Protective effects of diosmin on doxorubicin-induced testicular toxicity in rat.

Doxorubicin (DOX) can be applied to treat several cancers. DOX-induced oxidative stress causes testicular damage. Diosmin (DIO), as a potent antioxidant, reduces many drugs' side effects. We determined DIO therapeutic effects on DOX-related testicular toxicity. Forty rats were assigned to five groups as control, DOX (2.5 mg/kg six i.p. injections at equal intervals over two weeks), DOX + DIO (25, 50, 100 mg/kg, orally, daily, for two weeks) groups. Oxidative and antioxidant markers, fertility parameters levels, sperm parameters, and a histopathological examination were analyzed. DOX group showed a significant decrease in the number of spermatogonia, primary spermatocytes, and sertoli cells, seminiferous tubular diameter, seminiferous luminal diameter, and seminiferous epithelial height. Moreover, testosterone levels, glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities showed a significant decrease. Furthermore, nitric oxide (NO) and malondialdehyde (MDA) contents and also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed a significant increase in the DOX group compared to the control group. DIO improved DOX-related alterations in levels of hormones, spermatogonia, spermatocytes, and sertoli cell number, and seminiferous diameters (tubular, luminal, and epithelial height). Furthermore, GSH level, SOD, GPx, and CAT activities showed a significant increase, and MDA and NO contents showed a significant decrease in the DOX + DIO group than the DOX group. The results indicate that DIO mitigate DOX-induced testicular toxicity by its anti-oxidant activity.

Determination of the effectiveness of Dorema ammoniacum gum on wound healing: an experimental study.

OBJECTIVE: For a long time, natural compounds have been used to accelerate wound healing. In this study, the topical effects of ammoniacum gum extract on wound healing were investigated in white male rats. METHOD: Following skin wound induction in aseptic conditions, 48 Wistar rats were divided into six equal groups; phenytoin cream 1% (standard), untreated (control), Eucerin (control), and 5%, 10% and 20% ointments of Dorema ammoniacum gum extract (treatment groups). All experimental groups received topical drugs daily for 14 days. The percentage of wound healing, hydroxyproline content, histological parameters, and growth factors (endothelial growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-α) were measured in experimental groups. RESULTS: The areas of the wounds in the treatment groups were significantly decreased compared with the wound areas of control groups at 5, 7 and 10 days after wounding. On the 12th day, the wounds in the treatment groups were completely healed. Hydroxyproline contents were significantly increased in the treatment groups compared with the control groups (p<0.001). In histological evaluation, the re-epithelialisation, increasing thickness of the epithelial layer, granulation tissue and neovascularisation parameters in the treatment groups showed significant increases compared with the control groups. Also, serum levels of TGF-ß, PDGF, EGF and VEGF in the treatment groups were significantly increased compared to the control groups. CONCLUSION: The topical application of ammoniacum gum extract significantly increases the percentage of wound healing in rats and reduces the time of wound closure.

Determination of the Effectiveness of Topical Product of Commiphora Mukul Oleo Gum Resin on Dermal Wound Healing: An Experimental Study.

In Persian Medicine, many plants have been used in wound healing for thousands of years, and recent evidence indicates the beneficial effects of plant extracts on healing skin wounds. Commiphora mukul oleo gum resin has been considered for a long time due to its various properties such as milk-enhancing, diuretic, and healing the mouth and larynx wounds. The present study aimed to evaluate the effect of Commiphora mukul oleo gum resin on wound healing in rats. Forty-two albino Wistar rats have randomly divided into six groups: The first group was without treatment, the second group was treated with Eucerin, the third group was treated with phenytoin cream %1, the fourth to sixth groups were treated with Commiphora mukul ointment 2%, 4%, and 8% respectively. Treatment was performed once a day for 14 days, and the wound area was measured daily. At the end of the experiment, blood samples were taken to measure vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The histological evaluation and the strength test of the repaired tissue were performed. The results showed that seven days after treatment, the wound area decreased significantly in the groups treated with mukul gum extract compared to the control groups (p0.05). At the end of the experiment, there was no significant difference in wound area reduction between the groups. Commiphora mukul gum extract increased VEGF and significantly improved skin elasticity. The results of this study indicate the Wound healing potential of Commiphora mukul.

Naringenin: a potential natural remedy against methotrexate-induced hepatotoxicity in rats.

Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.

Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation.

