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Mohammed YI Al-Hamadani,1 Abdullah M Alzahrani,2 Mokhtar I Yousef,3 Maher A Kamel,4 Wael M El-Sayed1 1Department of Zoology Faculty of Science, Ain Shams University, Cairo 11566, Egypt; 2Department of Biological Sciences, King Faisal University, Ahsaa, Saudi Arabia; 3Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt; 4Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, EgyptCorrespondence: Wael M El-Sayed Tel +202/2482-1633Fax +202/2684-2123Email wael_farag@sci.asu.edu.egBackground and Aim: With the wide applications of chitosan and gold nanoparticles in drug delivery and many consumer products, there is limited available information about their effects on drug-metabolizing enzymes (DMEs). Changes in DMEs could result in serious drug interactions. Therefore, this study aimed to investigate the effects of exposure to chitosan or gold nanoparticles on hepatic Phase I and II DMEs, liver function and integrity, oxidative damage and liver architecture in male rats.Methods: Animals were divided into three equal groups: a control group, a group treated with chitosan nanoparticles (200 mg/kg, 50± 5 nm) and a group treated with gold nanoparticles (4 mg/kg, 15± 5 nm). Rats were orally administered their respective doses daily for 10 days.Results: Both chitosan and gold nanoparticles decreased the body weights by more than 10%. Gold nanoparticles reduced the activities of antioxidants (superoxide dismutase and catalase), and reduced glutathione level and elevated the malondialdehyde level in the liver. Gold nanoparticles caused significant reductions in CYP1A1, CYP2E1, quinone oxidoreductase1, and glutathione S-transferase and elevated CYP2D6 and N-acetyl transferase2. Chitosan elevated CYP2E1 and CYP2D6 and reduced UDP-glucuronosyltransferase 1A1. Both nanoparticles disturbed the architecture of the liver, but the deleterious effects after gold nanoparticles treatment were more prominent.Conclusion: Taken together, gold nanoparticles severely perturbed the DMEs and would result in serious interactions with many drugs, herbs, and foods.Keywords: CYP450, chitosan, drug interactions, drug metabolizing enzymes, oxidative stress

Mohamed A Ismail,1,2 Reem K Arafa,3 Magdy M Youssef,1,2 Wael M El-Sayed1,4 1Departments of Chemistry and Biological Sciences, College of Science, King Faisal University, Hofuf, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Department of Zoology, Faculty of Science, University of Ain Shams, Abbassia, Cairo, Egypt Abstract: A series of 15 monocationic bithiophenes and isosteres were prepared and subjected to in vitro antiproliferative screening using the full National Cancer Institute (NCI)-60 cell line panel, representing nine types of cancer. Among the nine types of cancer involved in a five-dose screen, non-small cell lung and breast cancer cell lines were the most responsive to the antiproliferative effect of the tested compounds, especially cell lines A549/ATCC, NCI-H322M, and NCI-H460, whereas compounds 1a, 1c, 1d, and 7 exhibited potent activity, with GI50 values (drug concentration that causes 50% inhibition of cell growth) from less than 10 nM to 102 nM. In addition, compounds 1c and 1d gave GI50 values of 73 nM and 79 nM, respectively, against the MDA-MB-468 breast cancer cell line. Structure–activity relationship findings indicated that the mononitriles were far less active than their corresponding monoamidines and, within the amidines series, the bioisosteric replacement of a thiophene ring by a furan led to a reduction in antiproliferative activity. Also, molecular manipulations, involving substitution on the phenyl ring, or its replacement by a pyridyl, or alteration of the position of the amidine group, led to significant alteration in antiproliferative activity. On the other hand, DNA studies demonstrated that these monoamidine bichalcophenes have promising ability to cleave the genomic DNA. These monoamidines show a wide range of DNA affinities, as judged from their DNA cleavage effect, which are remarkably sensitive to all kinds of structural modifications. Finally, the novel bichalcophenes were tested for their antioxidant property by the ABTS (2,2'-azino- bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt) assay, as well as lipid and nitric oxide scavenging techniques, and were found to exhibit good-to-potent antioxidant abilities. Keywords: bithiophenes, anticancer, DNA cleavage, antioxidant, Suzuki coupling, Stille coupling

Warda A Hussin,1,2,*,† Mohamed A Ismail,1,3,* Abdullah M Alzahrani,1 Wael M El-Sayed,1,4 1King Faisal University, College of Science, Departments of Chemistry and Biological Sciences, Hofuf, Saudi Arabia; 2Al-Azhr University, Faculty of Science, Department of Botany and Microbiology, Cairo, Egypt; 3Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt; 4University of Ain Shams, Faculty of Science, Department of Zoology, Abbassia, Cairo, Egypt *These authors contributed equally to this work †Warda A Hussin passed away on May 21, 2014 Abstract: A series of bichalcophene fluorobenzamidines 5a–e was synthesized from the corresponding mononitriles 4a–e via a direct reaction with lithium bis(trimethylsilyl)amide LiN(TMS)2 followed by de-protection with ethanolic HCl (gas). Bichalcophene fluorobenzonitriles 4a–e were prepared adopting a Stille coupling reaction between the bromo compounds 3a–c and 2-(tri-n-butylstannyl)furan or analogues. As an approach to drug discovery, the structure–antimutagenicity relationship of novel fluoroarylbichalcophenes was examined using the Ames Salmonella/microsomal assay. At nontoxic concentrations (10 and 20 µM), all derivatives alone or in combination with sodium azide (NaN3; 2 µg/plate) or benzo[a]pyrene (B[a]P; 20 µM) in the presence of S9 mix were not mutagenic. The fluoroaryl derivatives significantly reduced the NaN3-induced and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions. The recorded antimutagenic activity of fluoroaryl derivatives varied depending on the kind of mutagen and the exposure regimen. Monocationic fluoroarylbichalcophenes were superior to the corresponding mononitriles in reducing B[a]P-induced mutagenicity. Nevertheless, mononitriles were more active against NaN3, especially at low concentrations and under pre-exposure treatments. The antimutagenic activity was congruent with a high antioxidant activity that could promote the DNA repair system. The fluorine substitution changed the antimutagenic signature of bichalcophenes. Some of these compounds could be selected for further anticancer studies. Keywords: fluoroaryl-2,2’-bichalcophenes, stille coupling, Salmonella typhimurium, sodium azide, benzo[a]pyrene, antimutagenicity

Warda A Hussin,1 Mohamed A Ismail,2,3 Wael M El-Sayed2,41Al-Azhr University, Faculty of Science, Department of Botany and Microbiology, Cairo; 2King Faisal University, Faculty of Science, Departments of Biological Sciences and Chemistry, Al-Hufof, Ahsaa, KSA; 3Mansoura University, Faculty of Science, Department of Chemistry, Mansoura; 4University of Ain Shams, Faculty of Science, Department of Zoology, Abbassia, Cairo, EgyptAbstract: Antibiotic resistance is a major health problem; therefore, new antibacterial agents will need to be continuously developed. A series of novel bichalcophenes has been tested and found to have antimicrobial activity against selected bacteria. Due to the promising antimicrobial effects of these 4-substituted phenyl bichalcophene derivatives, the study reported here was launched to examine the interaction between novel bichalcophenes and tetracycline. The minimum inhibitory concentration values for all bichalcophenes were between 8 and 64 µM. Many of the bichalcophenes had synergistic activity that increased the inhibitory effect of tetracycline against bacterial growth, as indicated by the fractional inhibitory concentration index. The post-antibiotic effects of the novel bichalcophenes were determined. Many bichalcophenes were able to elongate the period required for bacteria to recover and grow after a brief exposure to tetracycline. Escherichia coli did not develop resistance to many bichalcophenes over a period of 7 days. A structural activity relationship could be characterized, as monocationic derivatives were more active than the corresponding mononitriles. The presence of a pyridyl group and/or furan ring reduced the activity, while the presence of a phenyl or thiophene ring enhanced the antibacterial activity. Our results suggest that bichalcophenes could be useful to elevate the shelf life of many antibiotics.Keywords: synergic interaction, fractional inhibitory concentration, post-antibiotic effect, resistant variants

