ABSTRACT
BACKGROUND: Thioredoxin reductase (E.C 1.6.4.5.; TrxR) is a widely distributed flavoprotein that catalyzes the NADPH-dependent reduction of thioredoxin (Trx) in many cellular events such as DNA synthesis, DNA repair, angiogenesis, antioxidative defense, and regulating apoptosis. Although TrxR is indispensible in protecting cells against oxidative stress, the overexpression of TrxR is seen in many aggressive tumors. Therefore, targeted inhibition of TrxR has been accepted as a new approach for chemotherapy. OBJECTIVE: In this study, in vitro inhibition effect of the lichen acids (diffractaic, evernic, lobaric, lecanoric, and vulpinic acid) on mitochondrial TrxR purified from rat lung was investigated. METHOD: It was the first time the enzyme was purified from rat lungs by using 2', 5'-ADP Sepharose 4B affinity chromatography. The purity of the enzyme was checked with SDS-PAGE. In vitro inhibition effect of the lichen acids was investigated spectrophotometrically. To emphasize the importance of the obtained data, the commercial anticancer drugs cisplatin and doxorubicin were used as positive controls. RESULTS: Molecular mass of the enzyme was calculated as approximately 52.4 kDa. The enzyme was purified with a 63.6% yield, 208.3 fold, and 0.5 EU/mg proteins specific activity. The IC50 values of five lichen acids were significantly lower than IC50 values of anticancer drugs. CONCLUSION: All of the lichen acids, especially lecanoric and vulpinic acid, exhibited much stronger inhibitory effect on TrxR than the anticancer drugs cisplatin and doxorubicin. These lichen acids have pharmacological potential as effective natural antioxidants, antimicrobials, and anticancer agents.
Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Lichens/chemistry , Lung/enzymology , Thioredoxin-Disulfide Reductase/antagonists & inhibitors , Animals , Anisoles/chemical synthesis , Anisoles/chemistry , Anisoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cisplatin/chemistry , Cisplatin/pharmacology , Depsides/chemical synthesis , Depsides/chemistry , Depsides/pharmacology , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Doxorubicin/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Furans/chemical synthesis , Furans/chemistry , Furans/pharmacology , Hydroxybenzoates/chemical synthesis , Hydroxybenzoates/chemistry , Hydroxybenzoates/pharmacology , Lactones/chemical synthesis , Lactones/chemistry , Lactones/pharmacology , Male , Mitochondria/drug effects , Mitochondria/metabolism , Molecular Structure , Phenylacetates/chemical synthesis , Phenylacetates/chemistry , Phenylacetates/pharmacology , Rats , Rats, Sprague-Dawley , Salicylates/chemical synthesis , Salicylates/chemistry , Salicylates/pharmacology , Structure-Activity Relationship , Thioredoxin-Disulfide Reductase/isolation & purification , Thioredoxin-Disulfide Reductase/metabolismABSTRACT
In this research, the genotoxic and antigenotoxic effects of methanol extract of Sempervivum armenum (MSA) were studied using micronucleus (MN) test and sister chromatid exchange (SCE) test systems in cultured human peripheral blood cells. According to the SCE and MN tests results, MSA reduced the genotoxic effects of aflatoxin B1. In order to explain the reason for the antigenotoxic effects of MSA, antioxidants levels were determined. Cotreatments of 5, 10, 20 mg/mL concentrations of MSA with aflatoxin B1 decreased the frequencies of SCE, MN and the malondialdehyde level and increased the amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin. The results of this experiment showed that MSA has strong antioxidative and antigenotoxic effects and this antigenotoxic activities of MSA can be due to the antioxidant activities.
ABSTRACT
In this article, the genotoxic and antigenotoxic effects of methanol extract of of Cladonia foliacea (Huds.) Willd. (CME) were studied using WP2, Ames (TA1535 and TA1537), and sister chromatid exchange (SCE) test systems. The results of our studies showed that 5 µM concentration of aflatoxin B1(AFB1) changed the frequencies of SCE and malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx) activities. When 5 and 10 µg/mL concentrations of CME was added to AFB1, the frequencies of SCE and MDA level were decreased and SOD, GSH, and GPx levels were increased. The extract CME did not show any mutagenicity on Ames (Salmonella typhimurium TA1535, TA1537) and WP2 (Escherichia coli) test systems. On the other hand, CME has antimutagenicity on the mentioned test systems. The results of this experiment have clearly shown that CME has a significant antioxidative and antigenotoxic effect, which is thought to be due to the antigenotoxic activities of antioxidant enzymes.
