). Group 1 was control group receiving normal saline interaperitoneally, and groups 2, 3, 4 were treatment groups receiving the dose of 20, 50, 100 mg/kg of P. vulgaris interaperitoneally respectively once a day for 60 days. The prolactin hormone was measured by radio immune assay, number and diameter of alveoli via histological and morphometrical examinations, and receptor prolactin gene expression by real-time polymerase chain reaction method. Results: P. vulgaris significantly improved alveoli’s number and diameter, prolactin hormone and receptor prolactin expression when compared to the control group (P

Introduction: Thymus vulgaris (T. vulgaris), with its antioxidant properties has therapeutic applications. Diabetes causes disruption in process of cardiac angiogenesis. Aim: To evaluate the therapeutic effects of T. vulgaris against destructive effects of diabetes in the field of coronary angiogenesis in rats. Materials and Methods: In this experimental study, 64 male rats were randomly sorted into 8 groups: 1) control group; 2-4) three extract groups (4.5, 9 and 18 mg/kg of T. vulgaris); 5) diabetic group; and 6-8) three diabetic + extract groups (4.5, 9 and 18 mg/kg of T. vulgaris) from April 2019 to November 2019. Diabetes was induced and various doses of T. vulgaris were administered for 60 consecutive days intraperitoneally. The serum level of Vascular Endothelial Growth Factor (VEGF) was determined by ELISA method, Nitrite Oxide (NO) measured by Griess assay, and the cardiac capillary density evaluated by immunohistochemistry assay. Data were analysed by one-way ANOVA test. Results: The values of VEGF, nitrite oxide, glucose and capillary density reduced significantly in diabetic group compared to the control group (p0.05). Conclusion: The hydroalcoholic extract of T. vulgaris represented no cardiac angiogenesis effects in normal and diabetic groups. This is due to the insufficient amounts of active biochemical ingredients, especially flavonoids in T. vulgaris.

This paper was published in the Journal of Herbmed Pharmacology in 2019 (doi: 10.15171/jhp.2019.47) (1). Based on an email received from the team of young researchers recently, we were informed that the results of this article (some figures and diagrams) have been published in several similar articles (2-5), which are considered ethical misconduct. This issue was investigated by the editorial team of the Journal of Herbmed Pharmacology. As a result, based on the Committee on Publication Ethics (COPE) guidelines, the editors decided to retract this paper. The authors were informed and advised on this serious ethical breach. This article has been retracted at the request of the corresponding author. The retracted article will remain online to maintain the scholarly record, but it will be watermarked on each page as ‘retracted’. References 1.Jalili C, Arji Rodsari B, Roshankhah S, Salahshoor MR. Effect of curcumin on hippocampus dentate gyrus injury induced by nicotine in rats. J Herbmed Pharmacol. 2019;8(4):320-327. doi: 10.15171/jhp.2019.47. 2.Roshankhah S, Abdolmaleki A, Jalili C, Salahshoor MR. Ameliorative Effect of Falcaria vulgaris on Nicotine-induced Injury on the Hippocampus Dentate Gyrus Region of Rats. Int J Pharm Invest. 2019;9(4):200-204. 3.Roshankhah S, Jalili C, Salahshoor MR. Falcaria vulgaris attenuates morphine toxicity in prefrontal cortex in rats. Egyptian Pharmaceutical Journal. 2019;18:276-84. doi: 10.4103/epj.epj_18_19. 4.Roshankhah S, Sadeghi E, Jalili C, Salahshoor MR. Impacts of Low‑Protein Diet on the Hippocampal CA1 Neurons and Learning Deficits in Rats. Adv Hum Biol. 2019;9:124-8. doi: 10.4103/AIHB.AIHB_31_19. 5.Salahshoor MR, Abdolmaleki A, Roshankhah S, Jalali A, Jalili C. Curcumin recovers the toxic effects of nicotine on hippocampus cornu ammonis 1 in rats. J Pharmacol Pharmacother. 2019;10:85-92. doi: 10.4103/jpp.JPP_38_19.

