Original Research article


Hexavalent Chromium Induced Oxidative Stress and Toxicity on isolated human lymphocytes

Enayatollah Seydi, Fatemeh Mahzari, Mohammad Hadi Zarei, Maral Ramazani, Jalal Pourahmad

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e1:1-7
https://doi.org/10.22037/ipa.v3i1.28616

Introduction: The most toxic form of chromium (Cr) in the environment is the oxyanion chromate (Cr (VI)). In this form it is soluble and is transported into the cells. Chromate structurally resemble phosphate and sulfate, and can be transported into cells by the anion carrier.

 Methods and Results: In this study, toxicity effects of Cr (VI) on isolated human lymphocytes was studied using accelerated cytotoxicity mechanisms screening (ACMS) technique. Human lymphocytes were isolated from blood of healthy persons using Ficoll-paque PLUS standard method. The trypan blue dye was used to cytotoxicity assay. The mechanistic parameters including reactive oxygen species (ROS), lysosomal membrane destabilization, mitochondrial membrane potential (MMP) collapse, lipid peroxidation, GSH and GSSG levels were assessed after 1, 2 and 3 hrs in potassium dichromate treated lymphocytes. The results indicate that toxicity of Cr (VI) was concentration dependent in human lymphocytes. Cr (VI) significantly (p<0.05) induced ROS production, MMP reduction, lysosomal membrane destabilization and lipid peroxidation in human lymphocytes. There was also a decrease in intracellular GSH and raise in extracellular GSSG levels in Cr (VI) treated lymphocytes.

 Conclusion: OOur findings revealed that ROS formation with subsequent cellular damages is the molecular mechanism for Cr (VI) induced human blood lymphocyte toxicity.

The Use of Nata de Coco Derived Bacterial Cellulose as a Potential Excipient for Directly Compressed Tablets

Shariza Sahudin, Mumtaz Hussain, Shaharizuan Abd Rahman, Muhammad Aliff Shahkirin Hamdan, Muhamad Rizal Abd Rahim

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e2:1-5
https://doi.org/10.22037/ipa.v3i1.29058

Introduction: Nata de coco is produced through the fermentation of coconut water using Acetobacter xylinum bacteria. Nata de coco is chemically high in fiber, consisting of bacteria-derived cellulose. Bacterial celluloses present a number of unique physical properties compared to plant celluloses including a relatively high purity and crystallinity, with mechanical strength. These properties lend Nata de coco to be extremely amenable to research.

Methods and Results: The current study attempts to assess the suitability of Nata de Coco derived bacterial cellulose in direct compression tablet formulation. Nata de coco, at various states of hydration, defined here as 0%, ‘low’ and ‘high’, achieved by both oven-drying and freeze-drying is incorporated into a low-dose loratadine powder blend for direct compression into tablets. The dissolution profile of these novel tablets was evaluated for release properties. The resulting tablets reveal freeze-drying, compared with oven-drying, markedly improve the properties of Nata de Coco for inclusion in a tablet formulation, producing tablets with improved disintegration times and dissolution profiles and retaining physical stability. Ovendried Nata de Coco, resulting in physically weaker tablets, with poor friability and hardness. The upper limit for water-content in both cases, similar to HPMC, appears to be 11%.

Conclusions: Freeze-dried Nata de Coco, therefore presents considerable promise for use as a tablet excipient to produce a rapid-release formulation.

Effects of erythromycin, nystatin and their combination on Pseudomonas aeruginosa and Candida albicans biofilms

Umi Marshida Abd Hamid, Siti Fadhilah Mohd Isa , Mohd Fakharul Zaman Raja Yahya

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e3:1-8
https://doi.org/10.22037/ipa.v3i1.31304

Introduction: Pseudomonas aeruginosa is frequently found to coexist and interact with Candida albicans in the polymicrobial biofilms. Considering the pathogenicity of polymicrobial biofilms in many persistent infections, this study was aimed to evaluate the combined effects of antibiotics erythromycin and nystatin on P. aeruginosa-C. albicans polymicrobial biofilm under both aerobic and anaerobic conditions.

Methods and Results:

Treatment with single (erythromycin or nystatin) and combined antibiotics caused subtle reductions in the number of viable biofilm cells as well as protein and extracellular DNA content of the biofilm extracellular polymeric substance (EPS). Protein profiling demonstrated differential expression of biofilm proteins following exposure to the antimicrobial treatments.

