The effect of acidic beverage versus mineral water on the change in serum phenobarbital concentrations: a randomized clinical trial on children with seizure.

OBJECTIVE: To assess the effect of an acidic beverage (Orange juice) on the change in serum Phenobarbital concentrations in children with seizure who take Phenobarbital as the main treatment. METHODS: We did a parallel design and placebo controlled randomized clinical trial. Patients attending Heshmatiyeh Hospital (Iran) were recruited from October 2016 to December 2017. Forty patients randomly assigned to either experimental group or control group. Firstly, 5 mL blood sample was taken from both groups to measure serum Phenobarbital concentration before experiment. Then, one oral dose of Phenobarbital (2.5 mg/kg) with 100 mL of corporate Orange juice (pH = 3.5) (experiment group) or 100 mL of mineral water (neutral pH) (control group) was given to each group, respectively. After 2 h of administration, another blood sample was taken. The high-performance liquid chromatographic system was used for measurement of serum Phenobarbital concentration. RESULTS: There was significant increase in serum Phenobarbital concentrations after taking Phenobarbital in experiment group in comparison to control group. Statistical analysis revealed a significant increase in change of serum Phenobarbital concentrations in experiment group versus control group. CONCLUSION: The results of the current trial indicate that the level of serum Phenobarbital in the experiment group was higher than that of control group.

Toxicology of long-term and high-dose administration of methylphenidate on the kidney tissue - a histopathology and molecular study.

The present study aims to assess the influences of oral methylphenidate on kidney function and structure versus vehicle treatment in adult male rats. In this study, thirty adult male rats equally into two treatment groups divided randomly, and among them, MPH has been administered for 21 days, at doses of 20 mg/kg, and the control group has received salin. In renal, under the effect of MPH applying quantitative real-time PCR, we analyzed nephrotoxicity-related molecular pathways like autophagy, inflammation, and apoptosis. Moreover, the levels of GSH, CAT, and SOD were investigated as antioxidant enzymes. Afterward, stereological analysis in MPH-treated rats has been performed. Analysis of qPCR displayed inflammation, impaired autophagy, and enhanced apoptosis with histological changes in the kidney's tissue, also an important rise in the antioxidant enzymes' level. Besides, 20 mg/kg of MPH led to a decline in the mean of Bowman's space thickness and renal corpuscle's volume in comparison to the control rats. Collectively, our histological and molecular data implicit that in the kidney region, administrating of MPH evoked discriminative expression alterations in nephrotoxicity-associated signaling cascades, specifically autophagy, inflammation, and apoptosis paired with important damage to kidney tissue.

Effects of glucosamine against morphine-induced antinociceptive tolerance and dependence in mice.

BACKGROUND: The most important limitations of morphine in pain therapy are its tolerance and dependence. In this study, we evaluated the protective effect of glucosamine against morphine-induced tolerance and dependence in mice. METHODS: Mice received twice daily morphine (20 mg/kg, s.c.) alone, or along with orally administered glucosamine (500, 1000 and 2000 mg/kg), for 9 continuous days. To assess antinociceptive effect of morphine, percentage of maximal possible effect (%MPE) of animals exposed to thermal stimulus was measured in the hot plate test, 30 min after morphine administration. Test was performed on days 1, 3, 5, 7 and 9. The effect of glucosamine on the naloxone (5 mg/kg, i.p.)-precipitated morphine withdrawal, was also evaluated. Changes in brain gene expression levels of induced nitric oxide synthase (iNOS), enzyme responsible for nitric oxide generation, as well as pro-inflammatory mediator, tumor necrosis alpha (TNF-α) were measured in morphine tolerated animals, as well as after withdrawal by real-time polymerase chain reaction (RT-PCR). Protein content of TNF-α was evaluated via ELISA assay. RESULTS: Tolerance to antinociceptive effect of morphine was developed after 7 days of morphine treatment. The concurrent administration of glucosamine (500, 1000 and 2000 mg/kg) with morphine, significantly inhibited tolerance development, on days 7 and 9. In addition, glucosamine ameliorated the naloxone-precipitated opioid withdrawal symptoms (tremor, jumping, teeth chattering, grooming). However, diarrhea was significantly improved only with the dose of 500 mg/kg. Increased mRNA expression of iNOS as well as TNF-α mRNA expression and protein, after both morphine tolerance and withdrawal, were considerably reduced by glucosamine (1000 mg/kg) in the morphine withdrawal animals. CONCLUSION: These data support the utility of glucosamine in attenuating both tolerance to nociceptive effects of morphine as well as withdrawal-induced behavioral profile. Anti-oxidant and anti-inflammatory effects are responsible, at least in part, for the protective effects of this drug.