Wael M El-Sayed,1,2 Warda A Hussin31King Faisal University, Faculty of Science, Departments of Biological Sciences and Chemistry, Al-Hufof, Ahsa, Kingdom of Saudi Arabia; 2University of Ain Shams, Faculty of Science, Department of Zoology, Cairo, Egypt; 3Al-Azhr University, Faculty of Science, Department of Botany and Microbiology, Cairo, EgyptAbstract: Evaluation of the potential antimutagenic activities of new compounds by Ames assay has been of great interest for the development of novel therapeutics for many diseases including cancer. Ten novel bichalcophenes with in vitro and in vivo broad spectrum activities against various microbial strains were investigated throughout the present study for their cytotoxic, antioxidant, and antimutagenic potential in a Salmonella reverse mutation assay system against sodium azide (NaN3) and benzo[a]pyrene (B[a]P). At nontoxic concentrations, all bichalcophenes alone or in combination with NaN3 (1 µg/plate) or B[a]P (20 µM) with S9 mix were not mutagenic. The bichalcophenes significantly reduced NaN3- and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions in a concentration-independent manner. However, the antimutagenic activity of bichalcophenes against B[a]P varied depending on the exposure regimen, being more effective under pre-exposure conditions. The antimutagenic activity was correlated with a high antioxidant activity that could promote the DNA repair system. Bichalcophenes are least likely to interfere with the microsomal bioactivation of B[a]P. Monocationic bichalcophenes were superior to the corresponding mononitriles as antimutagenic agents against both mutagens investigated, possibly due to the higher nucleophilic centers they have which could bind and protect the bacterial DNA. Three monocationic compounds were shown to have a strong anticancer activity against the 58 cell line. Based on the results of the present investigation, monocationic compounds (1, 4, and 5B) will be selected for further time consuming and costly chemoprevention studies in animal models.Keywords: bichalcophenes, Salmonella typhimurium, sodium azide, benzo[a]pyrene, antimutagenicity

Wael M El-Sayed,1,2 Warda A Hussin,3 Mohamed A Ismail1,41Departments of Biological Sciences and Chemistry, King Faisal University, Al-Hofuf, Saudi Arabia; 2Department of Zoology, University of Ain Shams, Cairo, Egypt; 3Department of Botany and Microbiology, Al-Azhr University, Cairo, Egypt; 4Department of Chemistry, Mansoura University, Mansoura, EgyptAbstract: The therapeutic efficacy of two novel bifurans and vancomycin in an animal model of a methicillin-resistant Staphylococcus aureus (MRSA) infection was compared. Adult male CF-1 mice (25–35 g) were intraperitoneally injected with 200 µL/mouse containing 107 cell-forming units of MRSA. After 16 hours, animals were treated with 110 mg/kg of vancomycin, or 5 mg/kg of mononitrile bifuran (1A) or monocationic bifuran (1B) and killed after 8 hours. Treatment with bifurans did not cause any toxicity. Treatment of MRSA-infected animals with bifurans resulted in significant reductions in the viable bacterial count in blood, liver, kidney, and spleen. Colonies recovered from livers and kidneys of mice injected with 1A or 1B lost the initial resistance pattern and became susceptible to methicillin and ciprofloxacin. MRSA elevated the serum urea level and activities of alanine aminotransferase and γ-glutamyl transpeptidase. MRSA also elevated the hepatic level of malondialdehyde, and serum levels of tumor necrosis factor and interleukin-6. MRSA also reduced the glutathione content and activities of catalase and glutathione S-transferase in liver. Similar to vancomycin, bifurans ameliorated most of the previous effects. Compound 1B was superior to 1A, and sometimes both provided better antistaphylococcal agents than vancomycin against MRSA pathogenesis. The present findings along with our previous studies support further evaluation of the efficacy of these bifurans in clinical studies.Keywords: MRSA, bifuran derivatives, septicemia, glutathione system, antioxidants

This study aimed to evaluate the protective potential of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ), both individually and in combination, against MTX-induced cardiotoxicity in male rats. A total of 36 rats were randomly divided into six groups (six animals each): control (vehicle), MTX alone (20 mg/kg, single dose), EMIQ+MTX (EMIQ at 26 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), Tau + MTX (Tau at 500 mg/kg, p.o. for 16 days, with a single dose of MTX on the 13th day), (EMIQ+Tau)+MTX, and (EMIQ+Tau)½+MTX. MTX treatment resulted in elevated levels of cardiac creatine phosphokinase-myocardial band, troponin I, nitric oxide, malondialdehyde, and serum IL-6, while decreasing levels of cardiac myeloperoxidase, catalase, and superoxide dismutase. MTX also reduced expression of BMI-1 , induced DNA laddering and fragmentation, and increased cleaved caspase-3 protein expression in cardiac tissue. Both Tau and EMIQ showed equivalent effectiveness in protecting the heart against MTX-induced damage due to their antioxidant, anti-inflammatory, and antiapoptotic properties. Notably, combined treatment with half-doses of Tau and EMIQ offered superior protection compared to full doses of each agent alone. The full-dose combination showed similar efficacy to the half-dose combination, with a few exceptions. Overall, these results suggest a synergistic effect of Tau and EMIQ in mitigating MTX-induced cardiotoxicity, warranting further investigation into the underlying mechanisms.

Background: Alzheimer's disease (AD) is a progressive and irreversible neurological disorder that gradually deteriorates an individual's ability to carry out even the simplest tasks., Objective: This study was undertaken to investigate the potential therapeutic efficacy of a novel bithiophene in a rat model of aluminum-induced AD pathology., Methods: A total of 108 adult male albino rats weighing 160 ± 20 g, were randomly assigned to six groups: (1) a control group administered DMSO, (2) group receiving a high dose of bithiophene (1 mg/kg), (3) a model group received AlCl 3 (100 mg/kg), those rats were then treated by either (4) bithiophene low dose (0.5 mg/kg), (5) high dose (1 mg/kg), or (6) memantine (20 mg/kg)., Results: Low dose bithiophene treatment was a promising strategy for mitigating oxidative stress and improving synaptic plasticity. This was demonstrated by reductions in malondialdehyde level, and increased activities of superoxide dismutase and catalase, and elevated glutathione content. Likewise, low dose bithiophene enhanced synaptic plasticity through a reduction in excitatory glutamate and norepinephrine levels, while increasing dopamine. Moreover, bithiophene significantly downregulated the expression of GSAP , GSK3 - β , and p53 , which are implicated in AD progression. This treatment also decreased caspase 3 and amyloid-β (Aβ 1-42 ) accumulation in the hippocampus. Finally, behavioral assessments revealed that low dose bithiophene significantly enhanced learning abilities, as proved by Morris water maze., Conclusions: Low dose bithiophene mitigated AD through ameliorating oxidative stress, promoting synaptic plasticity, inhibiting the Aβ accumulation, and enhancing the cognitive functions in a rat model., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aquaculture industry suffers significant limitations such as low resistance to diseases and expensive feed. This study investigated the antibacterial and immunostimulatory activities of ZnO-Ulva lactuca nanocomposite (ZnO-Ul NC) in the Procambarus clarkii. Zinc oxide nanoparticles (ZnO NPs) and ZnO-Ul NC were synthetized and characterized by electron microscopies as well as Fourier transform infrared spectroscopy. ZnO NPs and ZnO-Ul NC inhibited the growth of the isolated species Citrobacter freundii and Enterobacter hormaechei. For immunostimulatory evaluation, six crayfish groups (control, U. lactuca, ZnO L, ZnO H, ZnO-Ul L, and ZnO-Ul H) were fed on commercial diet, Ulva lactuca powder, and low or high dose of ZnO NPs or ZnO-Ul NCs, respectively for 90 days. The highest levels of total hemocyte count, granular cells%, phenoloxidase (PO) activity in hemolymph, and NO, superoxide dismutase (SOD), and GSH in hepatopancreas were all reported in the ZnO-Ul groups. The expression of proPO, SOD, and lysozyme exhibited the highest upregulation in the ZnO-Ul H group. Taken together, dietary ZnO-Ul NC significantly improved the non-specific immunity and antioxidant milieu of the crayfish at the genomic and proteomic levels. ZnO-Ul NC is cost effective, easily synthesized, and a promising immunostimulant for Procambarus clarkii that could be used in the aquaculture., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) remains of unknown etiology and lacks a cure. This study aimed to evaluate the therapeutic potential of a novel bithiophene derivative at two doses against AlCl 3 -induced AD in a rat model. Adult male rats (Rattus norvegicus) were divided into six groups (n=6): Group one consisted of naïve animals, group two received bithiophene (1 mg/kg) every other day for 30 days, and groups 3-6 were subjected to AlCl 3 (100 mg/kg, equivalent to 20.23 mg Al 3+ ) for 45 consecutive days. Groups four and five received low (0.5 mg/kg) or high (1 mg/kg) doses of bithiophene, respectively. Group six received memantine (20 mg/kg) daily for 30 days. All treatments were administered orally. Aluminum exposure resulted in severe degeneration of both histological and ultrastructural aspects of cells. Administration of the low dose of bithiophene significantly restored the number of CA1 pyramidal cells and the thickness of the stratum granulosum of the dentate gyrus. However, the high dose of bithiophene increased viable CA1 pyramidal cell numbers significantly without restoring the thickness of the stratum granulosum or reducing vacuolization or pyknotic changes. The low dose of bithiophene restored the normal histological and cytological structure of both cortical and hippocampal neurons affected by dementia. Further investigation is required to explore the molecular mechanisms underlying the ameliorative effects on Alzheimer's disease-induced deteriorations in the cortex and hippocampus., Competing Interests: Conflict of Interest The authors report no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cardiotoxicity is one of the most devastating complications of cancer treatment by methotrexate (MTX). The present study aimed to investigate the potential anti-cardiotoxic efficacy of taurine (Tau) and enzymatically modified isoquercitrin (EMIQ) alone or combined against MTX-induced cardiotoxicity in adult male rats. A total of 36 rats were randomly divided into six groups (six animals each): control, MTX (a single i.p. dose of 20 mg/kg), EMIQ + MTX (26 mg/kg of EMIQ, p.o. for 16 days), Tau + MTX (500 mg/kg of Tau, p.o. for 16 days), EMIQ + Tau + MTX at the same previous doses, and (EMIQ + Tau) ½  + MTX. MTX reduced the percentage of body weight change, the expression of dihydrofolate reductase (DHFR) and folypolyglutamyl synthetase (FPGS), the cleaved tumor necrosis factor alpha (TNF-α) level in the cardiac tissue, and the elevated serum TNF-α level. MTX extensively deteriorated the electrocardiography (ECG), inducing tachycardia with shortening of the time intervals between successive heartbeats (R-R interval), associated with elongation of ventricular depolarization (QRS interval), and the corrected total time for ventricular de- and repolarization (QTc) duration. Treatment with MTX resulted in a significant reduction in atrial depolarization (P amplitude) and rapid repolarization (T amplitude) and a significant elevation in plateau phase (ST height). MTX treatment resulted in swelling of cardiomyocytes with extensive vacuolization of sarcoplasm with numerous variably sized vacuoles in addition to apoptotic cells. Tau and EMIQ protected against MTX-induced deteriorations in the conductivity and rhythmicity of the heart through antioxidative, anti-inflammatory, and antiapoptotic activities. Treatment with tau and EMIQ combined at high or low doses offered superior protection to the heart than using each agent alone., (© 2024 John Wiley & Sons Ltd.)

