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Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects

Research Abstract
Avermectins are a group of drugs that occurs naturally as a product of fermenting Streptomyces avermitilis, an actinomycetes, isolated from the soil. Eight different structures, including ivermectin, abamectin, doramectin, eprinomectin, moxidectin, and selamectin, were isolated and divided into four major components (A1a, A2a, B1a and B2a) and four minor components (A1b, A2b, B1b, and B2b). Avermectins are generally used as a pesticide for the treatment of pests and parasitic worms as a result of their anthelmintic and insecticidal properties. Additionally, they possess anticancer, anti-diabetic, antiviral, antifungal, and are used for treatment of several metabolic disorders. Avermectin generally works by preventing the transmission of electrical impulse in the muscle and nerves of invertebrates, by amplifying the glutamate effects on the invertebrates-specific gated chloride channel. Avermectin has unwanted effects or reactions, especially when administered indiscriminately, which include respiratory failure, hypotension, and coma. The current review examines the mechanism of actions, biosynthesis, safety, pharmacokinetics, biological toxicity and activities of avermectins.
Research Authors
Gaber El-Saber Batiha , Ali Alqahtani , Omotayo B. Ilesanmi , Abdullah A. Saati , Amany El-Mleeh , Helal F. Hetta and Amany Magdy Beshbishy
Research Journal
Pharmaceuticals
Research Member
Research Pages
196
Research Publisher
MDPI
Research Rank
1
Research Vol
13
Research Website
https://www.mdpi.com/1424-8247/13/8/196/htm
Research Year
2020

Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway

Research Abstract
The search for new and better antimicrobial therapy is a continuous effort. Quercetin is a polyphenol with promising antimicrobial properties. However, the understanding of its antimicrobial mechanism is limited. In this study, we investigated the biochemical mechanistic action of quercetin as an antibacterial compound. Isolates of Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus were initially exposed to quercetin for antibacterial evaluation. Subsequently, S. aureus (Gram-positive) and E. coli (Gram-negative) cells were exposed to quercetin with or without ascorbic acid, and cells were harvested for selected biochemical assays. These assays included redox homeostasis (lipid peroxidation, total thiol, total antioxidant capacity), nitric oxide, and kynurenine concentration as well as DNA fragmentation. The results revealed that quercetin caused lipid peroxidation in the bacterial isolates. Lipid peroxidation may indicate ensuing oxidative stress resulting from quercetin treatment. Furthermore, tryptophan degradation to kynurenine was activated by quercetin in S. aureus but not in E. coli, suggesting that local L-tryptophan concentration might become limiting for bacterial growth. These findings, considered together, may indicate that quercetin restricts bacterial growth by promoting oxidative cellular stress, as well as by reducing the local L-tryptophan availability by activating the kynurenine pathway, thus contributing to our understanding of the molecular mechanism of the antimicrobial action of quercetin.
Research Authors
Oluyomi Stephen Adeyemi 1,* , Chinemerem Ebugosi 1, Oghenerobor Benjamin Akpor 2 , Helal F. Hetta 3,4 , Sarah Al-Rashed 5, David Adeiza Otohinoyi 6, Damilare Rotimi 1 , Akinyomade Owolabi 2 , Ikponmwosa Owen Evbuomwan 2 and Gaber El-Saber Batiha 7
Research Journal
Biology
Research Member
Research Pages
219
Research Publisher
MDPI
Research Rank
1
Research Vol
9
Research Website
https://www.mdpi.com/2079-7737/9/8/219/htm
Research Year
2020

Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase
of Trypanosoma brucei

Research Abstract
The aim of this study was to explore the inhibitory potential of apoferritin or apoferritin-capped metal nanoparticles (silver, gold and platinum) against Trypanosoma brucei arginine kinase. The arginine kinase activity was determined in the presence and absence of apoferritin or apoferritin-capped metal nanoparticles. In addition, kinetic parameters and relative inhibition of enzyme activity were estimated. Apoferritin or apoferritin-capped metal nanoparticles’ interaction with arginine kinase of T. brucei led to a >70% reduction in the enzyme activity. Further analysis to determine kinetic parameters suggests a mixed inhibition by apoferritin or apoferritin-nanoparticles, with a decrease in Vmax. Furthermore, the Km of the enzyme increased for both ATP and L-arginine substrates. Meantime, the inhibition constant (Ki) values for the apoferritin and apoferritin-nanoparticle interaction were in the submicromolar concentration ranging between 0.062 to 0.168 nm and 0.001 to 0.057 nM, respectively, for both substrates (i.e., L-arginine and ATP). Further kinetic analyses are warranted to aid the development of these nanoparticles as selective therapeutics. Also, more studies are required to elucidate the binding properties of these nanoparticles to arginine kinase of T. brucei.
Research Authors
Oluyomi Stephen Adeyemi 1,2,3,*, Afolake T. Arowolo 4, Helal F. Hetta 5,6 , Salim Al-Rejaie 7, Damilare Rotimi 3 and Gaber El-Saber Batiha 8
Research Journal
Molecules
Research Member
Research Pages
3432
Research Publisher
MDPI
Research Rank
1
Research Vol
25
Research Website
https://www.mdpi.com/1420-3049/25/15/3432/htm
Research Year
2020

Ameliorative Effects of Honey, Propolis, Pollen, and Royal Jelly Mixture against Chronic Toxicity of Sumithion Insecticide in White Albino Rats

Research Abstract
Sumithion (Fenitrothion) (SUM) is an organophosphorus insecticide used to combat a wide variety of plant pests. Exposure to SUM causes significant toxicity to the brain, liver, kidney, and reproductive organs through, for example, binding to DNA, and it induces DNA damage, which ends with oxidative stress. Therefore, the present study aimed to examine the protective role of bee products: a mixture of honey, propolis, palm pollen, and royal jelly (HPPJ) against SUM-induced toxicity. Twenty-four male albino rats (Rattus norvegicus) were classified into four groups, each containing six rats: control (corn oil), SUM (85 mg/kg; 1/20 LD50), HPPJ, and SUM + HPPJ once daily for 28 consecutive days. Blood samples were gently collected in sterilized ethylenediaminetetraacetic acid (EDTA) tubes for blood picture analyses and tubes without anticoagulant for serum isolation. Serum was used for assays of enzymatic and biochemical characteristics. The results revealed that SUM increased the weights of the liver, kidney, and brain as well as the enzymatic activity of glutathione peroxidase (GP), serum superoxide dismutase (SOD), and glutathione-S-transferase (GST). Additionally, SUM significantly increased the activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and γ-glutamyltransferase (γ-GT) and glucose, uric acid, and creatinine contents, while decreasing the acetylcholine esterase (AChE) activity and total lipids and total protein content. Furthermore, because of the inclusion of phenolic, flavonoids, terpenoids, and sugars, the HPPJ mixture counteracted the hematological, renal, and hepatic toxicity of SUM exposure.
Research Authors
Atef M.K. Nassar 1,* , Yehia M.M. Salim 1, Khalid S.A. Eid 1, Hazem M. Shaheen 2 , Abdullah A. Saati 3, Helal F. Hetta 4,5 , Amr Elmistekawy 6 and Gaber El-Saber Batiha 2,*
Research Journal
Molecules
Research Member
Research Pages
2633
Research Publisher
MDPI
Research Rank
1
Research Vol
25
Research Website
https://www.mdpi.com/1420-3049/25/11/2633
Research Year
2020

Assessing the Immunochromatographic Test Strip for Serological Detection of Bovine Babesiosis in Uganda