Toxicity assessment of Ferula gummosa administration during pregnancy, lactation, and juvenile period in rat.

Ferula gummosa is widely used in traditional medicine to treat a variety of ailments. This work evaluated the safety of F. gummosa root in pregnancy, lactation, and juvenile periods. This study was performed in three parts: (1) pregnant rats were received diet containing 0 (control), 150 , or 700 mg/kg of F. gummosa root during pregnancy; (2) Lactating rats were treated with diet containing the root (0, 150, or 700 mg/kg) during lactation period; (3) juvenile rats were received 4 weeks diet containing the root (0, 150, or 700 mg/kg). F. gummosa at both doses had no significant effects on the duration of pregnancy, maternal weight, and the number of delivered pups, but at dose of 700 mg/kg decreased birthweight of the pups. In lactation period, F. gummosa had no significant effects on mortality, body weight, body length, the weight of organs, and blood biochemical parameters of offspring. In juvenile rats, food consumption, body weight, and WBCs number were decreased in treated groups. No histopathological lesions were detected in the brain, heart, liver, lungs and kidney of offspring, and juvenile rats in treated groups. LC/MS/MS analysis confirmed systemic absorption of active constituents of the root by the oral route of administration. In conclusion, F. gummosa root did not produce significant toxic effects during pregnancy, lactation, and juvenile period. But, decrease in birthweight of delivered pups and in weight gain of juvenile rats should be considered in the long-term consumption of this plant.

PROTECTIVE EFFECT OF LACTUCA SERRIOLA ON DOXORUBICIN-INDUCED TOXICITY IN H9C2 CELLS.

The use of doxorubicin (DOX) is limited by its dose-dependency because of its cardiotoxicity. Reactive oxygen species (ROS) play an important role in the pathological process. The aim of this study is to evaluate the protective effect of Lactuca seniola against DOX-induced apoptosis and death in H9C2 cells. The cells were incubated with different concentrations of extract for 4 h which continued in the presence or absence of 5 µM doxorubicin for 24 h. Cell viability, apoptotic induction and the level of apoptotic proteins were determined by using MTT, PI and immunoblotting assays, respectively. The level of lipid peroxidation was measured by fluorimetric method. DOX significantly decreased cell viability which was accompanied by an increase in ROS production and lipid peroxidation. Pretreatment with Lactuca seniola increased the viability of cardiomyocytes and could decrease lipid peroxidation. Also, Lactuca seriola inhibited the reduction of anti-apoptotic Bcl-2 protein and elevation of apoptotic Bax and caspase-3 proteins. In conclusion, Lactuca seniola exerts protective effect against oxidative stress-induced cardiomyocytes damage. Therefore, it has the potential to be used as cardioprotective agent by the patients with cardiovascular diseases.

Different effects of adenylyl cyclase activators and phosphodiesterases inhibitors on cervical cancer (HeLa) and breast cancer (MCF-7) cells proliferation.

Breast and cervical cancers are the most common cancers in Iran and worldwide. Hormonal stimulation of cyclic adenosine mono phosphate (cAMP) and the cAMP-dependent protein kinase PKA regulates cell growth by different mechanism. cAMP can stimulate cell growth in many cell types while inhibiting cell growth in others. In some cell lines have been shown that the proliferation of tumor cells is reduced by increasing cAMP in cells. In this study, we evaluate growth arrest of selective PDE3 and non-selective PDE inhibitors, which lead to increase level of cAMP in cervical (HeLa) and breast cancer (MCF7) cell lines have been studied. Cells were incubated with different concentrations of selective, non-selective PDE inhibitors, beta adrenergic receptor agonist and direct stimulator of adenylyl cyclase. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Result showed that selective PDE inhibitors decreased cell viability in HeLa and MCF-7 cells as a time-dependent manner. Non-selective inhibitor and beta-adrenergic receptor agonist also decrease cell viability but they are less powerful than selective PDE3 inhibitors. Forskolin had no effect in viability of cells. Analysis of DNA fragmentation by flow cytometry showed apoptosis involved in selective PDE3 inhibitors induced toxicity in HeLa cell. Thus, the growth inhibitory effects of selective PDE3 inhibitors are more effective than non-selective inhibitor. Further studies are needed to investigate the mechanism of action is on the field.