BACKGROUND: We aimed to study the beneficial property of chrysin (CHR) by targeting its antioxidant and anti-inflammatory effects on nephrotoxicity induced by sodium arsenite (SA). MATERIALS & METHODS: We have used the 35 male Wistar rats in five equal groups (n = 7). Normal saline in (5 ml/kg; p.o.; 21 days) was given to the control group. Sodium arsenite (10 mg/kg; p.o.; 14 days) was given to the SA group. CHR (25, 50 and 100 mg/kg; p.o.; 21 days) and SA (10 mg/kg; p.o.; 14 days from the 7th day of the experiment) was given to the SA + CHR 25, 50 and 100 groups. On the 22nd day of the experiment, the animals' bloods and kidneys were taken, and then we have performed functional, biochemical and histological assessment. RESULTS: CHR pre- and alongside administration (more potently at dose of 100 mg/kg) with SA reduced the SA-induced alterations in serum creatinine and blood urine nitrogen levels. Increased levels of protein carbonyl, myeloperoxidase, malondialdehyde and nitric oxide in kidney tissue were decreased by CHR treatment. CHR administration increased the levels of glutathione and activities of glutathione peroxidase, catalase and superoxide dismutase in renal tissue. Moreover, treatment with CHR reduced the levels of inflammatory mediators including interleukin 1 beta and tumor necrosis factor alpha in renal tissue. The renal histological lesions induced SA were mitigated by CHR treatment in dose dependent manner. CONCLUSION: The results of present study suggested that administration of CHR before and alongside with SA attenuated the renal toxic effects of SA via antioxidative stress and anti-inflammatory effects.

The Effect of Verapamil on TXNIP Gene Expression, GLP1R mRNA, FBS, HbA1c, and Lipid Profile in T2DM Patients Receiving Metformin and Sitagliptin.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes. A decrease in the number of pancreatic beta cells is a pathological sign of diabetes, and to date there is no drug treatment that targets damage to these cells. Pancreatic beta cells have a weak antioxidant system and are highly sensitive to oxidative stress reactions that occur within cells. Thioredoxin interacting protein (TXNIP) inhibits thioredoxin, which is part of the intracellular antioxidant system, thereby accelerating oxidative stress and apoptosis of pancreatic beta cells. Verapamil is a non-dihydropyridine calcium channel blocker. The efficacy of this drug to improve beta cell survival and glucose homeostasis by inhibiting TXNIP expression has been demonstrated in in vitro studies. Although several retrospective studies have shown a lower incidence of T2DM with verapamil treatment, no prospective intervention studies have determined the efficacy of this drug in patients with T2DM. METHODS: The aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and safety of oral verapamil administration in T2DM patients. In this 90-day study, the effects of verapamil on fasting blood sugar (FBS), hemoglobin A1C (HbA1c), and the lipid profile were evaluated and compared with those of the placebo. RESULTS: There was a significant decrease in HbA1c (about 0.5%) in the verapamil group at the end of the intervention period. The effects of verapamil on TXNIP gene expression and glucagon-like peptide-1 receptor (GLP1R) mRNA were compared with those of the placebo (at baseline, after 15 and 30 days, and at the end of the study). During the first month of the study, decreased TXNIP gene expression and increased GLP1R mRNA were associated with the administration of verapamil when compared with the placebo, although the differences were not significant. CONCLUSION: Verapamil can lead to better control of T2DM by reducing TXNIP gene expression and increasing beta cell survival and, possibly, by other mechanisms. CLINICAL TRIAL REGISTRATION: IRCT registration no.: IRCT20180417039339N1 ( https://www.IRCT.ir ).

Experimental Therapeutic Strategies in Epilepsies Using Anti-Seizure Medications.

Epilepsies are among the most common neurological problems. The disease burden in patients with epilepsy is significantly high, and epilepsy has a huge negative impact on patients' quality of life with epilepsy and their families. Anti-seizure medications are the mainstay treatment in patients with epilepsy, and around 70% of patients will ultimately control with a combination of at least two appropriately selected anti-seizure medications. However, in one-third of patients, seizures are resistant to drugs, and other measures will be needed. The primary goal in using experimental therapeutic medication strategies in patients with epilepsy is to prevent recurrent seizures and reduce the rate of traumatic events that may occur during seizures. So far, various treatments using medications have been offered for patients with epilepsies, which have been classified according to the type of epilepsy, the effectiveness of the medications, and the adverse effects. Medications such as Levetiracetam, valproic acid, and lamotrigine are at the forefront of these patients' treatment. Epilepsy surgery, neuro-stimulation, and the ketogenic diet are the main measures in patients with medication-resistant epilepsies. In this paper, we will review the therapeutic approach using anti-seizure medications in patients with epilepsy. However, it should be noted that some of these patients still do not respond to existing treatments; therefore, the limited ability of current therapies has fueled research efforts for the development of novel treatment strategies. Thus, it seems that in addition to surgical measures, we should look for more specific agents that have less adverse events and have a greater effect in stopping seizures.