Zinc oxide nanoparticles (ZnO NPs) have wide applications in daily life. Therefore, there is growing interest in the potential harmful impacts of these particles on human health. The present study was conducted to investigate the potential toxic effects of ZnO NPs (40 and 70 nm) compared to ZnO on the testes of rats. ZnO NPs were synthesized and characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). Adult male rats were randomly divided into four groups (n = 8): Group I (control), Group II (ZnO) received daily oral administration of ZnO (50 mg/kg), and Groups III and IV received daily oral administration of ZnO NPs of 40 nm or 70 nm at 50 mg/kg, respectively. All treatments continued for 50 consecutive days. ZnO and ZnO NPs reduced body and testis weights, sperm count and motility, serum luteinizing hormone (LH) and testosterone levels, testicular cytochrome p450 17A1 (CYP17A1) and cytochrome p450 1B1 (CYP1B1) concentrations, and the expression of p53 and cdk1. These treatments elevated testicular myeloperoxidase and serum acid phosphatase activities as well as sperm abnormalities. ZnO NPs reduced LH levels, which decreased CYP17A1 and CYP1B1, resulting in reduced synthesis of testosterone. ZnO NPs enhanced testicular inflammation and reduced cell viability. All these effects were manifested as reduced sperm motility and increased sperm deformities. Compared to macromolecules, nanoparticles exhibited significantly higher toxicity. The larger diameter ZnO NPs had more profound toxicity than the smaller-sized particles., (© 2024. The Author(s).)

The widespread use and applications of copper oxide nanoparticles (CuO NPs) in daily life make human exposure to these particles inevitable. This study was carried out to investigate the deteriorations in hepatic and serum biochemical parameters induced by CuO NPs in adult male mice and the potential ameliorative effect of L-arginine and quercetin, either alone or in combination. Seventy adult male mice were equally allocated into seven groups: untreated group, L-arginine, quercetin, CuO NPs, arginine + CuO NPs, quercetin + CuO NPs, and quercetin + arginine + CuO NPs. Treating mice with CuO NPs resulted in bioaccumulation of copper in the liver and consequent liver injury as typified by elevation of serum ALT activity, reduction in the synthetic ability of the liver indicated by a decrease in the hepatic arginase activity, and serum total protein content. This copper accumulation increased oxidative stress, lipid peroxidation, inflammation, and apoptosis as manifested by elevation in malondialdehyde, nitric oxide, tumor necrosis factor-α, the expression level of caspase-3 and bax quantified by qPCR, and the activity of caspase-3, in addition to the reduction of superoxide dismutase activity. It also resulted in severe DNA fragmentation as assessed by Comet assay and significant pathological changes in the liver architecture. The study proved the efficiency of quercetin and L-arginine in mitigating CuO NPs-induced sub-chronic liver toxicity due to their antioxidant, anti-inflammatory, and anti-apoptotic properties; ability to inhibit DNA damage; and the potential as good metal chelators. The results of histopathological analysis confirmed the biochemical and molecular studies., (© 2023. The Author(s).)

Background: Surgical treatment of benign thyroid disease varies from lobectomy, subtotal thyroidectomy, and total thyroidectomy (TT)., Objective: The current study aimed to compare complications of both total and subtotal thyroidectomy (STT) for patients with bilateral benign thyroid disorders., Methods: Sixty patients with benign goiter, 32 for TT and 28 for STT, where indications for surgery, operating time, hospital stay, and complications were studied., Results: The incidence of transient recurrent laryngeal nerve (RLN) palsy was (6.25%) for TT vs (3.57%) for STT, and temporary hypoparathyroidism was (9.38%) in TT patients compared to (7.14%) in STT patients. Permanent RLN palsy and hypoparathyroidism occurred only in one case (3.12%) from the TT group. No permanent complications occurred in STT patients. Recurrence of goiter occurred in two patients (7.14%) undergoing STT. Incidental papillary carcinoma was (7.14%) in STT patients and (3.13%) for follicular carcinoma in TT patients. There was no postoperative mortality., Conclusion: TT is a suitable surgical procedure in patients with bilateral benign thyroid disease as complication rate, operative time, and hospital stay are less comparable to STT. It will give a permanent cure without recurrences, and incidental thyroid malignancies can be avoided., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: One of the hypotheses that leads to an increased incidence of Alzheimer's disease (AD) is the accumulation of aluminum in the brain's frontal cortex. The present study aimed to evaluate the therapeutic role of a novel bithiophene derivative at two doses against AlCl 3 -induced AD in a rat model., Methodology: Adult male rats were divided into six groups, 18 rats each. Group 1: naïve animals, group 2: animals received a daily oral administration of bithiophene dissolved in DMSO (1 mg/kg) for 30 days every other day, groups 3-6: animals received a daily oral administration of AlCl 3 (100 mg/kg/day) for 45 consecutive days. Groups 4 and 5 received an oral administration of low or high dose of the bithiophene (0.5 or 1 mg/kg, respectively). Group 6; Animals were treated with a daily oral dose of memantine (20 mg/kg) for 30 consecutive days., Main Findings: Al disturbed the antioxidant milieu, elevated the lipid peroxidation, and depleted the antioxidants. It also disturbed the synaptic neurotransmission by elevating the activities of acetylcholine esterase and monoamine oxidase resulting in the depletion of dopamine and serotonin and accumulation of glutamate and norepinephrine. Al also deteriorated the expression of genes involved in apoptosis and the production of amyloid-β plaques as well as phosphorylation of tau. The new bithiophene at the low dose reversed most of the previous deleterious effects of aluminum in the cerebral cortex and was in many instances superior to the reference drug; memantine., Conclusion: Taking together, the bithiophene modulated the AD etiology through antioxidant activity, prevention of neuronal and synaptic loss, and probably mitigating the formation of amyloid-β plaques and phosphorylation of tau., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The current study aimed to test the antiproliferative activity of three azafuramidines (X, Y, and Z) against three different human cell lines; liver HepG2, breast MCF-7, and bone U2OS. And to explore the molecular mechanism(s) of the antiproliferative activity of these derivatives. The three new azafuramidines demonstrated a potent cytotoxicity at < 2 μM against the three cell lines investigated. The azafuramidines were highly selective with selectivity index ∼ 47 - 61 folds indicating safety to the normal cells. In the scratch assay, azafuramidines significantly reduced the percentage of wound healing indicating ability to prevent or reduce metastasis. Derivatives X and Z arrested the HepG2 cells at S and G2/M phases detected by the flow cytometry. Derivatives X, Y, and Z elevated the apoptosis of HepG2 cells by ∼ 71 %, 66 %, and 59 %, respectively. Derivatives X and Z were superior to derivative Y. The potent antiproliferative, cell cycle arrest, and pro-apoptotic efficacy of these chlorophenyl derivatives could be attributed to their ability of inducing the overexpression of p53, p21, and p27. These derivatives had the potential to act as anticancer agents and merit further investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1 H )-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, C 15 H 24 O 2 , have been probed by a Cremer-Pople puckering analysis. C-H···O hydrogen bonds generate chains in the crystal that stretch along the c -axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

