Search

Mercuric chloride (HgCl2) is extremely toxic to both humans and animals. It could be absorbed via ingestion, inhalation, and skin contact. Exposure to HgCl2 can cause severe health effects, including damages to the gastrointestinal, respiratory, and central nervous systems. The purpose of this work was to explore if carvacrol (CRV) could protect rats lungs from damage caused by HgCl2. Intraperitoneal injections of HgCl2 at a dose of 1.23 mg/kg body weight were given either alone or in conjunction with oral CRV administration at doses of 25 and 50 mg/kg body weight for 7 days. The study included biochemical and histological techniques to examine the lung tissue's oxidative stress, apoptosis, inflammation, and autophagy processes. HgCl2‐induced reductions in GSH levels and antioxidant enzymes (SOD, CAT, and GPx) activity were enhanced by CRV co‐administration. Furthermore, MDA levels were lowered by CRV. The inflammatory mediators NF‐κB, IκB, NLRP3, TNF‐α, IL‐1β, IL6, COX‐2, and iNOS were all reduced by CRV. When exposed to HgCl2, the levels of apoptotic Bax, caspase‐3, Apaf1, p53, caspase‐6, and caspase‐9 increased, but the levels of antiapoptotic Bcl‐2 reduced after CRV treatment. CRV decreased levels of Beclin‐1, LC3A, and LC3B, which in turn decreased HgCl2‐induced autophagy damage. After HgCl2 treatment, higher pathological damage was observed in terms of alveolar septal thickening, congestion, edema, and inflammatory cell infiltration compared to the control group while CRV ameliorated these effects. Consequently, by preventing HgCl2‐induced increases in oxidative stress and the corresponding inflammation, autophagy, apoptosis, and disturbance of tissue integrity in lung tissues, CRV might be seen as a useful therapeutic alternative. [ABSTRACT FROM AUTHOR]

Introduction Campylobacter jejuni is an enteric pathogen that has emerged as one of the most common causes of bacterial gastroenteritis and a major public health concern in the developed world [...], The glycolytic pathway of the enteric pathogen Campylobacter jejuni is incomplete; the absence of phosphofructokinase means that the suppression of futile cycling at this point in the glycolytic--gluconeogenic pathway might not be required, and therefore the mechanism for controlling pathway flux is likely to be quite different or absent. In this study, the characteristics of fructose-1,6-bisphosphatase (FBPase) of C. jejuni are described and the regulation of this enzyme is compared with the equivalent enzymes from organisms capable of glycolysis. The enzyme is insensitive to AMP inhibition, unlike other type I FBPases. Campylobacter jejuni FBPase also shows limited sensitivity to other glycolytic and gluconeogenic intermediates. The allosteric cooperative control of the enzyme's activity found in type I FBPases appears to have been lost. Key words: Campylobacter jejuni, glycolysis, gluconeogenesis, metabolic control, fructose-1,6-bisphosphatase. La voie glycolytique de l'agent pathogene enterique Campylobacter jejuni est incomplete; l'absence de phosphofructokinase signifie que la suppression du cycle futile a cette etape de la voie glycolyse--gluconeogenese pourrait ne pas etre necessaire et qu'en consequence, le mecanisme de controle du flux de la voie est probablement tres different ou absent. Dans cette etude, les caracteristiques de la fructose-1,6-bisphosphatase (FBPase) de C. jejuni sont decrites et la regulation de cette enzyme est comparee a celle d'enzymes equivalentes d'organismes capables de realiser la glycolyse. L'enzyme est insensible a l'inhibition par l'AMP, contrairement aux autres FBPases de type I. La FBPase de C. jejuni montre aussi une sensibilite limitee envers d'autres intermediaires de la glycolyse et de la gluconeogenese. Le controle cooperatif allosterique de l'activite de l'enzyme trouve chez les FBPases de type I semble aussi avoir ete perdu. [Traduit par la Redaction] Mots-cles: Campylobacter jejuni, glycolyse, gluconeogenese, controle metabolique, fructose-1,6-bisphosphatase.

Diclofenac (Dic) was shown to increase in reactive oxygen species (ROS) levels thereby resulting oxidative stress and apoptotic cell death in colon cancer. The antioxidants can prevent and repair oxidative damage caused by ROS. The aim of this study was to assess the effect of chrysin (Chr) on Dic-induced toxicity in HT-29 and molecular mechanisms underlying its effect. Cell proliferation and cytotoxicity assays were carried out by WST-1 and LDH leakage assay, apoptotic index was calculated by TUNEL Assay, antioxidant parameters were studied by measurement of ROS, LPO and TAS levels and catalase activity, expression of caspase-3 protein levels were analyzed by immunohistochemical staining, mRNA levels of apoptotic and anti-apoptotic genes were studied by qRT-PCR. The cellular processes of Dic-triggered cell death was associated with increase in ROS, malondialdehyde levels and lactate dehydrogenase release, decrease in total antioxidant and catalase activity while pretreatment with Chr reversed these effects. The expression level of p53, cas-3, cas-8, Bax and cytochrome c increased in Dic-exposed group while they were reduced by Chr. The use of antioxidant nutritional supplements, and in particular of Chr, may reduce the efficacy of Dic in inducing apoptosis of colon cancer cells. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) plays a key function in various biochemical processes as they produce reducing power of the cell. Thus, metabolic reprogramming of nicotinamide adenine dinucleotide homeostasis is reported to be an important step in cancer progression as well as in combinational therapeutic approaches. In this study, the effects of the antibiotics, furosemide, cefazolin, cefuroxime, gentamicin and clindamycin on rat erythrocyte G6PD enzyme was studied in in vitro conditions. The enzyme was purified by 2', 5'-adenosine diphosphate Sepharose 4B affinity chromatography in a single purification step with 1825 fold and 83.7% yield. The specific activity of the enzyme was 29.2 EU/mg proteins. The inhibition studies of these antibiotics were carried out on the enzyme revealing that gentamicin, clindamycin and furosemide inhibited the activity of the G6PD with an IC50 of 1.75, 34.65 and 0.526 mM, respectively with Ki of 0.7, 39.8 and 0.860 mM, respectively. All inhibition types were analyzed by Lineweaver-Burk diagram showing noncompetitive inhibition for furosemide and gentamicin while clindamycin inhibited the activity competitively. On the other hand, cefazolin and cefuroxime increased the activity of the enzyme. [ABSTRACT FROM AUTHOR]