This paper was published in the Journal of Herbmed Pharmacology in 2020 (doi: 10.15171/jhp.2020.07) (1). Based on an email received from the team of young researchers recently, we were informed that the results of this article have been published in another study (2), which is considered ethical misconduct. This issue was investigated by the editorial team of the Journal of Herbmed Pharmacology. As a result, based on the Committee on Publication Ethics (COPE) guidelines, the editors decided to retract this paper. The authors were informed and advised on this serious ethical breach. This article has been retracted at the request of the corresponding author. The retracted article will remain online to maintain the scholarly record, but it will be watermarked on each page as ‘retracted’. References 1. Jalili C, Abdolmaleki A, Roshankhah S, Salahshoor MR. Histopathological and biomedical parameters determination in the protective effect of crocin on hepatotoxicity induced by methotrexate in rats. J Herbmed Pharmacol. 2020;9(1):48-54. doi: 10.15171/jhp.2020.07. 2. Salahshoor MR, Abdolmaleki A, Jalili C, Roshankhah S, Ziapour A. Determination of histopathological and biomedical parameters in protective effects of Petroselinum crispum on hepatotoxicity induced by dichlorvos in male Wistar rats. Comp Clin Path. 2020;29(2):501-9. doi: 10.1007/s00580-019-03087-7.

This paper was published in the Journal of Herbmed Pharmacology in 2020 (doi: 10.15171/jhp.2020.09) (1). Based on an email received from the team of young researchers recently, we were informed that this published paper presented some data as same as data presented in two other published papers (2,3), which are considered as ethical misconduct. This issue was investigated by the editorial team of the Journal of Herbmed Pharmacology. As a result, based on the Committee on Publication Ethics (COPE) guidelines, the editors decided to retract this paper. The authors were informed and advised on this serious ethical breach. This article has been retracted at the request of the corresponding author. Given that both studies on hepatotoxicity were performed and published by the authors at the same time. Some data and Excel files were inadvertently moved from the first article (Determination of histopathological and biomedical parameters in protective effects of Petroselinum crispum on hepatotoxicity induced by dichlorvos in male Wistar rats) to the second article (Histopathological and biomedical parameters determination in the protective effect of crocin on hepatotoxicity induced by methotrexate in rats) and caused the similarity of figures 1, 2 and 5 in the two articles. The retracted article will remain online to maintain the scholarly record, but it will be watermarked on each page as ‘retracted’. References 1. Jalili C, Abdolmaleki A, Roshankhah SH, Salahshoor MR. Effects of gallic acid on rat testopathy following morphine administration: an experimental study. J Herbmed Pharmacol. 2020;9(1):61-67. doi: 10.15171/jhp.2020.09. 2. Salahshoor MR, Faramarzi A, Roshankhah S, Jalili C. The protective effect of Pentoxifylline on testopathy in male rats following Dimethyl Nitrosamine administration: An experimental study. Int J Reprod BioMed. 2019;17(10):727-38. 3. Salahshoor MR, Abdolmaleki A, Jalili C, Roshankhah S. Can pentoxifylline recover reproductive parameters’ damage induced by high-protein diet in male rats? Advances in Human Biology. 2019;9(3):203-9.