Subject(s)
Antimutagenic Agents/pharmacology , Antioxidants/pharmacology , Biological Products/pharmacology , Lichens/chemistry , Adult , Biological Products/chemistry , DNA Damage/drug effects , Escherichia coli/drug effects , Humans , Leukocytes, Mononuclear/drug effects , Methanol , Oxidoreductases , Salmonella typhimurium/drug effects , Sister Chromatid Exchange/drug effects , Young AdultABSTRACT
The present study is focused on evaluating the antimutagenic properties of Schiff bases and Mn(III) complexes with L-Threonine, L-Serine and L-Tyrosine, which have antimicrobial activity. These six compounds were investigated for antimutagenic properties against Aflatoxin Bi (AFBi) by the micronucleus (MN) assay in a human lymphocyte cell culture in vitro. The protective role of these compounds against AFBi-induced MN is probably related to its doses. A mechanism has been proposed to reduce the effect of AFBi.
Subject(s)
Aflatoxin B1 , Anti-Bacterial Agents , Antidotes , Azo Compounds , Manganese , Serine , Thiosemicarbazones , Threonine , Tyrosine , Aflatoxin B1/antagonists & inhibitors , Aflatoxin B1/toxicity , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antidotes/chemistry , Antidotes/pharmacology , Azo Compounds/chemistry , Azo Compounds/pharmacology , Bacteria/growth & development , Female , Humans , Male , Manganese/chemistry , Manganese/pharmacology , Serine/chemistry , Serine/pharmacology , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology , Threonine/chemistry , Threonine/pharmacology , Tyrosine/chemistry , Tyrosine/pharmacologyABSTRACT
This study was conducted to evaluate the antimutagenic and antimicrobial activities of Schiff bases attached L-glutamine and L-asparagine. Antibacterial activities of the compounds against S. aureus, Sh. dys. typ 7, L. monocytogenes 4b, E. coli, S. typhi H, S. epidermis, Br. abortus, M. luteus, B. cereus, P. putida, and antifungal activity against Candida albicans were studied. These compounds were investigated for antimutagenic properties against Aflatoxin Bi (AFBi) using micronuclei (MN) assay in human lymphocyte cell culture in vitro. The protective role of these compounds against AFBi-induced MN is probably related to its doses.
Subject(s)
Asparagine/chemistry , Asparagine/pharmacology , Glutamine/chemistry , Glutamine/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antimutagenic Agents/chemistry , Antimutagenic Agents/pharmacology , Bacteria/drug effects , Candida albicans/drug effects , Female , Humans , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Manganese/chemistry , Micronucleus Tests , Schiff Bases/chemistryABSTRACT
In this study, the antigenotoxic and antioxidant effects of Cetraria islandica methanol (CME) extract were determined by using sister chromatid exchange (SCE), micronuclei (MN) assays and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) levels against effects of aflatoxin B1 (AFB1) induced oxidative stress and genotoxicity in human lymphocytes in vitro. The results showed that the frequencies of SCE, MN and MDA level decreased, SOD and GPx activities increased when 5 µg/mL and 10 µg/mL doses of CME were added to AFB1-treated cultures. Also, the present results indicate that CME has strong antioxidative and the antigenotoxicity mechanisms of CME are associated with its antioxidant nature.
Subject(s)
Aflatoxin B1/toxicity , Antioxidants/pharmacology , DNA Damage/drug effects , Lichens/chemistry , Lymphocytes/drug effects , Oxidative Stress/drug effects , Adult , Biological Products/pharmacology , Cells, Cultured , Glutathione Peroxidase/blood , Humans , Malondialdehyde/blood , Methanol/pharmacology , Micronucleus Tests , Sister Chromatid Exchange , Superoxide Dismutase/bloodABSTRACT
The aim of this study was to investigate the effects of methanol, acetone, n-hexane and ether extracts obtained from Pseudovernia furfuracea on genotoxicity and total antioxidant capacity (TAC) in cultured human blood cells intoxicated with aflatoxin B(1) (AFB(1)). Sister chromatid exchange (SCE) and micronucleus (MN) tests were used for genotoxic influences estimation. In both the test systems, it was observed that P. furfuracea extracts suppressed the mutagenic effects of AFB(1) due to the type of extracts added to the cultures. Furthermore, a significant reduction in plasma TAC was observed after AFB(1) treatment. Interestingly, the methanol and acetone extracts of the lichen recovered AFB(1)-induced TAC inhibition. The order of extracts of anti-genotoxicity efficacy against AFB(1) was methanol, acetone, ether and n-hexane, respectively. In conclusion, P. furfuracea has been shown to modulate the adverse effects of AFB(1) in human blood cells for the first time.