Conclusion: These findings suggest that erythromycin and nystatin, either single or in combination affect EPS composition (protein and extracellular DNA) as well as biofilm protein expression.

Reformulation of Le’Natura® Biscuit: Effects on Textural, Sensorial, Nutritional and Glycemic Index Values

Bujang Aishah, Jailani Fadhilah, Abdullah Noriham, Ahmad Noorlaila, Likan Aisyah Jacklin, Faizul Effendi Yun Irma

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e4:1-5
https://doi.org/10.22037/ipa.v3i1.31577

Introduction: The purpose of this study was to reformulate Le’Natura® biscuit for textural, sensorial, nutritional and glycemic index properties improvement. The original biscuit had a brittle and coarse texture with a bitter after-taste. It also contained high carbohydrate which made the biscuit unsuitable for diabetic patients and less desirable to the health-conscious consumers.

Methods and Results: Several ingredients from the original formulation were either eliminated, reduced or substituted in order to modify the texture and taste, to obtain a low glycemic index (GI) value and to increase acceptability. The ingredients involved in reformulation were wheat flour, milk powder, maltodextrin, atta flour, green bean flour, polydextrose, palm oil, and leavening agents. The final reformulated biscuit showed improvements in thickness, spread ratio, fracturability and firmness properties. The improved biscuit also scored higher acceptability for appearance, texture, sweetness, after-taste and overall acceptability attributes. The in vivo GI measured indicates that the improved biscuit was in the low GI range of 44.7±4.7 compared to the original biscuit (63.5±7.7, moderate GI). The nutrients composition of total energy, fat, protein, dietary fiber, iron, and calcium content were increased while total carbohydrate and sodium levels were decreased.

Conclusions: With the improvements, Le’Natura® biscuit is expected to capture the functional food market segment more competitively.

Keywords: functional food; biscuit; glycemic index; high fiber

Homometallic Dinuclear Cu(II) and Zn(II) Complexes Derived from Salophen-type Ligand: Synthesis, Characterization and Anticancer Screening

Siti Solihah Khaidir, Hadariah Bahron, Amalina Mohd Tajuddin, Kalavathy Ramasamy

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e5:1-6
https://doi.org/10.22037/ipa.v3i1.31911

Introduction:

A series of salophen-type Cu(II) and Zn(II) dinuclear metal complexes of a Schiff base derived from o-phenylenediamine were successfully synthesized, characterized and screened for their anticancer activity.

Methods and Results:

All compounds were characterized physicochemical and spectral techniques namely elemental analysis (C, H, N), magnetic susceptibility (MSB), molar conductivity, thermal gravimetric analysis (TGA), infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The shifting of C=N, C-O phenolic and C-O methoxy peaks and the appearance of new peaks assignable to M-N and M-O in IR spectra of the complexes indicated the coordination of azomethine N, phenolic O and methoxy O donor atoms with metal centers. The disappearance of the hydroxyl peak in 1H NMR spectra of the Zn(II) complex supported the involvement of phenolic O upon formation of the metal complex. The Cu(II) complex was paramagnetic with magnetic moment values of 1.97, close to the theoretical spin only magnetic moment, μso, for Cu(II). The compounds were screened for anticancer activity against human colon cancer cells (HCT116). The Cu(II) complex revealed the highest activity with IC50 value of 21.17 ± 0.76 μM.

Conclusion:

The ligand coordinated as a hexadentate ligand through O and N donor atoms of phenolic, methoxy and azomethine groups. From anticancer screening, it was observed that Cu2(OVanOPD) complex exhibited the highest activity followed by OVanOPD ligand and Zn2(OVanOPD) complex.

Antioxidant and chemopreventive effects of Asperugo procumbens in a rat model of hepatocellular carcinoma

Mahdieh Arabsalmani, Mahsa Hosni, Farshad H Shirazi, Sina Andalib, Saman Gholami, Seyed Hojjat Hosseini, Mohammad Kamalinejad, Maryam Noubarani, Mohadeseh Shamseini, Mohammad Reza Eskandari

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e6:1-6
https://doi.org/10.22037/ipa.v3i1.24879

Introduction: Hepatocellular carcinoma (HCC) cancer is the fifth most common malignancy, with 0.25–1 million new cases diagnosed annually worldwide. The objective of the present study was to evaluate the antioxidant and chemopreventive effects of aqueous extract of Asperugo procumbens L. (AAP) against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats.