Background: Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim of this study was to evaluate the effects of genistein against morphine damages on mouse liver. Methods: Between May 2017 and March 2018, 48 male mice were divided into six groups (n = 8 in each group). Various doses of genistein (25 and 50 mg/kg) and morphine plus genistein (25 and 50 mg/kg) were administered intraperitoneally to 48 male mice for 20 consequent days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum nitric oxide (NO) levels, liver weight, and the diameter of hepatocytes and central hepatic vein were studied and compared using one-way analysis of variance. Results: Morphine administration significantly increased the mean diameter of the central hepatic vein (22.76 ± 1.9 μm vs. 15.04 ± 0.60 μm, χ2 = 21.814, P = 0.001) and hepatocytes (3.03 ± 0.10 μm vs. 1.10 ± 0.05 μm, χ2 = 9.873, P = 0.001) respectively, blood serum NO level (38.00% ± 2.09% vs. 18.72% ± 4.40%, χ2 = 20.404, P < 0.001), liver enzyme level (AST: 111.80 ± 5.10 ng/ml vs. 81.93 ± 2.20 ng/ml, χ2 = 32.201, P < 0.0001; ALT: 45.14 ± 4.10 ng/ml vs. 35.49 ± 2.50 ng/ml, χ2 = 18.203, P < 0.0001; and ALP: 3.28 ± 0.20 ng/ml vs. 2.14 ± 0.10, χ2 = 5.04, P < 0.0001, respectively), and decreased liver weight (18.50 ± 0.90 g vs. 27.15 ± 0.50 g, χ2 = 22.415, P = 0.001) compared to saline group (0.535–0.750, P < 0.0001). However, administration of genistein plus morphine significantly enhanced liver weight (25 mg/kg: 21.15 ± 2.13 g vs. 18.50 ± 0.90 g, χ2 = 19.251, P < 0.0001; 50 mg/kg: 21.20 ± 1.00 g vs. 18.5 ± 0.9 g, χ2 = 19.502, P < 0.0001, respectively) and reduced the mean diameter of hepatocyte (25 mg/kg: 2.17 ± 0.30 μm vs. 3.03 ± 0.10 μm, χ2 = 22.780, P = 0.001; 50 mg/kg: 2.01 ± 0.20 μm vs. 3.03 ± 0.10 μm χ2 = 7.120, P = 0.001, respectively), central hepatic vein (25 mg/kg: 19.53 ± 1.00 μm vs. 22.76 ± 1.90 μm, χ2 = 20.681, P = 0.001; 50 mg/kg: 19.44 ± 1.20 μm vs. 22.76 ± 1.90 μm, χ2 = 18.451, P = 0.001, respectively), AST (25 mg/kg: 95.40 ± 5.20 ng/ml vs. 111.80 ± 5.010 ng/ml, P < 0.0001; 50 mg/kg: 90.78 ± 6.00 ng/ml vs. 111.80 ± 5.10 ng/ml, χ2 = 17.112, P < 0.0001, respectively), ALT (25 mg/kg: 35.78 ± 5.01 ng/ml vs. 45.14 ± 4.10 ng/ml, χ2 = 15.320, P < 0.0001; 50 mg/kg: 33.78 ± 2.60 ng/ml vs. 45.14 ± 4.10 ng/ml, χ2 = 14.023, P < 0.0001, respectively), ALP (25 mg/kg: 2.35 ± 0.30 ng/ml vs. 3.28 ± 0.20 ng/ml, χ2 = 4.101, P < 0.0001; 50 mg/kg: 2.34 ± 0.10 ng/ml vs. 3.28 ± 0.20 ng/ml, χ2 = 2.033, P < 0.0001, respectively), and NO levels (25 mg/kg: 25.92% ± 2.30% vs. 38% ± 2.09%, χ2 = 17.103, P < 0.0001; 50 mg/kg: 24.74% ± 4.10% vs. 38% ± 2.09%, χ2 = 25.050, P = 0.001, respectively) compared to morphine group. Conclusion: It seems that genistein administration might improve liver damages induced by morphine in mice.

Objective: Malathion is the most organophosphates which capable to produce free radicals and induce disturbance on some of male reproductive parameter. Resveratrol is an herbal polyphenol and it has been beneficial antioxidant effects during short-term administration. This study was designed to evaluate the effects of Resveratrol against damage induced by Malathion to the reproductive parameter of male rats. Materials and methods: In this experimental study, 48 male rats were randomly assigned to 8 groups: normal control (saline) and Malathion control (250 mg/kg) groups; Resveratrol groups (2, 8, 20 mg/kg) and Malathion + Resveratrol (2, 8, 20 mg/kg). Treatments were administered intraperitoneally and gavage daily for 65 days. The sperm parameters, testis malondialdehyde (MDA), total antioxidant capacity (TAC), testosterone level and germinal layer height were evaluated and statistically analyzed. Results: The results displayed that the values of all parameters except MDA level (which increased) reduced significantly in the Malathion control group compared to the normal control group (p < 0.001). The Resveratrol and Resveratrol + Malathion treatments at all doses increased significantly all parameters except MDA level (which decreased) compared to the Malathion control group (p < 0.001). No significant modifications were observed in all Resveratrol groups compared to the normal control group (p > 0.05). Conclusion: Resveratrol attenuates toxic effect of Malathion on some of male reproductive parameters.

Introduction: The region of Cornu Ammonis 1 (CA1) in hippocampus has an obvious role in alteration of short-term memory to long-term. Proteins, as a crucial aspect of the cells, are involved in the structure and function of hippocampus. Aim: To study the effects of High Protein Diet (HPD) on CA1 and learning defect in rats. Materials and Methods: In this experimental study, 20 Wistar male rats were divided into two groups by random samplling: the groups of control (normal diet including 14% protein was used) and HPD (35% protein). Animals in HPD group were daily fed HPD for 10 months. Body weight was measured. Transcardiac perfusion procedure was applied for tissue fixation. Passive avoidance learning of animals was examined by shuttle-box apparatus technique. The number of dendritic spines was investigated by Golgi staining protocol. Also, Cresyl Violet staining was used to determine the number of neurons in the hippocampal area of CA1. Kolmogorov-Smirnov test was applied to confirm the normal distribution of data and t-test was used for determination of differences among the groups. SPSS version 16 was used for data analyses. Results: The Passive Avoidance Learning of the HPD rats was significantly higher compared to the control group (p-value