A review of the protective effects of quercetin-rich natural compounds for treating ischemia-reperfusion injury.

Ischemia-reperfusion (IR) injury causes dysfunction of tissues and organs, and oxidative stress plays an important role. During IR, reactive oxygen species (ROS) are increased. Antioxidants are used to decrease ROS associated with IR. We review the protective effects of quercetin-rich natural antioxidants against IR. We searched PubMed, ScienceDirect, Scopus and Cochrane databases using the keywords: ischemic reperfusion, quercetin, antioxidant and herbal medicine. The effects of quercetin during IR have been reported for animal models in vitro and in vivo. Quercetin-rich plants including Abelmoschus esculentus, coriander, Hypericum perforatum, onion, Psidium guajava, buckwheat and Rosa laevigata Michx have been used to reduce oxidative stress damage to various organs during IR.

Effects of curcumin nanoparticle on the histological changes and apoptotic factors expression in testis tissue after methylphenidate administration in rats.

The present article sought to evaluate the impact of curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) on the histological variables and apoptotic agents in adult male rats after 3-weeks of methylphenidate (MPH) oral administration (20 mg/kg) versus vehicle therapy on the testis. Twenty-four male rats have been categorized randomly into four groups, in which Group 1 has been chosen as the controls, and Group 2 has been a vehicle and taken the sesame oil as curcumin carrier. Moreover, Group 3 has been taken MPH (20 mg/kg by gavage for 21 consecutive days). Group 4 received MPH plus Curcumin nanoparticles (5.4 mg/100 g) for twenty-one consecutive days. Then, testis histology, apoptosis as well as stereology have been examined. According to the examinations, curcumin nanoparticles are significantly capable of improving the sperms and stereological variables; for example, round spermatid and Leydig cells by enhancing the level of the serum testosterone in comparison with the MPH and vehicle groups. Besides, it was found that the gene expression in inflammation pathways and apoptosis genes largely diminished in the treatment group by curcumin nanoparticles in comparison with the MPH and vehicle groups, also we observed considerable differences for the weight of testes between the examined groups. Therefore, Curcumin effectively inhibited the testis damages and MPH-induced apoptosis, indicating possible protecting features of the Curcumin nanoparticles in opposition to MPH.

HPLC phenolic profile and induction of apoptosis by Linum usitatissimum extract in LNCaP cells by caspase3 and Bax pathways.

Linum usitatissimum is a candidate as a remedy to treat prostate problems in some folklore medicines. In this study, we have reported the phenolic and flavonoid constituents, antioxidant activity, and potential of the plant extract against prostate cancer cells. The phenolic and flavonoid compound profile of the extract were established using HPLC analysis. While the total phenolic and flavonoid content (TPC and TFC) were analyzed using classic methods. The antioxidant activity of the extract was also evaluated. MTT assay and flow cytometry technique was used to evaluate antiproliferation activity and induction apoptosis of the plant extract on prostate cancer cells of LNCaP. We also evaluated the gene expression of Bax and caspase-3 using the real-time qPCR assay. HPLC result revealed that L. usitatissimum extract (LUE) was rich in phenolic acids such as gallic, ferulic, and vanillic acid with the amount of 3.56, 2.12, 1.24 µg/g extract respectively. 383.4 mg GAE/g and 47.1 mgRuE/g were calculated for total phenolic and flavonoid content. LUE exhibited radical scavenging activity with IC50 = 19.3 ± 1.1 µg/mL. LUE chelated ferrous ions with IC50 = 121.1 ± 1.3 µg/mL. LUE showed anti-proliferative activity on LNCaP cells with the IC50 values of 8.3, 6.3, and 5.4 µg/mL after 24, 48, and 72 h treatment. LUE also increased cell mortality by inducing apoptosis (15.3-29.8%). The real-time qPCR results exhibited an increase in gene expression of Bax and caspase-3. Our in vitro study demonstrates that L. usitatissimum can be considered as an effective agent to inhibit the growth and invasion the human prostate cancer cells.

Effect of Boswellia species on the metabolic syndrome: A review.