Abstract: Glucose‐6‐phosphate dehydrogenase (G6PD) and 6‐phosphogluconate dehydrogenase (6PGD) play an important function in various biochemical processes as they generate reducing power of the cell. Thus, metabolic reprogramming of reduced nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis is reported to be a vital step in cancer progression as well as in combinational therapeutic approaches. In this study, N‐benzoylindoles 9a‐‐9d, which form the main framework of many natural indole derivatives such as indomethacin and N‐benzoylindoylbarbituric acid, were synthesized through three easy and effective steps as an in vitro inhibitor effect of G6PD and 6PGD. The N‐benzoylindoles inhibited the enzymatic activity with IC50 in the range of 3.391505 μM for G6PD and 2.19–990 μM for 6PGD. [ABSTRACT FROM AUTHOR]

Natural and synthetic derivatives that contain an indole core are being used in medical treatments and technological processes. Therefore, the development of new synthetic methods for the synthesis of indole derivatives is very popular. In this study, new oxindoles with reaction of 4,7-dihydro-1H-indole (2) and isatin (4) were synthesized as analogs of natural product 3,3'-bis(indolyl)oxindole. The biological properties of the compounds obtained during this study were also studied, showing that compounds 5, 7, and 12 inhibited the activity of G6PD with an IC50 of 99 μM, 231 μM, and 304 μM respectively. The activity of rat erythrocyte 6PGD was increased in the presence of 5 and 7 and was inhibited in the presence of 12. As indole derivative 5 was an activator of 6PGD and inhibitor of G6PD, it was selected for docking studies to understand the mechanism of activation and inhibition. [ABSTRACT FROM AUTHOR]

Nepeta baytopii is a poorly studied, endemic Nepeta species (Lamiaceae) of Turkey. For the first time, the biological activities (antioxidant, enzyme inhibition, and cytotoxicity properties) of the hexane, ethyl acetate, methanol, water/methanol, and water extracts and essential oil prepared from N. baytopii aerial parts were assessed. Hydro-methanol (41.25 mg gallic acid equivalent (GAE)/g) and water extracts (50.30 mg GAE/g), respectively showed the highest radical scavenging (94.40 and 129.22 mg Trolox equivalent (TE)/g, for 2,2-diphenyl-1-picrylhydrazyl radical and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid radical scavenging assays) and reducing (229.37 and 129.55 mg TE/g, for ferric-reducing antioxidant power and cupric-reducing antioxidant capacity assays) capacities in vitro. An interestingly high inhibition was observed for ethyl acetate extract against butyrylcholinesterase (10.85 mg galantamine equivalent/g). The methanol extract showed high cytotoxicity (31.7%) against HepG2 cells. Caryophyllene oxide was identified in high concentrations in the essential oil (39.3%). Luteolin and apigenin and their derivatives were identified from the methanol and water extracts. The results obtained from this study highlighted that the abundance of highly bioactive compounds from Nepeta baytopii ensures the multiple biological activities of the tested extracts, and this suggests a potential use in the pharmaceutical and nutraceutical fields, and therefore should be investigated further. [ABSTRACT FROM AUTHOR]

Background: The glutathione S-transferases (GSTs) are family of enzymes that are notable for their role in phase II detoxification reactions. Antibiotics have been reported to have several adverse effects on the activity of the enzymes in mammals., Aim: The aim of this study was the structural and biochemical characterization of rat erythrocyte GST and understanding the effects of gentamicin, clindamycin, cefazolin, ampicillin and scopolamine butylbromide on the activity of human erythrocyte GST using rat as a model., Methods: The enzyme was purified by GSH-agarose affinity chromatography. In vitro GST enzyme activity was measured at 25°C using CDNB as a model substrate. IC50 of drugs was measured by activity % vs compound concentration graphs. Lineweaver Burk graphs were drawn to determine the inhibition type and Ki constants for the drugs. The structure of the enzyme was predicted via Protein Homology/analogy Recognition Engine., Results: In this study, GST was purified from rat erythrocyte with a specific activity of 6.3 EU/mg protein, 44 % yield and 115 fold. Gentamicin and clindamycin inhibited the enzymatic activity with IC50 of 1.69 and 6.9 mM and Ki of 1.70 and 2.36 mM, respectively. Ampicillin and scopolamine butylbromide were activators of the enzyme, while the activity of the enzyme was insensitive to cefazolin. The enzyme was further characterized by homology modeling and sequence alignment revealing similarities with human GST., Conclusion: Collectively, it could be concluded that gentamicin and clindamycin are the inhibitors of erythrocyte GST., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)