Zingerone Mitigates Carrageenan-Induced Inflammation Through Antioxidant and Anti-inflammatory Activities.

Inflammation is the body's response against various pathogens and has a critical role in numerous diseases. Zingerone (Zing), a bioactive substance derived from ginger root, has a variety of pharmacological properties, such as reducing inflammation, and antioxidant effects. We aimed to evaluate the beneficial effects of Zing in a carrageenan-induced inflammation model. Paw edema induced by carrageenan (100 µl of 1%) was used to induce acute inflammation in rats. Different doses of Zing (10, 20, and 40 mg/kg) were administered intraperitoneally. Paw tissue levels of MDA, NO, CAT, SOD, GPx, GSH, COX-2, PGE2, TNF-α, and IL-1ß were estimated. Our results showed that Zing, especially at the highest dose of 40 mg/kg, significantly reduced paw swelling in carrageenan-injected animals. Zing significantly increased paw enzymatic and nonenzymatic antioxidants except CAT. It also decreased paw levels of MDA, NO, COX-2, PGE2, TNF-α, and IL-1ß. The results of this study show that Zing may provide an alternative for the clinical control of inflammation through antioxidant and anti-inflammatory activities.

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats by Combination Treatment of Two Natural Phenolic Compounds: Quercetin and Gallic Acid.

The present study aimed to investigate the protective effects of two potent natural antioxidants, gallic acid and quercetin as single or combination treatment against bleomycin-induced pulmonary fibrosis (PF). A total of 50 Wistar rats were randomly divided into 5 groups. Group 1 and 2 intratracheally received saline and bleomycin (7.5 UI/kg), respectively, on day 7, accompanied by oral saline administration for 28 day. Groups 3, 4, and 5 received a single dose of bleomycin on day 7, accompanied by oral administration of gallic acid, quercetin, and their combination, respectively, for 28 day. Finally, the lungs were removed for biochemical and histopathological tests. The combination treatment demonstrated a remarkable decrease in lung hydroxyproline and TNF-α level and increase in catalase activity as compared with both single phytochemical-treated groups. The combination treatment significantly enhanced lung SOD activity and GSH level and decreased NO and IL-6 levels as compared with quercetin-treated group. However, only combination treatment could decrease the lung index and completely reversed histopathological changes in the bleomycin-treated group. In sum, when compared to a single exposure, the combination treatment might be a more effective approach for PF treatment because of its superior efficacy in reversing lung histological changes in the bleomycin-treated group.

Mechanisms involved in the possible protective effect of chrysin against sodium arsenite-induced liver toxicity in rats.

Arsenic as a one of the most important toxic metals could induce hepatotoxicity. Previous reports revealed the significance of oxidative stress in promoting of arsenic-induced liver toxicity. The aim of the present investigation is to evaluate the effect of chrysin (CHR), a natural flavonoid with potent antioxidant activity, against sodium arsenite (SA)-induced hepatotoxicity. Thirty male Wistar rats were divided into four groups: Group 1: received normal saline (2 ml/kg/day, orally for 21 days), Group 2: received SA (10 mg/kg/day, orally for 14 days), Group 3, 4 and 5: received CHR (25, 50 and 100 mg/kg/day, respectively, orally for 21 days) and SA (10 mg/kg/day, orally for 14 days) from the 7th day. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were evaluated. Moreover, liver glutathione peroxidase and myeloperoxidase activity as well as levels of protein carbonylation, malondialdehyde, glutathione, catalase, nitric oxide, superoxide dismutase, tumor necrosis factor-α and interleukin-1ß were evaluated. Moreover, histological evaluation was done. Our results revealed that treatment with CHR (more potentially at the dose of 100 mg/kg/day) before and alongside with SA significantly mitigated the SA-induced hepatotoxicity. Also, the hepatoprotective effect of CHR was verified by the histological evaluation of the liver. The results of current study demonstrated that CHR (100 mg/kg/day) could mitigate the oxidative stress and inflammation induced by SA in liver tissue.