A series of novel 1,3,4-thiadiazoles was synthesized via the reaction of N -(5-(2-cyanoacetamido)-1,3,4-thiadiazol-2-yl)benzamide (3) with different carbon electrophiles and evaluated as potential anticancer agents. The chemical structures of these derivatives were fully elucidated using various spectral and elemental analyses. Out of 24 new thiadiazoles, derivatives 4, 6b, 7a, 7d, and 19 have significant antiproliferative activity. However, derivatives 4, 7a, and 7d were toxic to the normal fibroblasts, and therefore were excluded from further investigations. Derivatives 6b and 19 with IC 50 at less than 10 μM and with high selectivity were selected for further studies in breast cells (MCF-7). Derivative 19 arrested the breast cells at G2/M probably through inhibition of CDK1, while 6b significantly increased the sub-G1 percent of cells probably through induction of necrosis. These results were confirmed by the annexin V-PI assay where 6b did not induce apoptosis and increased the necrotic cells to 12.5%, and compound 19 significantly increased the early apoptosis to 15% and increased the necrotic cells to 15%. Molecular docking showed that compound 19 was like FB8, an inhibitor of CDK1, in binding the CDK1 pocket. Therefore, compound 19 could be a potential CDK1 inhibitor. Derivatives 6b and 19 did not violate Lipinski's rule of five. In silico studies showed that these derivatives have a low blood-brain barrier penetration capability and high intestinal absorption. Taken together, derivatives 6b and 19 could serve as potential anticancer agents and merit further investigations., Competing Interests: Authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Anti-microbial resistance is an escalating worldwide threat. Thus, there is an utmost necessity for the introduction of novel anti-microbial agents. This research aimed to evaluate the in-vitro activity of plazomicin, meropenem-vaborbactam, and omadacycline against carbapenem-resistant Gram-negative isolates gathered from one Egyptian University group of Hospitals. 210 intensive care units (ICU) and 113 non-ICU samples were included. Resistance to carbapenems was reported in 37.5% and 21.05% of the isolated Gram-negative ICU and non-ICU organisms respectively (P < 0.001). Via disc diffusion, the sensitivity rates for carbapenem-resistant non-ICU and ICU strains were 68.8% & 64.4% for plazomicin, 68.8% & 48.9% for meropenem-vaborbactam, and 56.25% & 44.5% for omadacycline, respectively. Regarding MIC 50 / 90, it was 1/16 μg/mL for plazomicin and 4/32 μg/mL for both meropenem-vaborbactam and omadacycline separately. In conclusion, plazomicin displayed potent activity against carbapenem-resistant strains. Moreover, meropenem-vaborbactam and omadacycline demonstrated satisfactory results.

Introduction: Hepatocellular carcinoma (HCC) has different etiologies that contribute to its heterogeneity. In regards to the number of HCC patients, Egypt ranks third in Africa and fifteenth worldwide. Despite significant advancements in HCC diagnosis and treatment, the precise biology of the tumor is still not fully understood, which has a negative impact on patient outcomes., Methods: Advances in next-generation sequencing (NGS) have increased our knowledge of the molecular complexity of HCC., Results & Discussion: In this research, 16 HCC and 6 tumor adjacent tissues (control) of Child A Egyptian patients were successfully profiled for the expression profile of miRNAs by NGS. Forty-one differentially expressed miRNAs (DEMs) were found by differential expression analysis, with 31 being upregulated and 10 being downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then conducted on these differentially expressed miRNAs revealing that Sensitivity and specificity analysis showed that hsa-miR-4488, hsa-miR-3178, and hsa-miR-3182 were unique miRNAs as they are expressed in HCC tissues only. These miRNAs were all highly involved in AMPK signaling pathways. However, hsa-miR-214-3p was expressed in control tissues about eight times higher than in cancer tissues and was most abundant in "pathways in cancer and PI3K-Akt signaling pathway" KEGG terms. As promising HCC diagnostic markers, we here suggest hsa-miR-4488, hsa-miR-3178, hsa-miR-3182, and hsa-miR-214-3p. We further urge future research to confirm these markers' diagnostic and prognostic potential as well as their roles in the pathophysiology of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 EL-shqnqery, Mohamed, Samir, Ayoub, El-Sayed and Sayed.)

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide and the second cause of cancer-related deaths. It usually starts as an inflammation that progresses to adenocarcinoma. The goal of the present study was to investigate the antitumor efficacy of a new thiophene derivative against CRC in mice and explore the possible associated molecular pathways. The potential of this thiophene derivative to sensitize the CRC tumor tissue to a low dose of gamma irradiation was also investigated., Methods: Adult male mice were divided into seven groups; control, group treated with dimethylhydrazine (DMH) for the induction of CRC. The DMH-group was further divided into six groups and treated with either cisplatin, thiophene derivative, γ-irradiation, cisplatin + γ-irradiation, thiophene derivative + γ-irradiation, or left untreated., Results: DMH induced CRC as evidenced by the macroscopic examination of colon tissues and histopathology, and elevated the activities of cyclooxygenase2 (COX2) and nitric oxide synthase (iNOS). DMH also elevated kirsten rat sarcoma (KRAS) and downregulated the peroxisome proliferator activated receptor (PPARγ) as shown by RT-PCR and Western blotting. DMH exerted anti-apoptotic activity by reducing the expression of phosphorylated p53 and cleaved caspase3 at the gene and protein levels. The flow cytometry analysis showed that DMH elevated the necrosis and reduced the apoptosis compared to the other groups. The colon tissue from DMH-treated mice showed hyperplasia, aberrant crypt foci, loss of cell polarity, typical CRC of grade 4 with lymphocytes and macrophages infiltrating mucosa, muscularis mucosa, and submucosa score 3. Treatment with thiophene derivative or γ-irradiation ameliorated most of these deleterious effects of DMH. The concomitant action of thiophene derivative + γ-irradiation was typified by the better amelioration of tumor incidence and multiplicity, iNOS, PPARγ, p53, caspase 3, and histopathology of colon., Conclusion: Taken together, the new thiophene derivative is a promising therapeutic candidate for treatment of colorectal cancer in mice. It also sensitizes the CRC tumor to the ionizing radiation through anti-inflammatory and pro-apoptotic pathways., (© 2022. The Author(s).)

Background: Breast cancer is one of the leading causes of cancer-related morbidities. The present study aimed to evaluate the efficacy of bithiophene-fluorobenzamidine (BFB) against breast cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Swiss mice and reveal the underlining mechanisms., Methods: The mice were randomly divided into five groups; control, BFB-treated group, DMBA-treated group, and the last two groups received DMBA then tamoxifen or BFB., Results: BFB reduced the tumor incidence by ~ 88% versus 30% after TAM. DMBA significantly increased the expression of CDK1 and HER2 and reduced the expression of p53, p21 (CDKN1A), ESR-α, and CAS3. BFB caused significant down-regulation of CDK1 and HER2 and upregulation of p53, p21, ESR-α, and CAS3. In the DMBA-treated mice, cancerous cells metastasized to several organs. This was prevented by the administration of BFB. The antimetastatic and proapoptotic activities were confirmed in MCF7 cells in vitro by the wound healing and annexin V assays, respectively. Kaplan-Meier analysis showed that the BFB increased survival. In the DMBA group, tumors showed invasive carcinoma of grade III with central necrosis, polymorphism, mitotic activity, and numerous newly formed ductules, and colloidal mucinous secretions within adenoid cysts. BFB administration restored the normal structure of the mammary glands., Conclusion: Taken together, BFB has antitumor, pro-apoptotic, and anti-metastatic activities against breast cancer in mice and therefore, it merits further investigations., (© 2022. The Author(s).)

