It can break apart to yield hydroxyl radicals that attack important biochemicals like proteins and DNA. To protect itself, the body makes catalase, the enzyme that decomposes hydrogen peroxide before it can form hydroxyl radicals. Actually, the formation of hydrogen peroxide in cells is an attempt by the body to protect itself from an even more dangerous substance, superoxide.
Oxygen is a double-edged sword. Still, it does present a risk and this is where catalase enters the picture. It breaks the peroxide down into oxygen and water. And that is why hydrogen peroxide foams when poured onto liver. If you have ever used hydrogen peroxide to disinfect a cut, you may have also noted some bubbling since blood can decompose hydrogen peroxide into oxygen and water. He reasoned that if an unknown stain caused foaming on treatment with hydrogen peroxide, it probably contained hemoglobin, and was therefore likely to be blood.
Introduced in , this was the first presumptive test for blood. But since hydrogen peroxide tends to decompose slowly by itself, looking for extra bubbles was a challenging endeavour. This relied on the chemistry of phenolphthalein, well-known today to students as an acid-base indicator. Phenolphthalein is colourless in acid but turns a deep pink in a basic solution.
In this case, though, the important feature is that phenolphthalein can be reduced with zinc into colourless phenolphthalin, which along with a base is present in the test reagent. In the usual process, a drop of alcohol is added to an unknown stain to dissolve any hemoglobin that may be present, followed by rubbing with a swab that has been treated with the Kastle-Meyer reagent.
A drop of hydrogen peroxide is then applied to the swab. Interestingly, however, evolutionary modifications within the family Trypanosomatidae have resulted in the absence of the gene in T. Elimination of this gene could be related to the environment within the host since T. It may be that an ascorbate-dependent antioxidant defence during infection is more crucial for T.
The unique antioxidant defence system in trypanosomatids is based on the low-molecular-weight thiol T SH 2 , which maintains the intracellular environment in a reduced state essentially by the action of T SH 2 reductase. Further pathways, which are coupled with the T SH 2 cycle and catalysed by tryparedoxin peroxidase and APX, are responsible for the subsequent detoxification of hydrogen peroxide to water. Previous studies by our group have shown that the levels of expression of cytosolic and mitochondrial tryparedoxin peroxidases are increased in populations of T.
The present study has demonstrated that APX expression is increased in T. A one-electron reduction leads to nitro-anion radical formation and its re-oxidation in the presence of oxygen leads to the formation of non-toxic BZ and ROS Moreno et al. Although this detoxifies the drug, it also generates toxic superoxide anion radicals. The enzyme iron-superoxide dismutase TcFeSOD removes this anion, leading to the production of hydrogen peroxide that is then converted to water molecules by tryparedoxin peroxidase and APX.
Interestingly, our group has shown that these three enzymes are over-expressed in the population of T. An alternative hypothesis that could correlate the overexpression of these enzymes with T. It has been shown that the incomplete inhibition of NADH-fumarate reductase by BZ might transfer electrons to stronger oxidants, as molecular oxygen, producing superoxide anions Turrens et al.
The mechanism of drug resistance, such as that to BZ, is often complex and multi-factorial, involving different pathways. Recently, it has been described in the literature that the key step involved in the BZ activation is catalysed by a type I NTR Wilkinson et al. In addition, our present and previous data show that the resistant parasites also overexpress enzymes involved in the antioxidant defence TcFeSOD, tryparedoxin peroxidase and APX , thus detoxifying the parasite and making it BZ-resistant.
The results obtained show that the expression of TcAPX protein is increased by treatment with exogenous hydrogen peroxide, indicating that TcAPX expression can be induced by oxidative stress. These findings suggest that resistant parasites may use APX to overcome oxidative stress, a hypothesis that is in agreement with the present results demonstrating that levels of expression of TcAPX are higher in BZ-resistant T. In this context, it has previously been observed that, following exposure to exogenous hydrogen peroxide, populations of T.
Interestingly, L. Thus, Dolai et al. Increased transcription of APX has also been observed in cultured soybean cells that had been treated with exogenous hydrogen peroxide Lee et al. In the present study, two TcAPX transcripts, one of 2. However, the results from Western blot analyses revealed that the expression levels of TcAPX protein were two and three-fold higher in T. Cells can develop resistance to oxidative stress by increasing the expression of genes that encode enzymes involved in antioxidant defence and repair systems Steenkamp , Finzi et al.
Consideration of the results from our present and previous studies Nogueira et al. In addition, we have shown that BZ-resistant parasites are more tolerant of exogenous hydrogen peroxide than their susceptible counterparts and can modulate TcAPX expression in response to cellular levels of the peroxide, thus protecting themselves against lethal damage.
It is concluded that the absence of APX in mammals and its importance in the antioxidant defence system of trypanosomatids make this enzyme a rational target for chemotherapy against Chagas disease. Abrir menu Brasil. Abrir menu. Trypanosoma cruzi; drug resistance; ascorbate peroxidase; hydrogen peroxide. Key words: Trypanosoma cruzi - drug resistance - ascorbate peroxidase - hydrogen peroxide Chagas disease is a potentially life-threatening zoonosis whose etiological agent is the flagellate protozoan Trypanosoma cruzi.
Deficient metabolic utilization of hydrogen peroxide in Trypanosoma cruzi Biochem J : Trypanothione-dependent peroxide metabolism in Trypanosoma cruzi different stages. Mol Biochem Parasitol 61 : American trypanosomiasis also known as Chagas Disease. Available from: cdc. Ascorbate variations and dehydroascorbate reductase activity in Trypanosoma cruzi epimastigotes and trypomastigotes. Mol Biochem Parasitol 66 : Docampo R Sensitivity of parasites to free radical damage by antiparasitic drugs.
Chem Biol Interact 73 : Localization of peroxidase activity in Trypanosoma cruzi microbodies. Experientia 32 : Docampo R, Moreno SN Free radical metabolites in the mode of action of chemotherapeutic agents and phagocytic cells on Trypanosoma cruzi Rev Infect Dis 6 : Leishmania major ascorbate peroxidase overexpression protects cells against reactive oxygen species-mediated cardiolipin oxidation. Free Radic Biol Med 45 : Bootstrap confidence levels for phylogenetic trees.
Comparative genomics of trypanosomatid parasitic protozoa. Science : Filardi LS, Brener Z Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease.
Trans R Trop Med Hyg 81 : Trypanosoma cruzi response to the oxidative stress generated by hydrogen peroxide. Mol Biochem Parasitol : Glutathione and trypanothione in parasitic hydroperoxide metabolism.
Free Radic Biol Med 27 : Profiling gene transcription reveals a deficiency of mitochondrial oxidative phosphorylation in Trypanosoma cruzi -infected murine hearts: implications in chagasic myocarditis development. Biochim Biophys Acta : Insights into the redox biology of Trypanosoma cruzi : trypanothione metabolism and oxidant detoxification.
However, recently published method for recombinant hSPO production offers new tools for those investigations. Abstract Human whole saliva contains two peroxidases, salivary peroxidase hSPO and myeloperoxidase hMPO , which are part of the innate host defence in oral cavity. Publication types Research Support, Non-U.
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