Research Abstract
In Uganda, bovine babesiosis continues to cause losses to the livestock industry because of shortages of cheap, quick, and reliable diagnostic tools to guide prescription measures. In this study, the presence of antibodies to Babesia bigemina and Babesia bovis in 401 bovine blood samples obtained from eastern and central areas of Uganda were detected using enzyme-linked immunosorbent assays (ELISAs) and immunochromatographic test strips (ICTs). The ELISA and ICT test used targeted the B. bigemina C-terminal rhoptry-associated protein (RAP-1/CT17) and B. bovis spherical body protein-4 (SPB-4). Using ELISA, single-ICT and dual-ICT, positive samples for B. bovis were detected in 25 (6.2%), 17 (4.3%), and 14 (3.7%) samples respectively, and positive samples for B. bigemina were detected in 34 (8.4%), 27 (6.7%), and 25 (6.2%), respectively. Additionally, a total of 13 animals (3.2%) had a mixed infection. The correlation between ELISA and single-ICT strips results revealed slight agreement with kappa values ranging from 0.088 to 0.191 between both methods, while the comparison between dual-ICT and single-ICT results showed very good agreement with kappa values >0.80. This study documented the seroprevalence of bovine babesiosis in central and eastern Uganda, and showed that ICT could, after further optimization, be a useful rapid diagnostic test for the diagnosis of bovine babesiosis in field settings.
Research Authors
Dickson Stuart Tayebwa 1,2,† , Amany Magdy Beshbishy 1,†, Gaber El-Saber Batiha 1,3,*,† , Mariam Komugisha 4, Byaruhanga Joseph 2, Patrick Vudriko 1,2, Ramadan Yahia 5,
Luay Alkazmi 6, Helal F. Hetta 7,8 , Naoaki Yokoyama 1 and Ikuo Igarashi 1,*
Research Journal
Microorganisms
Research Member
Research Pages
1110
Research Publisher
MDPI
Research Rank
1
Research Vol
8
Research Website
https://pubmed.ncbi.nlm.nih.gov/32722070/
Research Year
2020

Biogenesis, Biologic Function and Clinical Potential of Exosomes in Different Diseases

Research Abstract
Exosomes are extracellular vesicles (EVs) belonging to the nanovesicles family that function as signaling molecules between cells. After their first description in the late 1960s, interest in their potential as a research target has steadily increased. They are small secreted organelles with a single membrane that are well enriched in lipids, proteins, nucleic acids, and glycoconjugates. Exosomes take part in a larger communication network in which cells communicate between one another by DNA shuttling, proteins, RNA, and membrane-bound factors. The machinery of protein quality control occurs through the process termed “exosome biogenesis”. Furthermore, the pathway involved in intercellular movement of vesicles is vital in various aspects of human health and diseases. Due to their inherent properties, exosomes are currently being developed as potential therapeutic agents in a wide range of diseases including infectious and non-infectious diseases. Exosomes andother EVs sourced from Mesenchymal stem cells (MSCs) have been shown in different studies to possess therapeutic effects in diverse disease models either in vivo or in vitro. Some mechanisms and/or pathways that MSC-derived exosomes use to illustrate their therapeutic effect against some diseases have also been summarized. This review aims to highlight the recent findings and potential therapeutic application of exosomes in different diseases such as autoimmune, cardiovascular, obesity, neural, soft tissues, bone, and cartilage
Research Authors
Amany Magdy Beshbishy , Saad Alghamdi , ThankGod E. Onyiche, Muhammad Zahoor , Nallely Rivero-Perez 6 , Adrian Zaragoza-Bastida , Mohamed A. Ghorab , Ahmed Kh. Meshaal , Mohamed A. El-Esaw, Helal F. Hetta, and Gaber El-Saber Batiha
Research Journal
Applied Sciences
Research Member
Research Pages
4428
Research Publisher
MDPI
Research Rank
1
Research Vol
10
Research Website
https://dspace.nwu.ac.za/handle/10394/35301
Research Year
2020

Effects of Olive Leaf Extracts as Natural Preservative on Retailed Poultry Meat Quality