Fourteen new thienylnicotinamidines and their analogs 5a-5k, 12, 13a, and 13b were prepared and their antiproliferative potential was evaluated against the growth of 60 cancer cell lines. The tested compounds had a strong antiproliferative efficacy against almost all cancer cell lines, with the average GI 50 at ~2.20 µM. The effect of the thienylnicotinamidines on the growth of normal lung fibroblast cells (WI-38) indicated that these derivatives are safe to the normal cells. The selectivity index (SI) ranges from 5.5- to 42.0-fold. The conceivable mechanisms of action of the effective compounds 5d, 5f, 5g, 5i, 5j, and 5k with high SI were investigated. Although the thienylnicotinamidines are similar in structure, they could be divided into three groups as per their effects on gene expression: The first group (5d and 5f) elevated p53 and caspase 3 expression, the second group (5g and 5i) elevated p53 expression, and the last group (5j and 5k) elevated p53 and reduced topoII expression. Many thienylnicotinamides inhibited the vascular endothelial growth factor receptor-2 (VEGFR-2) in cell lysates at concentrations comparable to or better than pazopanib. The data of caspase 3 expression were confirmed by measuring the protein level by Western blot and the activity of the cleaved active enzyme. The ability to arrest the cell cycle and induce apoptosis was confirmed by flow cytometry. Taken together, two derivatives, 5d and 5f, with a distinctive VEGFR-2 inhibitory activity and a proapoptotic and cell cycle arrest profile merit further investigations., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Molecular hybrid of 2-indolinone-thiazolidinone is a well known scaffold for variable biological activities including anticancer activity. Accordingly, in the current work aided with structure-based molecular modeling studies, a library of novel twenty-six hybrids, 4(a-z), was designed and synthesized. Docking studies in the active site of CDK2, one of the key checkpoints enzymes, revealed that the binding scores of the designed molecules are comparable to the reference enzyme's inhibitors Sunitinib, Nintedanib, and Semaxanib. Variable antiproliferative activities are shown for these molecules against human liver (HepG2), breast (MCF7), and colon (HCT-29) cell lines considering Doxrubacin as a refrence drug. Compared to cytotoxic activities on the normal fibroblasts (WI-38), the tested molecules had better selectivity against the cancerous cells, expressed by their selectivity index (SI), than Doxrubacin and compound 4i was the safest compound. CDK2 inhibitory results of compounds 4f, 4g, 4h, and 4w showed IC 50 at 59.43, 143.6, 27.42, and 61.63 nM respectively, while that of Sunitinib was 23.8 nM. To clarify the obtained biological activities of these molecules, broad docking and molecular dynamic simulations studies were undertaken and confirmed the consistency between the computational and the in vitro CDK2 inhibitory activities. Furthermore, in silico ADME/Tox profiles were done for the most active molecules using SwissADME and pkCSM-pharmacokinetics web-based methods predicted good pharmacokinetics, bioavailability, and toxicity profiles for the tested compounds., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hyperthyroidism is associated with impairment in the neurotransmission and severe tissue damage in the brain. The present study explored the potential deleterious effects of experimentally-induced hyperthyroidism on the neurotransmitters, oxidative homeostasis, apoptosis and DNA fragmentation in cerebral cortex, thalamus & hypothalamus, and hippocampus in rats. Methods and Results: The ameliorative effects of N-acetylcysteine (NAC; 50 mg/kg, oral) and safranal (50 mg/kg, intraperitoneal) against hyperthyroidism (L-T4 500 µg/kg, subcutaneous) were investigated. All treatments continued daily over three weeks. Hyperthyroidism was manifested by significant elevations in serum fT3 and fT4 levels and a decline in serum TSH level and body weight. It was also characterized by significant elevations in the levels of dopamine, serotonin, and 5-hydroxyindole acetic acid, and monoamine oxidase activity to varying degrees in the brain regions examined and a significant reduction in norepinephrine in hippocampus only. Hyperthyroidism resulted in a significant oxidative stress in brain typified by elevations in malondialdehyde and nitric oxide content and reductions in glutathione level and SOD and catalase activities. This led to elevations in Caspases 9 and 3 and a reduction in Bcl2 resulting in DNA damage and confirmed by the histopathology of brain tissue. The administration of NAC or safranal with L-T4 prevented these deleterious effects by reducing the oxidative load and improving the brain antioxidant status. Conclusions: Hyperthyroidism disrupted the neurotransmitters in the brain which aggravated the oxidative stress and resulted in apoptosis. N-Acetylcysteine and safranal prevented these deleterious effects by enhancing the poor antioxidant milieu of the brain.

Background: Cancer exerts a huge strain on the health system. The emerging resistance to the current chemotherapies demands the continuous development of new anticancer agents with lower cost, higher efficacy, and greater specificity., Objective: This study aimed at developing selective small molecules as targeted anticancer agents., Methods: The behavior of benzoxazinone 2 towards nitrogen nucleophiles, such as hydrazine hydrate, formamide, ethanolamine, aromatic amines, and thiosemicarbazide, was described. The behavior of the amino quinazolinone 3 towards carbon electrophiles and P2S5 was also investigated. The antiproliferative activity of 17 new benzoxazinone derivatives was examined against the growth of three human cancer cell lines; liver HepG2, breast MCF-7, and colon HCT-29, in addition to the normal human fibroblasts WI-38, and the selectivity index was calculated. The possible molecular pathways, such as the cell cycle and apoptosis, were investigated., Results: Derivatives 3, 7, 8, 10, 13, and 15 had a significant (less than 10 μM) antiproliferative activity against the three cancer cell lines investigated. Derivative 7 showed the best antiproliferative profile comparable to that of doxorubicin. The selectivity index for all the effective derivatives ranged from ~5-12 folds, indicating high selectivity against the cancer cells. Derivative 15 caused ~ 7-fold and 8-fold inductions in the expression of p53 and caspase3, respectively. It also caused a ~ 60% reduction in the expression of both topoisomerase II (topoII) and cyclin-dependent kinase 1 (cdk1). Derivatives 3, 7, and 8 had a similar profile; ~ 6-8-fold increased in the expression of p53 and caspase3 but these compounds were devoid of any significant effect on the expression of topoII and cdk1. Derivatives 10 and 13 were also similar and resulted in a ~6-fold elevation in the expression ofcaspase3, and more than 60% downregulation in the expression of topoII. The results of the gene expression of topoII and caspase3 were confirmed by the measurement of the topoII concentration and caspase3 activity in the HepG2 cells., Conclusion: Six derivatives exerted their antiproliferative activity by arresting the cell cycle (decreasing cdk1), preventing the DNA duplication (downregulating topo II), and inducing apoptosis (inducing p53 and caspase3). One common feature in all the six active derivatives is the presence of a free amino group. These compounds have merit for further investigations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Acute myeloid leukemia (AML) is characterized by heterogeneity in phenotypic, genotypic, and clinical traits. miRNAs play an important role in pathogenesis and diagnosis of adult AML. Such information is not available about miRNA expression role in pediatric AML., Objective: We aimed to investigate the expression of miR-370 and miR-375 as new diagnostic biomarkers to discriminate pediatric AML patients and to predict their roles in the disease molecular basis., Methods: The expression of both miR-370 and miR-375 in peripheral blood (PB) of pediatric AML patients was assessed by QPCR; their impact for diagnosis was evaluated by ROC curve and their roles in pediatric AML development were predicted by bioinformatics analysis., Results: The expression of miR-370 and miR-375 levels was significantly decreased in pediatric AML patients, suggesting them as tumor suppressor miRNAs as supported by bioinformatics analysis. miR-370 showed better potential and sensitivity toscreen pediatric AML patients and more significant correlation with AML risk than miR-375. This is the first study to report the positive correlation between both miR-370 and miR-375., Conclusion: miR-370 level in peripheral blood can serve as a potential non-invasive diagnostic biomarker and was significantly correlated with AML risk. We strongly recommend PB miRNAs as diagnostic biomarkers for pediatric AML.