Introduction: Alcoholic liver disease is the most important side effect of alcohol consumption. Falcaria vulgaris (F. vulgaris) plant or long leaf contains antioxidant and antimicrobial ingredients. This plant is consumed in western Iran as a vegetable in the spring. Aim: To evaluate the effects of F. vulgaris against toxic effects of ethanol on the liver of rats. Materials and Methods: In this study, hydroalcoholic extract of F. vulgaris was prepared. Sixty four Wistar rats (male rats) were randomly assigned to eight groups: control normal and ethanol control groups; F. vulgaris groups (50, 100, 150 mg/ kg) and ethanol + F. vulgaris treated groups (50, 100, 150 mg/kg). Treatments were administered by gavage daily for 28 days. Griess technique was assessed for determined Serum nitric oxide level. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) concentrations were determined for liver functional disturbances. In addition, liver weight, total antioxidant capacity, the diameter of hepatocytes and the Central Hepatic Vein (CHV) were investigated. Results: Ethanol enhanced significantly total antioxidant capacity, nitric oxide level, the mean diameter of CHV, and hepatocyte and liver enzymes and significantly decreased liver weight compared to the normal control group (p

Objective: Falcaria Vulgaris (F.Vulgaris) is a multipurpose herb in traditional medicine, containing essential amino acids, vitamins and numerous nutrients. The aim of this study was to determine the effects of F.Vulgaris on the on the milk production parameters in rats. Materials and methods: In this experimental study, 32 wistar female rats were equally divided into 4 groups; group1, control group and group2-4, experimental groups by various doses of F.Vulgaris (20, 50, 100 mg/kg) injected interaperitoneally once a day for 21 consecutive days. The milk production parameters including, diameter and number of alveoli, prolactin hormone level and receptor prolactin (PRLR) gene expression in mammillary gland tissue were measured and compared. Results: The results indicated that F.Vulgaris significantly increased diameter and number of alveoli, prolactin hormone level and PRLR gene expression compared to control group (p < 0.05). Conclusion: F.Vulgaris extract has positive effects on the milk production parameters in mammary glands.

The color of turmeric (薑黃 jiāng huáng) is because of a substance called curcumin. It has different pharmacological effects, such as antioxidant and anti-inflammatory properties. Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in the liver and causes devastating effects. This study was designed to evaluate the protective role of curcumin against nicotine on the liver in mice. Forty-eight mice were equally divided into eight groups; control (normal saline), nicotine (2.5 mg/kg), curcumin (10, 30, and 60 mg/kg) and curcumin plus nicotine-treated groups. Curcumin, nicotine, and curcumin plus nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. The results indicated that nicotine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein, liver enzymes level, and blood serum nitric oxide level compared with the saline group (p

Background: The predominant phytoestrogen in soy and derived products is the isoflavone Genistein. Genistein has antioxidant properties. Morphine is a main psychoactive chemical in opium that can increase the generation of free radicals and therefore it could adversely affects the spermatogenesis. Objective: The main goal was to investigate whether the Genistein could protect morphine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone and nitric oxide in blood serum. Materials and Methods: In this study, various doses of Genistein (0, 1, 2, and 3 mg/kg) and Genistein plus morphine (0, 1, 2, and 3 mg/kg) were administered interaperitoneally to 48 male mice for 30 consequent days. These mice were randomly assigned to 8 groups (n=6) and sperm parameters (sperm cells viability, count, motility and morphology), testis weight and histology, testosterone hormone (ELISA method), FSH and LH hormones (immunoradiometry) and serum nitric oxide (griess assay) were analyzed and compared. Results: The results indicated that morphine administration significantly decreased testosterone (0.03 ng/mg) LH and FSH level, histological parameters, count, viability (55.3%), morphology and motility of sperm cells (1%), testis weight (0.08 gr) and increase nitric oxide compared to saline group (p=0.00). However, administration of Genistein and Genistein plus morphine significantly boosted motility, morphology, count, viability of sperm cells, seminiferous tubules diameter, germinal thickness, testosterone, LH and FSH while decrease nitric oxide level in all groups compared to morphine group (p