Research Abstract
Poultry meat is commonly marketed at refrigerated temperatures (2–5 ◦C). The major concern for retailers and consumers is the quality and safety of refrigerated poultry meat. During the chilling period, poultry meat undergoes too many undesirable changes due to microbial growth that leads to spoilage and economic loss. Therefore, this study was conducted to assess the effects of olive leaf extracts (OLE) used at three concentrations (0.25, 0.5, and 1%) on the sensory attributes, as well as the chemical and microbiological quality of raw poultry meat stored at 4 ± 1 ◦C for 15 days. The results revealed that the OLE addition reduced microbial growth successfully, and maintained the chemical quality and sensory attributes of poultry meat. Moreover, OLE extended the shelf-life of the poultry meat that held under proper refrigeration conditions up to 15 days compared to the control group, that was completely spoiled by the sixth day of storage. This study concludes that OLE could be used both as a natural antioxidant and an antimicrobial preservative for chilled poultry meat held at refrigerated temperature.
Research Authors
Ebeed Saleh, Alaa Eldin Morshdy, Eman El-Manakhly, Sarah Al-Rashed, Helal F. Hetta, Philippe Jeandet, Ramadan Yahia, Gaber El-Saber Batiha and Eman Ali
Research Journal
Foods
Research Member
Research Pages
1017
Research Publisher
MDPI
Research Rank
1
Research Vol
9
Research Website
https://www.mdpi.com/2304-8158/9/8/1017/htm
Research Year
2020

In Vitro Antibacterial Potential of Salix babylonica Extract against Bacteria that Affect Oncorhynchus mykiss and Oreochromis spp.

Research Abstract
Aquaculture development is limited by bacteria associated with several diseases; antibiotics are used for the treatment of these affections, but bacteria have developed resistance to these drugs. It is important to develop effective treatments that allow the production of antibiotic-free food. The aim of the present study is to evaluate the in vitro antibacterial effects of Salix babylonica hydro-alcoholic extract (SbHE) against Aeromonas hydrophila, Listonella anguillarum, Edwarsiella tarda, and Streptococcus iniae, bacteria that affect Oncorhynchus mykiss and Oreochromis spp. production. SbHE was obtained through the maceration technique. Reference strains were used and their sensitivity to antibiotics was determined. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of SbHE were determined. Results showed that three of four evaluated bacteria were multidrug resistant, except S. iniae. SbHE showed antibacterial activity against all bacteria. Results indicate an MIC of 1.56 to 25 mg/mL and an MBC of 3.12 to 100 mg/mL. The greatest inhibitory activity occurred against L. anguillarum obtaining a MIC of 1.56 mg/mL and an MBC of 3.12 mg/mL. Results indicate that SbHE has bactericidal activity against A. hydrophila, L. anguilalurm, and S. iniae as well as bacteriostatic activity against E. tarda and could be an alternative treatment against these bacteria.
Research Authors
Lenin Rangel-López , Adrian Zaragoza-Bastida , Benjamín Valladares-Carranza, Armando Peláez-Acero, Carolina G. Sosa-Gutiérrez , Helal F. Hetta, Gaber El-Saber Batiha , Ali Alqahtani and Nallely Rivero-Perez
Research Journal
Animals
Research Member
Research Pages
1340
Research Publisher
MDPI
Research Rank
1
Research Vol
10
Research Website
https://www.mdpi.com/2076-2615/10/8/1340/htm
Research Year
2020

Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood (Artemisia absinthium)