Background: Bowl or colorectal cancer (CRC) is the third most common type of cancer with about two million new cases every year. CRC is the second leading cause of cancer related mortalities., Objective: The study aims to evaluate the anticancer activity of ethanolic Ginger Extract (GE) in HCT-116 colon cells and colorectal tumors induced by dimethylhydrazine (DMH)., Methods: The antiproliferative activity was measured by MTT assay and the gene expression was assessed by q-RTPCR. For the antitumor study, rats were divided into five groups in random; control, group two was orally treated with 300 mg/kg of GE for 21 weeks, group three was s.c. injected with DMH (20 mg/kg) for 9 weeks, and groups four and five were treated with DMH and then treated with cisplatin (2.5 mg/kg, i.p) or GE, respectively, for 21 weeks., Results: GE had a significant antiproliferative activity with IC 50 ~ 12.5 µg/ml. GE induced both extrinsic and intrinsic apoptotic pathways. GE induced the expression of FasL, TRAIL, p53, and caspase-8 and downregulated Bcl-2 and survivin genes. Treatment of rats with DMH resulted in 100% tumor incidence and 2.3 tumors/rat. DMH significantly elevated the serum ALT, urea, and creatinine and significantly decreased the body weight gain. DMH also caused significant reductions in the hepatic GSH level, and the activities of catalase, SOD, GST, and GR in the liver as well as the renal GSH content and γ-GT activity. The colon from rats insulted with DMH showed adenomatous polyps with polymorphism and mitosis. The mucosa and submucosa were infested with inflammatory cells while serosa and muscularis were devoid from these cells. However, the muscularis was infiltrated with cystic formation, anaplastic changes, and hemorrhage. GE was able to alleviate all the previous deleterious effects of DMH and it was superior to cisplatin in its ameliorative effects. It did so without eliciting hepatotoxicity or nephrotoxicity which were shown in the group treated with DMH and cisplatin., Conclusion: This study proved that the antitumor activity of GE against the DMH induced-CRC is superior to cisplatin. GE was also safer than cisplatin and did not elicit hepatotoxicity or nephrotoxicity. GE induced apoptosis and has carcinostatic activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present study reports the synthesis and biological evaluation of a new series of novel N-(1,3,4-thiadiazol-2-yl)furan-2-carboxamide derivatives. The reactions were executed under both conventional and microwave irradiation conditions. An enhancement in the synthetic yields and rates was observed when the reactions were carried out under the microwave compared with the classical conditions. The structures of the products were ascertained by different analytical and spectral analyses. The antiproliferative activities were evaluated against three human epithelial cell lines; breast (MCF-7), colon (HCT-116), and prostate (PC-3) using MTT assay technique and doxorubicin was utilized as a reference drug. Besides, molecular docking studies were also performed and the vascular endothelial growth factor recptor-2 (VEGFR-2) was identified as a potential molecular target. Compounds 6, 7, 11a, 11b, 12, 14, and 16 showed promising antiproliferative activity against the three cancer cell lines investigated. Compounds 2 and 15b had significant antiproliferative activities against only colon and breast cells but not against the prostate cells. All the active antiproliferative compounds were highly selective. All the active antiproliferative compounds were good inhibitors of the VEGFR-2 at 7.4-11.5 nM compared with Pazopanib. Compound 7 with the most favorable orientation to the VEGFR-2 from the docking studies, was also the best inhibitor of the receptor. The antiproliferative activity of these compounds is in partial caused by their ability to inhibit the VEGFR-2 and since other molecular targets were not examined, other possibilities cannot be ruled out., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: This study was undertaken to investigate the efficacy of telomerase activator-65 (Ta-65) and pomegranate peel against aging-induced deteriorations in the liver., Materials and Methods: The rats were divided into four groups: control, aged, aged rats treated with Ta-65, and pomegranate orally for two months., Results: Aging significantly increased the serum levels of total protein, globulins, and protein carbonyl and reduced the insulin-like growth factor 1 (IGF-1). It also elevated the hepatic malondialdehyde and decreased the hepatic glutathione S-transferase (GST) activity. Aging elevated the expression of thioredoxin reductase1, telomerase reverse transcriptase, and cytochrome 3a1 in the liver; it increased the p53 protein level and elevated the activity of caspase-3 in the liver indicating the occurrence of apoptosis. The architecture of the liver deteriorated in the aged rats, as shown by both light and electron microscopy examinations. The liver of the aged rats had many apoptotic hepatocytes with shrunken nuclei. Many hepatocytes had dilated rough endoplasmic reticulum, many lysosomes, and many fat droplets. Administration of Ta-65 and pomegranate to the aged rats normalized most of the previous biochemical parameters and improved the liver architecture., Conclusion: Ta-65 and pomegranate have anti-aging activity through targeting multiple cellular pathways. It is also noteworthy that Ta-65 was superior to pomegranate in its alleviative effects., Competing Interests: The authors declare no conflicts of interest.

Background: Hepatocellular carcinoma (HCC) is the second most common cancer-related death in the world. No effective curative option exists for the treatment of HCC. The available drugs exhibit severe toxic effects and low therapeutic index., Aim: This work aimed to examine different monocationic arylthiophene derivatives for possible use as chemotherapeutic agents against HCC., Methods: The IC 50 values for the compounds were determined. The mechanism of cytotoxicity was further investigated using different methods., Results: Compound 2j proved to retain the highest cytotoxicity in comparison to as a positive control. The selectivity index of compound 2j revealed the safety to normal cells. Moreover, compound 2j was able to inhibit HepG2 cells´ migration and division. The anticancer effect of compound 2j was found to be partially via cell cycle arrest, activation of the tumour suppressor p53 protein, and induction of apoptosis via both intrinsic and extrinsic pathways. Compound 2j has a potential sensitization activity and significantly reduced the IC 50 values for the anticancer drugs doxorubicin, cisplatin, and taxol., Conclusion: The tested arylthiophenes showed a potent cytotoxicity against HepG2 cells and were safe to normal cells. The most active compound 2j was found to be able to inhibit cell division and migration and also to induce apoptosis. Compound 2j also proved to have a sensitization effect on standard anticancer drugs., (Copyright © 2021. Published by Elsevier Inc.)

In recent years, cell cycle and checkpoint pathways regulation are offering new therapeutic approaches against cancer. Isatin, is a well exploited scaffold in the anticancer domain. Accordingly, the current work describes the design and synthesis of two series of (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)hydrazinylidene)-thiazolidin-4-ones, 4(a-s) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene)hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-s). The structures of the synthesized molecules were confirmed by spectral and elemental methods of analyses. Pure diastereomers were further identified with 1 H- 1 H-NOESY and confirmed with X-ray crystallography. The target compounds were tested in vitro for their cytotoxicity against three human epithelial cell lines, liver (HepG2), breast (MCF-7), and colon (HT-29) in addition to the diploid human normal cells (WI-38) compared to doxorubicin as a reference drug. Variable cytotoxic effects (IC 50 3.29-100 µmol) were reported on the three cancer cell lines with pronounced selectivity compared to the normal one WI-38. The potency of the most active compounds, 4o, 4s, 5e, 5f, 5l, 5m and 5o (IC 50 3.29-9.92 µmol), in both series associated with the (Z) configurations of N = thiazolidin/ene or one, however, the configuration of the N = isatin moiety seemed to be of no importance to the activity. The tested compounds were grouped for their possible mechanism of action into 4 categories. Compound 4o with no apparent effect on all genes examined. Compounds 4s and 5o affected all genes investigated and seem to have multiple cellular targets; induced the expression of p53 and caspases, and downregulated that of CDK1. Compounds 5l and 5m directly elevated the expression of initiator and effector caspases without going through p53 pathway. Finally, compounds 5e and 5f elevated the expression of p53 and inhibited CDK1. Compounds 4s, 5e, 5f, 5l, 5m, and 5o caused a significant elevation in the activity of cleaved caspase 3 as well. Docking studies on CDK1 revealed that the active molecules bind to the tested enzyme by the same manner of the co-crystallized ligands and the isatin-thiazoldinone/ene scaffold is essential for binding of these molecules., (Published by Elsevier Inc.)

Background: Radiotherapy is the most common regimen for treating human cancers; however, ionizing radiation (IR) has hazardous effects on metabolically active organs such as the liver., Aim: This study aimed to investigate the possible protective (prophylactic and therapeutic) action of taurine against liver damage induced by gamma irradiation at different time intervals as well as the mechanisms by which taurine could provide its potential amelioration actions., Methods: In this study, 90 adult male rats (∼150 g) were randomly divided into five groups. Group 1 is the control group, group 2 received an oral daily dose (500 mg/kg) of taurine for two weeks, group 3 was exposed to a whole-body single dose of γ-irradiation (6 Gy), and groups 4 and 5 received taurine before or after γ-irradiation, respectively. Six rats from each group were sacrificed after 1, 2, and 3 weeks., Results: Over the period of the 3 weeks studied, there were significant increases in MDA, NO, TNF-α, and cytochrome-c levels and ALT, caspases-9 and -3 activities and significant decreases in GSH, SOD, CAT, and GPx in the irradiated group when compared with the relevant control. The liver of irradiated rats showed dilatation in the central and portal veins, edema, and degenerated hepatocytes., Conclusions: Taken together, IR caused maximum devastation in the liver 2 weeks after exposure as shown by elevation of the inflammatory and apoptotic markers and reducing the antioxidants. Taurine was able to alleviate the deleterious biochemical and histological effects whether given before or after IR. The magnitude of the observed protective effects was in both cases very similar.