Crocin, a bioactive molecule of saffron can be purely isolated from the saffron extract. It has different pharmacological effects such as antioxidant and anticancer activities. Morphine is an opioid analgesic drug. It is mainly metabolized in liver and causes devastating effects. It can increase the generation of free radicals. This study was designed to evaluate the protective role of crocin against morphine-induced toxicity in the mouse liver. In this study, various doses of crocin (12.5, 25 and 50 mg/kg) and crocin plus morphine were administered interaperitoneally once daily to 48 male mice for 20 consecutive days. These mice were randomly assigned to 8 groups of 6 each. The liver weight and histology, aspartate amino transferase, alanine aminotransferase, alkaline phosphatase (ALP) and serum nitric oxide levels were studied. The results indicated that morphine administration significantly decreased liver weight and increased the mean diameter of hepatocyte, central hepatic vein diameters, liver enzyme levels, and blood serum nitric oxide level compared to saline group (P<0.05). However, crocin administration significantly boosted liver weight and decreased the mean diameter of hepatocyte, central hepatic vein, liver enzymes and nitric oxide levels in all groups compared to the group received morphine alone (P<0.05). It seems that crocin administration could protect the liver damage induced by morphine. The antioxidant effect of crocin may be a major reason for its positive impact on liver parameters.

Objective(s): Adipose derived stem cells (ADSCs) can be engineered to express bone specific markers. The aim of this study is to evaluate repairing tibia in animal model with differentiated osteoblasts from autologous ADSCs in alginate scaffold. Materials and Methods: In this study, 6 canine’s ADSCs were encapsulated in alginate and differentiated into osteoblasts. Alkaline phosphatase assay (ALP) and RT-PCR method were applied to confirm the osteogenic induction. Then, encapsulated differentiated cells (group 1) and cell-free alginate (group 2) implanted in defected part of dog's tibia for 4 and 8 weeks. Regenerated tissues and compressive strength of samples were evaluated by histological and Immunohistochemical (IHC) methods and Tensometer Universal Machine. Results: Our results showed that ADSCs were differentiated into osteoblasts in vitro, and type I collagen and osteocalcin genes expression in differentiated osteoblasts was proved by RT-PCR. In group 2, ossification and thickness of trabecula were low compared to group 1, and in both groups woven bone was observed instead of control group's compact bone. Considering time, we found bone trabeculae regression and ossification reduction after 8 weeks compared with 4 weeks in group 2, but in group 1 bone formation was increased in 8 weeks. Presence of differentiated cells caused significantly more compressive strength in comparison with group 2 (P-value ≤0.05). Conclusion: This research showed that engineering bone from differentiated adipose-derived stem cells, encapsulated in alginate can repair tibia defects.

Objective(s):Osteoarthritis (OA) is globally one of the most common diseases from the middle age onwards. Cartilage is an avascular tissue therefore it cannot be repaired in the body. Conservative treatments have failed as a good remedy and cell therapy as a decisive cure is needed. One of the best and easily accessible cell sources for this purpose is adipose-derived stem cells which can be differentiated into chondrocytes by tissue engineering techniques. Chemical and physical inducers have a key role in stem cell – chondrocyte differentiation. We have tried to determine the role of electric fields (EF) in promoting this kind of chondrogenesis process. Materials and Methods: Human adipose derived stem cells (ADSCs) were extracted from subcutaneous abdominal adipose tissue during cesarean section. A high frequency (60 KHz) EF (20 mv/cm), as a physical inducer for chondrogenesis in a 3D micromass culture system of ADSCs was utilized. Also, MTT, ELISA, flow cytometry, and real-time PCR techniques were used for this study. Results: We found that using physical electric fields leads to chondrogenesis. Furthermore, results show that using both physical (EF) and chemical (TGFβ3) inducers simultaneously, has best outcomes in chondrogenesis, and expression of SOX9 andtype II collagen genes. It also causes significant decreased expression of type I and X collagen genes in pure EF group compared with control group. Conclusion:The EF was found as a proper effective inducer in chondrogenic differentiation of human ADSCs micromass culture.

Background and Objectives: Studies suggest that FAS/FASL polymorphisms are associated with male infertility; however, their results are still inconclusive. Therefore, this systematic review and meta-analysis aimed to summarize and clarify the overall association of FAS/FASL polymorphisms and risk of male infertility. Materials and Methods: Our search was conducted on the databases of Science Direct, PubMed and Google Scholar. For performing the meta-analysis, pooled odds ratio (OR) values with 95% confidence interval (CI) was applied in order to analyze the strength of association between the FAS/FASL polymorphisms and risk of male infertility. A total of seven relevant studies published up to September 2018 were considered. Results: FASL-844C/T genotype results of 559 patients and 623 healthy individuals were included in our study. For FAS-670A/G genotype effect, 751 patients and 821 healthy individuals were explored. Results showed that all analysis models including dominant, recessive and allelic models of FASL-844C/T and FAS-670A/G polymorphism had no significant effect on infertility in men (p > 0.05 and p > 0.05, respectively). According to sensitivity analysis, our results were stable. Conclusion: We demonstrated that FAS/FASL polymorphisms might not be an effective factor on male reproductive health. For precise determination of FAS/FASL polymorphisms effects on male infertility, large-scale case-control studies should be performed.