Protective effect of alpha-lipoic acid on di-(2-ethylhexyl) phthalate-induced testicular toxicity in mice.

Phthalates are synthetic chemicals, widely used as plasticizers due to their flexibility in plastics. Human populations may be exposed to phthalates through direct contact or environmental contamination. Most studies have focused on the effects of phthalates on the reproductive tract and have classified these compounds as endocrine disruptors. In this study, we aimed to investigate the possible oxidative damage induced by di-(2-ethylhexyl) phthalate (DEHP) in the mouse testis and to evaluate the regulatory effects of alpha-lipoic acid (LA). For this purpose, forty male mice were divided into four experimental groups. Group I received normal saline (2 mL/kg; p.o.) and corn oil (5 mL/kg; p.o.) as the control group, group II received DEHP (2 g/kg; p.o.), group III received DEHP and LA (20 mg/kg; p.o.), and group IV was treated with LA alone; treatments continued for 2 weeks. The glutathione level (GSH), as well as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities, was determined in mice. In addition, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were measured. Nitric oxide (NO) level, malondialdehyde (MDA) level, sperm characteristics, and histological changes of the testes were also evaluated. The results showed that 2 g/kg of DEHP could significantly decrease the sperm motility. Based on our findings, DEHP significantly reduced the production and count of sperms; these toxic effects were associated with alterations in the serum hormone levels. In the DEHP group, a significant reduction was reported in the serum testosterone, FSH, and LH levels. LA improved DEHP-induced changes in hormonal levels and sperm index. According to our findings, treatment with DEHP triggered histopathological changes and oxidative stress, which were normalized by LA pretreatment. In conclusion, DEHP disrupts the testicular function in rats, at least partly through induction of oxidative stress. On the other hand, LA exhibits potential protective effects on testicular toxicity induced by DEHP.

Crocin: a protective natural antioxidant against pulmonary fibrosis induced by bleomycin.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and fibrotic lung disease of unknown causes. Given the crucial role of oxidative stress in the progression of IPF, antioxidant therapy may be speculated to be an efficient therapeutic approach. Therefore, the present study aimed to evaluate the protective effects of Crocin as a potent, natural antioxidant against Bleomycin-induced PF in male Wistar rats. METHODS: Forty male Wistar rats were randomly divided into four groups. Group 1 received intratracheal saline on day 7 and oral gavage of saline for 28 days. Group 2 received a single dose of Bleomycin on day 7 and oral gavage of saline for 28 days. Groups 3 received a single dose of Bleomycin on day 7, accompanied with oral administration of Crocin for 28 days. Group 4 orally received Crocin for 28 days. Finally, the lungs were removed for measuring the biochemical and histopathological markers. RESULTS: The results showed that Crocin therapy remarkably decreased TNF-α, MDA and NO levels in the lungs of Bleomycin-exposed rats. Furthermore, a significant increase was seen in lung GSH content, catalase, and GPx activities in the Crocin/Bleomycin-treated group as compared with Bleomycin-treated group. However, Crocin could not markedly change the lung index and SOD activity. Histopathological changes, fibrosis and hydroxyproline content of lungs also significantly decreased by Crocin therapy in the Crocin/Bleomycin-treated group. CONCLUSION: In sum, Crocin therapy could modulate biochemical and histological changes induced by Bleomycin; therefore, it might be considered as an effective therapeutic approach against IPF.

Evaluation of oral zinc sulfate effect on obsessive-compulsive disorder: a randomized placebo-controlled clinical trial.

OBJECTIVE: Obsessive-compulsive disorder is a common neuropsychiatric condition. Although various pharmaceutical agents are available for the treatment of obsessive-compulsive disorder, psychiatrists often find that many patients cannot tolerate the side effects of these medications, the patients do not respond properly to the treatment, or the medications lose their effectiveness after a period of treatment. The augmentation with safe supplementation of medication, such as with trace elements, may be a solution to some of these problems. METHODS: This study was a prospective, double-blinded, 8-wk trial. Twelve patients were given fluoxetine (20 mg/d) plus zinc (440 mg/d) and 11 patients were given fluoxetine plus placebo for 8 wk. RESULTS: Both groups showed a decrease in the mean Yale-Brown Obsessive-Compulsive Scale score. Based on t tests, in weeks 2 and 8, patients treated with fluoxetine plus zinc had significantly lower scores than those treated with fluoxetine plus placebo. CONCLUSION: The results show that zinc, as adjuvant agent for obsessive-compulsive disorder, produces improved outcomes.