Three thienylpicolinamidine derivatives 4a-c were prepared from their corresponding picolinonitriles 3a-c on treatment with lithium trimethylsilylamide, LiN(TMS) 2 , followed by a de-protection step using ethanol/HCl (gas). DFT calculations were used to optimize the geometric structure of the newly synthesized picolinamidines. The comparison of DFT calculated spectral data with the experimental data ( 1 H-NMR and 13 C-NMR) showed a good agreement. The in vitro antiproliferative activity of the cationic compounds 4a-c was determined against 60 cancer cell lines representing nine types of cancer. The tested picolinamidines were highly active with compounds 4a and 4b eliciting mainly cytotoxic activity with GI values ranging from -7.17 to -86.03. Leukemia (SR and K-562), colon (SW-620 and HT29), and non-small cell lung cancer (NCI-H460) cell lines were the most responsive to the investigated picolinamidines. In particular, 4-methoxyphenyl derivative 4a showed a profound growth deterring power with GI 50 of 0.34 μM against SR, 0.43 μM against SW-620, and 0.52 μM against NCI-H460. The three tested picolinamidines elicited potent GI 50 values against all tested cell lines at low micromolar to sub-micromolar level. The new picolinamidines were selective and did not affect normal human fibroblasts. The selectivity index ranged from 13-21 μM. The novel picolinamidines downregulated the expression of key genes in the cell cycle, cdk1 and topoII , but did not affect p53 or txnrd1 . Compounds 4b and 4c caused a significant reduction in the concentrations of TopoII and MAPK proteins but were devoid of any effect on the activity of caspase 3. Taken together, these promising anticancer candidates are effective at very low concentrations and safe to normal cells, and most probably work through arresting the cell cycle, and therefore, they deserve further investigations., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

By aging, male fertility and kidney function decline. Therefore, the investigation of health span-extending agents becomes more urgent to overcome aging-induced infertility and kidney dysfunction. The current research was undertaken to investigate the antiaging efficacy of Astragalus membranaceus telomerase activator-65 (Ta-65) and pomegranate supplements. Forty male Wistar rats were divided into young rats, aged rats, aged rats treated with Ta-65 (500mg/kg/day), and aged rats treated with pomegranate (250mg/kg/day). Testosterone, FSH, LH, and kidney functions were measured in serum. Sperm analysis as well as testicular histological examination was performed. Aging caused an imbalance in male sex hormones resulting in sperm abnormality and reductions in the sperm count and motility. Elevations in serum creatinine, uric acid, sodium, and potassium were reported in aged rats. Treatment with Ta-65 or pomegranate effectively ameliorated all the deteriorations induced by normal aging in male fertility and renal function. Ta-65 and pomegranate possessed strong antiaging activity by alleviating aging-induced male infertility through reestablishing the hormonal balance and testis architecture. They also alleviated the kidney dysfunction. On comparing Ta-65 with pomegranate, the improvement in FSH, LH, and sperm abnormalities caused by Ta-65 was much better than that caused by pomegranate., Competing Interests: CONFLICT OF INTEREST: The authors declared no potential conflicts of interest., (Copyright © 2020 The Author(s).)

Background and aim : The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2 H )-one derivatives. Methods : The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results : In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions : Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (This journal is © The Royal Society of Chemistry.)

Synthesis of 4-(3,5-dimethyl-1H-pyrazol-1-yl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine 1 and its functionalized reactions as nucleophile with various electrophilic reagents were performed through facile methods to yield different cyclic and acyclic derivatives (2-17). The structures of the newly synthesized compounds were established by their elemental analysis and spectral data. Derivatives 4, 14, 16, and 17 in addition to the parent compound 1 had IC 50 at ~4-10 µM against HepG2 and MCF7 and were selected for further investigations. All derivatives had high IC 50 values (>60 µM) against normal fibroblasts WI38 indicating selectivity against cancer cell lines. Derivatives 4, 14, and 17 up-regulated the expression of p53 by ~3-4 folds. All derivatives caused a significant ~3-fold increase in the expression of executive caspase 3 and significant elevation in cleaved caspase 3 activity. The elevation in the expression of caspase 3 by compound 1 and derivative 16 was not accompanied by an increase in p53 expression or cleaved caspase 3 activity. These two thienopyrimidines may act directly on caspase 3. Derivative 17 was unique in reducing the expression of Topo II by ~60%. The molecular docking showed that derivatives 4 and 17 with high binding energies could bind and inhibit Topoisomerase II (Topo II). In accordance with the docking modelling, derivatives 4 and 17 reduced the Topo II concentration by 82 and 90%, respectively, compared to the untreated cells. However, the parent compound 1 also caused a significant 34% reduction in the enzyme concentration although it was not predicted as a ligand for the enzyme in the docking study. Taken together, derivatives 4, 14 and 17 showed selective cytotoxicity, could arrest cell cycle, and induce apoptosis. Furthermore, they could serve as cytostatic agents by inhibiting/reducing Topo II., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer is among the leading causes of death worldwide. The incidence of deaths is expected to be 11.4 million in 2030., Objective: We aimed to evaluate the in vitro and in vivo antioxidant and antitumor activities of a novel Bithiophene- Fluorobenzamidine (BFB) against DMH-induced colorectal cancer in rats., Methods: The antiproliferative activity of BFB against HCT-116 colon cancer cells and apoptotic genes was assessed. In vivo study was also conducted in which 80 adult male rats were divided into 5 groups; control, BFB, and the other 3 groups were injected with DMH (20mg/kg, s.c., for 9 weeks). Group 4 was injected with 5 doses of cisplatin (2.5mg/kg, i.p over 21 weeks) and group 5 was injected with 3 doses/week of BFB (2.5mg/kg, i.p, for 21 weeks)., Results: BFB exhibited weak to moderate in vitro antioxidant activity. It had a strong antiproliferative activity with IC50 ~0.3µg/ml. BFB induced extrinsic apoptosis through the upregulation of FasL, TRAL, p53 and caspase-8, and intrinsic apoptosis through the downregulation of Bcl-2 and survivin. BFB decreased the tumor incidence, multiplicity and size and improved the decreased body weight. BFB also ameliorated the functions of kidney and liver and antioxidants deteriorated by DMH. BFB significantly improved the pathological changes caused by DMH in colon tissues., Conclusion: BFB showed a very promising antitumor activity against colorectal cancer induced by DMH in rats without causing hepato- or nephrotoxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Morbidity and mortality due to diabetes mellitus (DM) result in exorbitant psycho-economical costs, so there is a strong need to create new strategies and drugs for controlling DM. The aim of the current study was to investigate the anti-diabetic effect of the aqueous extract of Pterocarpus santalinus on streptozotocin (STZ)-induced DM as compared to glustin., Materials and Methods: Thirty male rats were divided into five groups of six rats each as follows: control; the second group, received the aqueous plant extract (250 mg/kg) orally and daily for three weeks; the third group, was intraperitoneally injected with a single dose of 65 mg/kg of STZ and sacrificed after four weeks; the fourth and fifth groups, were injected with STZ, then after one week these were treated orally with either plant extract or with 3 mg/kg of glustin for three weeks, then sacrificed., Results: HPLC analysis of the plant aqueous extract showed that it contains many polyphenols and flavonoids. Treatment with STZ resulted in significant reductions in body weight, insulin level, and the expression of Fetuin-A and IRS-1. It also caused significant elevations in glucose, HOMA-IR, glycated hemoglobin, urea, and the expression of JNK and SIRT-1. STZ also caused an extensive β-cell degranulation and decreased cellular density. The aqueous extract of red sandalwood was able to abrogate the deleterious effects caused by STZ and improved the histological architecture of pancreas., Conclusion: The aqueous extract of P. santalinus ameliorates diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function., Competing Interests: The authors declare no conflicts of interest.

A series of thirteen new aryl/hetarylbichalcophene-5-carboxamidines was prepared and screened for an in vitro anti-proliferative activity against sixty cancer cell lines. The tested monocationic bichalcophenes displayed promising potent anticancer activity against most cancer cell lines with GI 50 values of 1.34-3.09 μM. The most potent compound was derivative 8 (median GI 50 and TGI values of 1.34 and 3.23 μM, respectively), being also the least cytotoxic in this bichalcophene series with an LC 50 of 77.6 μM. The most responsive cancer cell lines were leukemia (SR and K-562) and colon (HCT-15 and HT29) with GI 50 in the sub-micromolar range. The effect of the tested bichalcophenes on normal human lung fibroblast (WI-38) cell line showed that they exerted their antiproliferative activity outside the realms of causing any toxicity in normal cells. To study apoptotic profiles of representatives of this class, compounds 4h, 4i, and 8 were found to cause significant reductions in cdk1 expression in HCT-116 colon cells by 46, 79, and 84%, respectively versus 52% reduction by 5- Flourouracil (5-FU). These three compounds were also unique being the only derivatives that significantly elevated the expression of p53 by ∼2, 4, and 5 folds, respectively. The tested bichalcophenes exhibited moderate to potent antioxidant activity in DPPH and ABTS as well as hydroxyl radical scavenging assays. Moreover, compounds IIIb, IIIc, 4c, and 4i, showed the highest pro-oxidant activity. Finally, to aid future endeavors for optimization of this series, a 5 descriptor 2D-QSAR model was derived from the common physicochemical parameters of these bichalcophenes and the external validation proved the model's good predictive efficiency., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Recombinant human interferon alpha2b (rhIFN-α2b) protein is FDA approved for treatment of many tumors and viral diseases. A rhIFN-α2b isoform has been produced and purified from the refolding reaction using high-resolution anion ion exchange chromatography. This isoform has a proper MW (19 kDa) and high purity and homogeneity. The conservation of native linear and conformational epitopes in this isoform was immunologically confirmed by Western blot and ELISA. Mass spectrometry assessment of its intact mass showed average mass (19,337 Da) equivalent to that of the expressed rhIFN-α2b protein without any chemical modification and without the first methionine. Peptide mapping of rhIFN-α2b through tryptic digestion of reductive/alkylated protein using urea as a denaturing agent gave the best pattern. The rhIFN-α2b had a high specific antiviral activity (2.5 × 10 8  ± 1.1 × 10 8 IU/mg protein). In vivo clearance study of rhIFN-α2b in female SD rats (500 μg/kg, intramuscularly) revealed rapid clearance (elimination half-life 0.54 h with a maximum plasma concentration of 33,792 pg/ml) compared with the commercial rhIFN-α2 (elimination half-life 0.75-0.96 h). In conclusion, the prepared rhIFN-α2b isoform has high purity, homogeneity, native like chemical and structural composition, high antiviral activity, and proper biological stability, which reduce its immunogenicity and raise its therapeutic efficiency.