Background: Diabetes can increase the generation of free radicals and can be harmfully effective in spermatogenesis. Crocin is a carotenoid and is accountable for the red color of saffron. Crocin has shown numerous pharmacological actions such as antioxidant roles and radical scavenging. The aim of this study was to determine the effects of crocin on sperm parameters and the diameter of seminiferous tubules in diabetic rats. Materials and Methods: In this experimental study, diabetic rats were induced by Streptozotocin (STZ) (60 mg/kg). Sixty-four rats were equally divided into the following eight groups; (1) normal control group, (2–4) crocin groups, receiving various doses of crocin (12.5, 25, and 50 mg/kg), (5) diabetic control group, and (6–8) diabetic groups, receiving STZ plus crocin (12.5, 25, and 50 mg/kg) injected intraperitoneally once a day for 28 consecutive days. The sperm count, motility, morphology, viability, spermatogenesis index (SI), and the diameter of seminiferous tubules were examined and compared. Results: The results demonstrated that count, motility, viability, normal sperm morphology, SI, and the diameter of seminiferous tubules decreased significantly in the diabetic control group compared to the normal control group (P < 0.05). However, in the diabetic groups, count, motility, normal morphology, viability, SI, and the diameter of seminiferous tubules enhanced significantly in total doses compared to those of the diabetic control group (P < 0.05). Conclusion: It seems that, as a strong antioxidant, crocin could compensate for the toxicity induced through STZ and raise the quality of some sperm parameters.

Background: The nicotine content of cigarettes plays a key role in the pathogenesis of kidney disease. Harmine is a harmal-derived alkaloid with antioxidant properties. This study was designed to evaluate the effects of harmine against nicotine-induced damage to the kidneys of mice. Methods: In this study, 64 male mice were randomly assigned to eight groups: saline and nicotine-treated groups (2.5 mg/kg), harmine groups (5, 10, and 15 mg/kg), and nicotine (2.5 mg/kg) + harmine-treated groups (5, 10, and 15 mg/kg). Treatments were administered intraperitoneally daily for 28 days. The weights of the mice and their kidneys, kidney index, glomeruli characteristics, thiobarbituric acid reactive species, antioxidant capacity, kidney function indicators, and serum nitrite oxide levels were investigated. Results: Nicotine administration significantly improved kidney malondialdehyde (MDA) level, blood urea nitrogen (BUN), creatinine, and nitrite oxide levels and decreased glomeruli number and tissue ferric reducing/antioxidant power (FRAP) level compared to the saline group (P < 0.05). The harmine and harmine + nicotine treatments at all doses significantly reduced BUN, kidney MDA level, creatinine, glomerular diameter, and nitrite oxide levels and increased the glomeruli number and tissue FRAP level compared to the nicotine group (P < 0.05).Conclusions: It seems that harmine administration improved kidney injury induced by nicotine in mice.

Background: P300 is an enzyme that acetylates histones during stress. It alsoacetylates several non-histone proteins, including P53 which is the most important tumorsuppressor gene. P53 plays an important role in the apoptosis of tumor cells. Hereby,this study describes the potency of cholera toxin B subunit as a P300 activator to induceapoptosis in a breast cancer cell line (MCF-7) and a lung fibroblast cell line (MRC-5)as a non-tumorigenic control sample. Methods: MCF-7 and MRC-5 were cultured in RPMI-1640 and treated with orwithout cholera toxin B subunit at the concentration of 85.43 μmol/L, based on the half-maximal inhibitory concentration index at different times (24, 48 and 72 h). Thepercentage of apoptotic cells was measured by flow cytometry. Real-time quantitativeRT-PCR was performed to estimate the mRNA expression of P300 in MCF-7 and MRC-5 with cholera toxin B subunit at different times. We used the ELISA and Bradford proteintechniques to detect levels of total and acetylated P53 protein generated in MCF-7 andMRC-5. Results: Our findings indicated that the cholera toxin B subunit effectively andsignificantly induced more apoptosis in MCF-7 compared to MRC-5. We showed thatexpression of P300 up-regulated by increasing the time of the cholera toxin B subunittreatment in MCF-7 but not in MRC-5. In addition, the acetylated and total P53protein levels increased more in MCF-7 cells than in MRC-5 cells.Conclusion: Cholera toxin B subunit induced significant cell death in MCF-7, butit could be well tolerated in MRC-5. Therefore, cholera toxin B subunit can besuggested as an anti-cancer agent.