Methods and Results: The model of hepatocellular carcinoma was induced by a single intraperitoneal injection of DEN (200 mg/kg) as an initiator that after two weeks followed by daily oral administration of 2-acetylaminofluorene (30 mg/kg) as a promoter for two weeks.

AAP-treated rats were pretreated with the extract intragastrically at three different doses two weeks prior to DEN injection. At the end of the experiment, the marked reduction of serum biomarkers of liver damage and cancer, including alfa-fetoprotein (AFP), gamma glutamyl transpeptidase (GGT), alanine transaminase (ALT), and aspartate transaminase (AST) were observed in AAP complemented rats as compared to DEN-treated animals. Besides, the extract exhibited in vivo antioxidant activity that evident by increasing GSH concentration along with lipid peroxidation prevention in the liver tissues of HCC animals. In addition, A. procumbens showed in vitro free radical scavenging activity that determined by 1, 1-Diphenyl-2-picryl hydroxyl (DPPH) antioxidant assay. The relative weight of liver was also reduced in AAP-treaded rats as a prognostic marker in HCC.

Conclusions: Our results obviously confirmed that A. procumbens possesses a chemopreventive effect against primary liver cancer induced by DEN in rats as well as  in vitro and in vivo antioxidant activities.

The Clozapine-induced Toxicity via Induction of Oxidative Stress and Mitochondrial Dysfunction in Human Blood Lymphocytes and Protecting role of L-Carnitine

Jalal Pourahmad, Ahmad Salimi, Farnaz Imani, Zhaleh Jamali, Negar Ahvar

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e9:1-9
https://doi.org/10.22037/ipa.v3i1.32179

Clozapine is a useful antipsychotic drug but with serious, life threatening toxicity effects. The aim of this study is to assess the direct cytotoxicity effect of clozapine (CLZ) on human blood lymphocytes and investigate the protective effect of L‐carnitine (LC) against clozapine‐induced cytotoxicity. Clozapine at 70 μM concentration induced cytotoxicity following 12 h. The Clozapine induced cytotoxicity was associated with intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione (GSH) and raising of oxidized glutathione (GSSG). We showed that LC (1 mM) has a beneficial cytoprotective effect against clozapine-induced toxicity. Summery, clozapine causes organelles damages and triggers oxidative stress in lymphocytes. These data suggest that using of L‐carnitine could be useful for prevention and treatment of clozapine toxicity. Finally, it could be concluded that LC exerts a beneficial antioxidant and mitochondrial protective effects against oxidative stress induced by CLZ.

Measurement solubility of Acetylsalicylic Acid in water and alcohols

Amir Hosein Ostadhashem, Kiana Peyvandi

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e11:1-7
https://doi.org/10.22037/ipa.v3i1.32231

Low aqueous solubility of drug is one of the problems in pharmaceutical industry and the enhancement of the solubility of these poorly soluble drugs has recently attracted the consideration of researchers. In this way, one of the essential methods to overcome this challenge is to use co-solvents. In this study, a set of experiments was conducted to measure the solubility and density of Acetylsalicylic Acid as a painkiller drug in water, 1-octanol, ethanol, methanol, and ethylene glycol as solvents in the temperature range of 298 to 330 K. Furthermore, the experiments are carried out at 298K in the binary mixture of solvents to investigate the interaction effect of another solvent or anti-solvent in different percentages of mixtures. The results of this investigation revealed that using binary solution of water and ethanol, as a solvent aid, was able to increase the solubility especially in high percentage of ethanol. Moreover, to indicate the applicability of simple empirical model, the experimental data was used to optimize two adjustable parameters of the selected model. In future research, a successful thermodynamic models will be offered based on gathered data for prediction of solubility in the different temperature with high accuracy. 