Research Abstract
Plants have been used since ancient times to cure certain infectious diseases, and some of them are now standard treatments for several diseases. Due to the side effects and resistance of pathogenic microorganisms to antibiotics and most drugs on the market, a great deal of attention has been paid to extracts and biologically active compounds isolated from plant species used in herbal medicine. Artemisia absinthium is an important perennial shrubby plant that has been widely used for the treatment of several ailments. Traditionally, A. absinthium has always been of pharmaceutical and botanical importance and used to manage several disorders including hepatocyte enlargement, hepatitis, gastritis, jaundice, wound healing, splenomegaly, dyspepsia, indigestion, flatulence, gastric pain, anemia, and anorexia. It has also been documented to possess antioxidant, antifungal, antimicrobial, anthelmintic, anti-ulcer, anticarcinogenic, hepatoprotective, neuroprotective, antidepressant, analgesic, immunomodulatory, and cytotoxic activity. Long-term use of A. absinthium essential oil may cause toxic and mental disorders in humans with clinical manifestations including convulsions, sleeplessness, and hallucinations. Combination chemotherapies of artemisia extract or its isolated active constituents with the currently available antibabesial or anti-malarial drugs are now documented to relieve malaria and piroplasmosis infections. The current review examines the phytoconstituents, toxic and biological activities of A. absinthium.
Research Authors
Gaber El-Saber Batiha , Ahmed Olatunde , Amany El-Mleeh , Helal F. Hetta , Salim Al-Rejaie , Saad Alghamdi , Muhammad Zahoor , Amany Magdy Beshbishy, Toshihiro Murata, Adrian Zaragoza-Bastida and Nallely Rivero-Perez
Research Journal
Antibiotics
Research Member
Research Pages
353
Research Publisher
MDPI
Research Rank
1
Research Vol
9
Research Website
https://pubmed.ncbi.nlm.nih.gov/32585887/
Research Year
2020

Antimicrobial resistance pattern and molecular genetic distribution of metallo-β-lactamases producing Pseudomonas aeruginosa isolated from hospitals in Minia, Egypt

Research Abstract
Background: Pseudomonas aeruginosa (P. aeruginosa) represents a great threat to public health worldwide, due to its high ability to acquire resistance to different antibiotic classes. Carbapenems are effective against multidrug resistant (MDR) P. aeruginosa, but their widespread use has resulted in the emergence of carbapenem-resistant strains, which is considered a major global concern. This study aimed to determine the prevalence of carbapenem resistance among P. aeruginosa strains isolated from different sites of infection. Methods: Between October 2016 and February 2018, a total of 530 clinical specimens were collected from patients suffering from different infections, then processed and cultured. Isolates were tested for extended spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) production using double-disk synergy test, modified Hodge tests, and disc potentia- tion test. PCR was used for the detection of selected OXA carbapenemases encoding genes. Results: Of 530 samples, 150 (28.3%) P. aeruginosa isolates were obtained. MDR strains were found in 66.6% (100 of 150) of isolates. Of 100 MDR P. aeruginosa isolates, 54 (54%) were ESBL producers and 21 (21%) carbapenem resistant P. aeruginosa. MBL production was found in 52.3% (eleven) carbapenem-resistant isolates. CTX-M15 was found among 55.5% of ESBL- producing P. aeruginosa. Carbapenemase genes detected were blaIMP (42.8%, nine of 21), blaVIM (52.3%, eleven of 21), blaGIM (52.3%, eleven of 21), blaSPM (38%, 8/21). In addition, isolates that were positive for the tested genes showed high resistance to other antimicrobials, such as colistin sulfate and tigecycline. Conclusion: Our study indicates that P. aeruginosa harboring ESBL and MBL with limited sensitivity to antibiotics are common among the isolated strains, which indicates the great problem facing the treatment of serious infectious diseases. As such, there is a need to study the resistance patterns of isolates and carry out screening for the presence of ESBL and MBL enzymes, in order to choose the proper antibiotic.
Research Authors
Sara M Farhan, Reham A Ibrahim, Khaled M Mahran Helal F Hetta, Rehab M Abd El-Baky
Research Journal
Infection and Drug Resistance
Research Member
Research Pages
2125–2133
Research Publisher
Dovepress
Research Rank
1
Research Vol
12
Research Website
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642648/
Research Year
2019
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