Background: The genetic heterogeneity of tumor cells and the development of therapy-resistant cancer cells in addition to the high cost necessitate the continuous development of novel targeted therapies., Methods: In this regard, 14 novel benzoxazinone derivatives were synthesized and examined for anticancer activity against two human epithelial cancer cell lines; breast MCF-7 and liver HepG2 cells. 6,8-Dibromo-2- ethyl-4H-benzo[d][1,3]oxazin-4-one was subjected to react with nitrogen nucleophiles to afford quinazolinone derivatives and other related moieties (3-12). Benzoxazinone 2 responds to attack with oxygen nucleophile such as ethanol to give ethyl benzoate derivative 13. The reaction of benzoxazinone 2 with carbon electrophile such as benzaldehyde derivatives afforded benzoxazinone derivatives 14a and 14b.The structure of the prepared compounds was confirmed with spectroscopic tools including IR, 1H-NMR, and 13C-NMR., Results: Derivatives 3, 9, 12, 13, and 14b exhibited high antiproliferative activity and were selective against cancer cells showing no toxicity in normal fibroblasts. Derivative 3 with NH-CO group in quinazolinone ring was effective only against breast cells, while derivative 12 with NH-CO group in imidazole moiety was only effective against liver cells probably through arresting cell cycle and enabling repair mechanisms. The other derivatives (9, 13, and 14b) had broader antiproliferative activity against both cell lines. These derivatives enhance the expression of the p53 and caspases 9 and 3 to varying degrees in both cell lines. Derivative 14b caused the highest induction in the investigated genes and was the only derivative to inhibit the EGFR activity., Conclusions: The unique features about derivative 14b could be attributed to its high lipophilicity, high carbon content, or its extended conjugation through planar aromatic system. More investigations are required to identify the lead compound(s) in animal models., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In a continuous combat against cancer, which is one of the leading causes of mortality now, chalcone and Schiff bases moieties have been incorporated and their antiproliferative activities and associated mechanisms against liver (HepG2) and breast (MCF-7) cell lines in addition to normal fibroblasts (WI-38) have been examined., Methods: Derivatives 4 and 5 of Schiff bases only and chalcone derivatives of Schiff bases 1 and 2 were devoid of any antiproliferative activity. All three compounds (3, 6, and 7) with significant antiproliferative activity were selective and caused no growth inhibition in normal fibroblasts. Derivative 3 was a chalcone only with IC50 of ~20 µM and has a very interesting signature where it enhanced apoptosis in HepG2 by stimulating the expression of downstream execution caspase 3 without affecting neither p53 nor initiator caspase 9. In spite of the structural similarity between compounds 6 and 7, compound 6 discerned itself with a unique IC50 of ~ 10 µM., Results: The antiproliferative activity of derivative 6 could be attributed to its unique capability of formation of free radicals such as phenoxide radicals which arrested the cell cycle through enhancing the expression of p53 and induced apoptosis by induction of both caspases 9 and 3. It was the only investigated derivative that inhibited the tyrosine kinase activity by 89%., Conclusions: The antiproliferative activity of the compounds under investigation considerably depended on the nature of the substituent at position 4 in phenyl rings of both chalcone and Schiff base fragments. Derivative 6 with electron withdrawing chlorine substitution on the phenyl ring of Schiff base fragment and an electron donating methoxy group on the phenyl ring of chalcone fragment was the most active member., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chemotherapeutic drugs have high toxicity associated with undesirable side-effects. Now, natural products are the most important anti-cancer agents because of their low toxicity and potential effectiveness., Methods: The half maximal inhibitory concentration (IC50) of amygdalin, naringenin and ellagic acid against breast, colon, and liver cell lines was estimated. The antimutagenic, free radical-, superoxide radical-, and hydroxyl radical- scavenging activities of these phytochemicals were measured. The expression of p53, bid, bax, bcl2, and caspases 9, 3, and 7 was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in breast and liver cells. In addition, the active Caspase 3 protein was estimated in liver cells., Results: Ellagic acid showed the highest antioxidant and antiproliferative activities. Amygdalin and naringenin with low and moderate antioxidant profiles showed a corresponding low and moderate cytotoxicity against cancer cell lines, respectively. Naringenin and ellagic acid had a significant antimutagenic activity which was detected by the Salmonella test. Ellagic acid offered a much better antimutagenic activity than naringenin. The apoptotic pathway evoked by ellagic acid in HepG2 and MCF-7 cells was investigated. The results showed that a caspase-dependent and a caspase-independent apoptosis occurred in MCF-7 and HepG2, respectively., Conclusion: The antimutagenic/antioxidant properties are well correlated with the antiproliferative activity of the phytochemicals investigated. This study proved that some easy, quick and cheap assays could predict the antiproliferative activity of many nutraceuticals. Finally, this platform could help in the discovery of new anticancer agents where hundreds of compounds are investigated in the pipeline of drug discovery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents., Aims: This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved., Methods: The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin., Results: A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β-epoxy-1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression., Conclusion: Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Exposure to ionizing radiation (IR) is inevitable since over 80% of total average exposure comes from natural sources. Brain is vulnerable to the deleterious effects of IR. Therefore, scientists paid attention in identifying novel compounds to protect against radiation-induced brain injury. Adult male albino rats weighing 120-150 g were divided into five groups, 18 rats each. Group 1 served as control, group 2 received an oral daily dose of taurine (500 mg/kg) for 2 weeks. Group 3 was exposed to a whole body single dose of γ-irradiation (6 Gy). Groups 4 and 5 received taurine before and after γ-irradiation, respectively. Six rats from each group were sacrificed after 1, 2 or 3 weeks. Throughout the 3 weeks studied, there were significant increases in MDA, NO, TNF-α levels, and Cytochrome-c and activities of Caspases -9 and -3 and significant decreases in GSH, SOD, CAT and GPx in the irradiated group when compared with the relevant control. Cerebral cortex of irradiated rats showed vacuolization and nuclear pyknosis in the neuronal cells and focal gliosis. Taurine administration pre- or post-irradiation significantly ameliorated all these previous effects. Taurine had antioxidant, anti-inflammatory, and anti-apoptotic effects and ameliorated the histopathological changes in brain in a time-dependent mode., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The objective of this study is to investigate the toxic effects of aluminum and the potential alleviation of selenite and N-acetylcysteine (NAC) on this toxicity. Acute aluminum toxicity was induced by intraperitoneal (i.p.) injection of AlCl 3 (30 mg Al 3+ /kg) for four consecutive days. Al 3+ damaged the synthetic capability and regeneration power of liver cells and induced inflammation. It also damaged the kidney and disturbed the lipid profile enhancing the total cholesterol level and LDL-cholesterol level increasing the risks of atherosclerosis. Al 3+ reduced the cellular antioxidant milieu typified by the decrease in reduced glutathione, vitamin E, and four antioxidant enzymes and induced lipid peroxidation (LPO). Selenite at 1 mg Se/kg and NAC at 150 mg/kg injected either simultaneously with or after Al 3+ mitigated most of these damaging effects probably by the virtue of scavenging the free radicals, binding aluminum and stimulating its excretion and reducing its bioavailability, bolstering the endogenous antioxidant defense systems, stabilizing the cell membrane, and preventing LPO. The beneficial effects of selenite and NAC against aluminum toxicity were also confirmed by the light and electron histopathology study. There were no significant differences between the two regimens used (protection and therapeutic) in the current study probably due to the short time of exposure, and the abrogation of Al 3+ toxicity offered by selenite was better than that provided by NAC on the histopathology level.