A Double-Blind, Placebo-Controlled Study of the Aqueous Extract of Echium amoenum for Patients with General Anxiety Disorder.

The aim of this study was to assess the efficacy and tolerability of the aqueous extract of Echium amoenum in combination with SSRIs in patients with General Anxiety Disorder (GAD). The study was an 8-week double-blind randomized clinical trial. Thirty-seven adult outpatients who met the DSM-IV-TR criteria for GAD based on the structured clinical interview participated in the trial. In this study, patients were randomly assigned to receive the aqueous extract (500 mg) plus fluoxetine or fluoxetine (20 mg/day) plus placebo. The results showed significant difference between the two groups in the treatment of GAD. Moreover, there was not any significant difference between the two groups in terms of observed side effects. E. amoenum is effective on anxiety disorder, especially in higher dosage, without any serious side effects.

A preliminary randomized double-blind clinical trial on the efficacy of celecoxib as an adjunct in the treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder is a common neuropsychiatric condition. Although a variety of pharmaceutical agents is available for its treatment, psychiatrists have found that many patients cannot tolerate the side effects, do not respond to treatment adequately, and may finally discontinue their treatment. However, augmentation strategies have been shown to have some benefits in the treatment of OCD. These include reducing both the overall cost of treatment and the side effects. The purpose of this study was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of OCD in an 8-week, double-blind, placebo controlled trial. To this end, 25 patients were assigned to a study group and were given fluoxetine 20mg/day plus celecoxib 400mg/day (200mg BID). The control group included 25 patients who were given fluoxetine 20mg/day plus placebo. Both protocols significantly lowered scores on the Yale-Brown Obsessive-Compulsive Scale over the trial period. The combination of fluoxetine and celecoxib decreased the symptoms of obsessions and compulsions significantly more than fluoxetine plus placebo. The results of this study suggest that celecoxib can be an effective adjuvant agent in the management of patients with OCD; therefore, anti-inflammatory therapies should be further investigated.

A double-blind, placebo-controlled pilot study of ondansetron for patients with obsessive-compulsive disorder.

OBJECTIVE: To assess the efficacy and tolerability of ondansetron in combination with selective serotonin reuptake inhibitors (SSRIs) in patients with obsessive-compulsive disorder (OCD). METHODS: The study was an 8-week pilot double-blind randomized clinical trial. Forty-two adult outpatients who met the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) criteria for OCD based on the structured clinical interview participated in the trial. In this study, patients were randomly assigned to receive either ondansetron (4 mg) plus fluoxetine or fluoxetine (20 mg/day) plus placebo. RESULTS: The results showed a significant difference between two groups in the treatment of OCD (based on t-test). There was not any significant difference between the two groups in terms of observed side effects. CONCLUSIONS: The results of this study show that ondansetron has positive effects on obsession and compulsion which start two weeks after the beginning of the treatment.

Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of Obsessive-Compulsive Disorder.

Obsessive-Compulsive Disorder (OCD) is a common neuropsychiatric condition. Although a variety of pharmaceutical agents is available for the treatment of OCD, psychiatrists often find that many patients cannot tolerate the side effects of these medications; do not respond properly to the treatment; or the medications lose their effectiveness after a period of treatment. Herbal medicine can be a solution to some of these problems. In fact many herbs with psychotropic effects exist which can have fewer side effects. They can provide an alternative treatment or be used to enhance the effectiveness of conventional anti-obsessive and compulsive symptoms. Silybum marianum (L.) Gaertn. is a well-known medicinal plant with a long history of usage in Iran. This plant is reported to be safe on humans. Our objective in this study was to compare the efficacy of the extract of S.marianum (L.) with fluoxetine in the treatment of OCD. The study was an 8-week pilot double-blind randomized trial. Thirty five adult outpatients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial. The minimum score of Yale-Brown Scale for OCD was 21 for all patients. In this double-blind and randomized trial, patients were randomly assigned to receive either capsule of the extract (600 mg/day) or fluoxetine (30 mg/day) for 8 weeks. The results showed no significant difference between the extract and fluoxetine in the treatment of OCD. There was also no significant difference between the two groups in terms of observed side effects.