Background: Sirtuin1 is an enzyme that deacetylates histones and several non-histone proteins including P53 during the stress. P300 is a member of the histone acetyl transferase family and enzyme that acetylates histones. Hereby, this study describes the potency combination of Salermide as a Sirtuin1 inhibitor and cholera toxin B (CTB) as a P300 activator to induce apoptosis Michigan Cancer Foundation-7 (MCF-7) and MRC-5. Methods: Cells were cultured and treated with a combination of Salermide and CTB respectively at concentrations of 80.56 and 85.43 μmol/L based on inhibitory concentration 50 indexes at different times. The percentage of apoptotic cells were measured by flow cytometry. Real-time polymerase chain reaction was performed to estimate the messenger ribonucleic acid expression of Sirtuin1 and P300 in cells. Enzyme linked immunosorbent assay and Bradford protein techniques were used to detect the endogenous levels of total and acetylated P53 protein generated in both cell lines. Results: Our findings indicated that the combination of two drugs could effectively induced apoptosis in MCF-7 significantly higher than MRC-5. We showed that expression of Sirtuin1 and P300 was dramatically down-regulated with increasing time by the combination of Salermide and CTB treatment in MCF-7, but not MRC-5. The acetylated and total P53 protein levels were increased more in MCF-7 than MRC-5 with incubated combination of drugs at different times. Combination of CTB and Salermide in 72 h through decreasing expression of Sirtuin1 and P300 genes induced acetylation of P53 protein and consequently showed the most apoptosis in MCF-7 cells, but it could be well-tolerated in MRC-5. Conclusion: Therefore, combination of drugs could be used as an anticancer agent.

Background Sildenafil is a selective inhibitor of cyclic-guanosine monphosphat-specific phosphodiesterase type 5. It increases intracellular nitric oxide (NO) production in some cells. There are reports on its positive effect on uterine circulation, endometrial thickness, and infertility improvement. Endometrial epithelial cells (EEC) play an important role in embryo attachment and implantation. The present work investigates the effect of sildenafil on human EEC and their NO secretion in vitro. Materials and Methods In this experimental in vitro study, endometrial biopsies (n=10) were washed in a phosphate buffered solution (PBS) and digested with collagenase I (2 mg/ml in DMEM/ F12 medium) at 37°C for 90 minutes. Epithelial glands were collected by sequential filtration through nylon meshes (70 and 40 μm pores), respectively. Epithelial glands were then treated with trypsin to obtain individual cells. The cells were counted and divided into four groups: control and 1, 10, and 20 μM sildenafil concentrations. Cells were cultured for 15 days at 37ºC and 5% CO2; the media were changed every 3 days, and their supernatants were collected for the NO assay. NO was measured by standard Greiss methods. Data were analyzed by one way ANOVA. Results There was no significant difference between groups in cell count and NO secretion, but the level of NO increased slightly in the experimental groups. The 10 μM dose showed the highest cell count. EEC morphology changed into long spindle cells in the case groups. Conclusion Sildenafil (1, 10, and 20 μM) showed a mild proliferative effect on human EEC numbers, but no significant change was seen in NO production.

Background: Morphine is a pain medication .It is mostly processed in liver and reasons disturbing effects. It can increase the production of free radicals. Thymoquinone is a phytochemical compound found in the plant Nigella sativa. It has diverse pharmacological properties such as antioxidant and anticancer. This study was intended to assess the effects of thymoquinone against morphine damages on the liver of mice. Methods: In this study, various doses of thymoquinone (4.5, 9, and 18 mg/kg) and thymoquinone plus morphine wasadministered (once a day) intraperitoneally to 48 male mice for 20 consequent days. These mice were randomly assigned to eight groups (n = 6). Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, serum nitric oxide (NO) levels, liver weight, and histology have been studied. Results: The results indicated that morphine administration significantly increased the mean diameter of central hepatic vein and hepatocyte, blood serum NO level, liver enzymes level, and decreased liver weight compared to saline group (P < 0.05). However, thymoquinone and thymoquinone plus morphine administration significantly enhanced liver weight and reduced the mean diameter of hepatocyte, central hepatic vein, liver enzymes, and NO levels in all groups compared to morphine group (P < 0.05). Conclusions: It seems that antioxidant effect of thymoquinone could protect damage of liver parameters against morphine toxicity.