Brief Communication and Method report


Analysis of essential oil from leaves and Bulb of Allium atroviolaceum

Parniyan Sebtosheikh, Mahnaz Qomi, Shima Ghadami, Faraz Mojab

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e8:1-6
https://doi.org/10.22037/ipa.v3i1.32106

Background and objective: Medicinal plants used in traditional medicine as prevention and treatment of disease and illness or use in foods, has a long history. Plants belonging to genera Allium have widely been acquired as food and medicine. In many countries, including Iran, a variety of species of the genus Allium such as garlic, onions, leeks, shallots, etc use for food and medicinal uses. Method: The leaves and bulbs of Allium atroviolaceum, collected from Borujerd (Lorestan Province, Iran) in May 2015 and their essential oils of were obtained by hydro-distillation. The oils were analyzed by gas chromatography coupled with mass spectrometry (GC/MS) and their chemical composition was identified. Results: The major constituents of A. atroviolaceum leaves oil were dimethyl trisulfide (59.0%), ethyl linolenate (12.4%), phytol (11.4%) and in bulb oil were methyl methyl thiomethyl disulfide (61.3%), dimethyl trisulfide (15.1%) and methyl allyl disulfide (4.3%). The major constituents of both essential oils are sulfur compounds. Conclusion: The results of the present study can help to increase of our information about composition of an edible herb in Iran. The major components of the oils can use as marker for standardization of the herbs.

Case report


Unexpected Treatment in a Severe Covid-19 Patient with Essential Thrombocythemia Who Received Oseltamivir and Hydroxychloroquine

Haleh Talaie, Maryam Nazari, Sayed Masoud Hosseini, Helia Ghanean

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e7:1-4
https://doi.org/10.22037/ipa.v3i1.31833

Introduction: Novel coronavirus disease (Covid-19) has been recognized as a new human infectious disease caused by a mutated type of coronavirus that might be associated with thrombocytopenia through different mechanisms. Moreover, the presence of underlying disease is a risk of hospitalization and poor prognosis of Covid-19.

Case report: Here, we describe a 77-year-old male Covid-19 patient with essential thrombocythemia. Although gastrointestinal symptoms (GI) were uncommon in the early stages of the pandemic, he presented to a clinic with GI symptoms and general weakness. He didn't have any respiratory involvement and laboratory tests revealed a hemoglobin and platelet reduction (810000/micL to 174000/micL), leukopenia, and elevated D-dimer. He received oseltamivir (75 mg twice daily) and hydroxychloroquine (200 mg twice daily) for five days.

Discussion & Conclusions: Despite his underlying disease and severity of illness including one-month fever, malaise, and a weight loss of 11 kg in ten days, he was cured without any hospitalization.

Systematic Review and Meta Analysis


The Impact of Current COVID-19 Therapeutics on Patients’ Clinical Improvements Based on Disease Severity; A Systematic Review.

Haleh Talaie, Maryam Nazari, Sayed Masoud Hosseini, Atieh Mousavizadeh, Ilad Alavi-Darazam, Hossein Vatanpour

International Pharmacy Acta, Vol. 3 No. 1 (2020), 14 December 2020, Page 3e10:1-16
https://doi.org/10.22037/ipa.v3i1.32431

Introduction: COVID-19 pandemic is not a new issue that encompasses the entire world. It is becoming increasingly urgent to find effective medications. This systematic review was conducted to discuss the clinical impact of some proposed managements against COVID-19.

Methods: PubMed, Scopus, Cochrane Library, Embase, and Google Scholar databases were searched from their inception to June 15, 2020, to identify studies reporting the current treatment process and medications for COVID-19.

Results: After searching databases, a total of 5450 articles were assessed. A number of 42 relevant studies were identified as eligible for the review including a total of 5599 patients. The severity of illness was investigated in 5053 cases including 3169 mild or mild to moderate or moderate, 222 moderate to severe, and 1662 severe cases. Among the therapeutics reported in these studies, 15 medications besides convalescent plasma showed some evidence of antiviral activity. Antivirals (34%; 14/42), especially lopinavir/ritonavir, were the main classes of therapeutic agents evaluated against COVID-19. Approximately, 14.3% (6/42) of the studies which assessed the impact of hydroxychloroquine and azithromycin, convalescent plasma therapy, lopinavir/ritonavir plus azithromycin, methylprednisolone, and interferon α-2b, have reported clinical improvement in all cases. A number of 10 studies (23.81%) exhibited a negative conversion of SARS-CoV-2 in all cases.

Conclusions: Based on our findings, considering the diverse and scattered effects of current medications on clinical outcomes and the rate of negative conversion of SARS-CoV-2, large clinical trials are required to evaluate the best treatment options for COVID-19.