The metabolic syndrome, a cluster of metabolic disorders, includes abdominal obesity, hypertension, dyslipidemia, and hyperglycemia leading to insulin resistance, development of diabetes mellitus, and cardiovascular diseases. For the treatment of metabolic syndrome, traditional herbal medicines such as frankincense or Boswellia species have been used due to their anti-inflammatory, anti-oxidant, anti-obesity, antidiabetic, antihypertensive, and hypolipidemic properties. Based on the literature, published evidence up to 2020 about the therapeutic effects of Boswellia species on the metabolic disorder among Medline, Scopus, and Google Scholar were precisely evaluated by keywords such as obesity, diabetes, hyperglycemia, hypertension, blood pressure, dyslipidemia, metabolic syndrome, frankincense, and Boswellia. According to the results, Boswellia species have beneficial effects to control metabolic syndrome and its related disorders such as hyperglycemia, dyslipidemia, hypertension, obesity, diabetes, and its complications. Boswellia species by reducing the resistance to insulin and restoring pancreatic beta cells decrease blood glucose. Also, Boswellia species has antithrombotic and anticoagulant properties that regulate blood pressure. The anti-oxidant properties of Boswellia species modulate the blood lipid profile via reducing TNF-α, IL-1ß levels, and increasing the adiponectin level. The therapeutic and protective effects of Boswellia species on metabolic disorders were remarkably confirmed regarding decreasing hyperglycemia, hyperlipidemia, hypertension, and obesity.

Medicinal plants in treatment of hypertriglyceridemia: A review based on their mechanisms and effectiveness.

BACKGROUND: Hypertriglyceridemia (HTg) defines as high amounts of triglyceride (TG) in the blood which can lead to serious complications over time. HTg is usually a part of metabolic disorders such as diabetes mellitus, metabolic syndrome, and dyslipidemia. Different medications have been used to treat HTg but experimentally, many herbs have been recommended for treating HTg as an adjuvant therapy. In most cases, the recommendations are based on animal studies and limited evidences exist about their mechanisms and clinical usefulness. PURPOSE: This review focused on the herbs which have been shown TG lowering effect. METHOD: The search was done in PubMed, Science Direct, Scopus, Web of Science and Google Scholar databases a 20-year period between 1997 to 2017 with keywords search of medicinal plant, plant extract, hypertriglyceridemia, dyslipidemia, hyperlipidemia, lipoprotein lipase and apolipoprotein. RESULTS: According to the results, many plants showed positive effects but Allium sativum, Nigella sativa, Curcuma longa, Anethum graveolens and Commiphora mukul had the best TG lowering effect with exact mechanisms of action. CONCLUSION: It seems that use of these plants as complementary therapeutics or extraction of their active ingredients along with currently available drugs will improve the management of HTg in patients.

Ctotoxic and apoptogenic effects of Perovskia abrotanoides flower extract on MCF-7 and HeLa cell lines.

OBJECTIVE: Perovskia abrotanoides Karel, belongs to the family Lamiaceae and grows wild alongside the mountainous roads inarid and cold climate of Northern Iran. The anti-tumor activity of P. abrotanoides root extract has been shown previously. This study was designed to examine in vitro anti-proliferative and pro-apoptotic effects of flower extract of P. abrotanoides on MCF-7 and Hela cell lines. MATERIALS AND METHODS: Cells were cultured in DMEM medium with 10% fetal bovine serum, 100 units/ml penicillin and 100 µg/ml streptomycin and incubated with different concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic cells were determined using propidium iodide (PI) staining of DNA fragmentation by flow cytometry (sub-G1 peak). RESULTS: P. abrotanoides extract inhibited the growth of malignant cells in a time and dose-dependent manner and 1000 µg/ml of extract following 48h of incubation was the most cytotoxic dose against Hela cell in comparison with other doses; however, in MCF-7 cells,1000 and 500 µg/ml PA induced toxicity at all time points but with different features.. Analysis of flowcytometry histogram of treated cells compared with control cells indicated that the cytotoxic effect is partly due toapoptosis induction. CONCLUSION: Hydro-alcoholic extract of P. abrotanoides flowers inhibits the growth of MCF-7 and HeLa cell lines, partly via inducing apoptosis. Their inhibitory effect was increased in a time and dose-dependent manner, especially in MCF7 cells. However, further studies are needed to reveal the mechanisms of P. abrotanoides extract-induced cell death.