Background: Thymoquinone as the main active component of Nigella sativa might have a various pharmacological effects such as antiapoptotic and antioxidant. Morphine is commonly used for the treatment of severe pain that can increase the generation of free radicals and affects the spermatogenesis. This study was designed to evaluate protective effects of thymoquinone against morphine-induced damages, sperm viability, count, motility, morphology and testis histology, and nitric oxide and testosterone hormone of the mice. Materials and Methods: In this experimental study, we divided 48 mice into eight groups (n = 6); various doses of thymoquinone (2, 10, and 20 mg/kg) and morphine (20 mg/kg) plus thymoquinone (2, 10, and 20 mg/kg) were administered intraperitoneally to 48 male mice for 30 consequent days. Male reproductive parameters including testis weight, testosterone hormone, serum nitric oxide, germinal thickness, sperm morphology, count, viability, and motility were analyzed and compared. Results: The results indicated that morphine administration significantly decreased germinal thickness, testis weight, testosterone level, viability, morphology, count, and motility of sperm and increased nitric oxide as compared to saline group (P < 0.05). However, increasing the dose of thymoquinone in the thymoquinone and thymoquinone plus morphine groups significantly decreases nitric oxide level (P < 0.05) while significantly boosted motility, morphology, count, viability of sperm cells, germinal thickness, and testosterone hormone in all groups as compared to morphine group (P < 0.05). Conclusion: It seems that thymoquinone administration could increase the quality some of spermatozoa and improves morphine-induced adverse effects on reproductive parameters in male mice

Background: Since when the cartilage damage (e.g., with the osteoarthritis) it could not be repaired in the body, hence for its reconstruction needs cell therapy. For this purpose, adipose-derived stem cells (ADSCs) is one of the best cell sources because by the tissue engineering techniques it can be differentiated into chondrocytes. Chemical and physical inducers is required order to stem cells to chondrocytes differentiating. We have decided to define the role of electric field (EF) in inducing chondrogenesis process. Materials and Methods: A low frequency EF applied the ADSCs as a physical inducer for chondrogenesis in a 3D micromass culture system which ADSCs were extracted from subcutaneous abdominal adipose tissue. Also enzyme-linked immunosorbent assay, methyl thiazolyl tetrazolium, real time polymerase chain reaction and flowcytometry techniques were used for this study. Results: We found that the 20 minutes application of 1 kHz, 20 mv/cm EF leads to chondrogenesis in ADSCs. Although our results suggest that application of physical (EF) and chemical (transforming growth factor-β3) inducers at the same time, have best results in expression of collagen type II and SOX9genes. It is also seen EF makes significant decreased expression of collagens type I and X genes. Conclusion: The low frequency EF can be a good motivator to promote chondrogenic differentiation of human ADSCs.

Background: Nicotine is a major pharmacologically active substance in cigarette smoke. It is mainly metabolized in liver and causes devastating effects. Crocin is the chemical ingredient primarily responsible for the color of saffron. It has different pharmacological effects such as antioxidant and anticancer. This study was designed to evaluate the protective role of crocin against nicotine on the liver of mice. Methods: Forty-eight mice were equally divided into 8 groups; control (normal saline), nicotine (2.5 mg/kg), crocin (12.5, 25 and 50 mg/kg) and crocin plus nicotine treated groups. Saline, crocin, nicotine and crocin/nicotine (once a day) were intraperitoneally injected for 4 weeks. The liver weight and histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum nitric oxide levels have been studied. Results: The results indicated that nicotine administration significantly decreased liver weight (48.37%) and increased the mean diameter of hepatocyte (239%), central hepatic vein (28.45%), liver enzymes level (ALP 29.43%, AST 21.81%, ALT 21.55%), and blood serum nitric oxide level (57.18%) compared to saline group (P < 0.05). However, crocin and crocin plus nicotine administration significantly boosted liver weight (49.54%) and decreased the mean diameter of hepatocyte (40.48%), central hepatic vein (15.44%), liver enzymes (ALP 22.02%, AST 19.05%, ALT 23.11%), and nitric oxide levels (35.80%) in all groups compared to nicotine group (percentages represent the maximum dose) (P < 0.05). Conclusions: Crocin showed its partly protective effect against nicotine-induced liver toxicity.