Einleitung: Es ist wenig darüber bekannt, wie sich das antioxidative System von Kälbern nach der Geburt entwickelt, welche Faktoren darauf Einfluss nehmen und wie sich antioxidative Parameter in ihren Aktivitäten resp. Konzentrationen unter physiologischen Bedingungen verändern. Zielstellung: Ziel dieser Arbeit war es zum einen die altersabhängige Entwicklung antioxidativer Parameter bei gesunden Kälbern und Jungrindern bis zum 18. Lebensmonat zu verfolgen und zum anderen zu evaluieren, ob bei metabolisch gering belasteten Jungrindern jahreszeitliche Differenzen bezüglich Superoxiddismutase (SOD), Glutathionperoxidase (GPX) und Trolox Equivalent Antioxidative Capacity (TEAC) bestehen. Material und Methoden: Es wurden gesunde weibliche Kälber bzw. Jungrinder der Rasse Holstein Friesian / Deutsche Schwarzbunte aus drei Betrieben am 1. (n = 33) und 7. (n = 31) Tag sowie im 1. (n = 33), 3. (n = 33), 6. (n = 5), 9. (n = 5), 12. (n = 32) und 18. (n = 31) Monat post natum (p. n.) klinisch und labordiagnostisch untersucht. Weiterhin wurden in einem Betrieb während eines Jahres im September, November, Januar, März, Mai und Juli jeweils 6 gesunde weibliche Jungrinder, die zum Untersuchungszeitpunkt 12 Monate alt waren, kontrolliert. Die Tiere wurden im Stall in Anbindehaltung gehalten, ausgenommen der im Mai in Weidehaltung untersuchten Tiere. Analysiert wurden im Blut die antioxidativen Parameter SOD, GPX und TEAC, der Hämatokrit (Hkt) und die Stoffwechselparameter Gesamtprotein, Albumin, Bilirubin, Haptoglobin, Harnstoff, Cholesterol, ß-Hydroxybutyrat (BHB), AST, AP, GLDH, CK, Ca, anorganisches Phosphat (Pi) und Fe. Ergebnisse: Ein betrieblicher Einfluss war statistisch nicht nachweisbar. Vom 1. Tag bis zum 18. Monat p. n. zeigten die antioxidativen Parameter SOD, GPX und TEAC einen gleichartigen Verlauf mit einem kontinuierlichen Anstieg bis zum 6. Monat p. n.. Die GPX-Aktivitäten stiegen von 50-80 U/ml Hkt am 1. Tag p. n. auf 100-190 U/ml Hkt im 6. Monat p. n. an. Die niedrigsten Aktivitäten (p<0,05) bestanden am 1. und 7. Tag (62-90 U/ml Hkt) p. n.. Die SOD-Aktivitäten am 1. (4500-5600 U/g Hb) und 7. Tag (4600-5450 U/g Hb) p. n. waren niedriger als im 1. (5400-6800 U/g Hb) und 3. Monat (5600-7800 U/g Hb) p. n. (p<0,05). Der Anstieg der TEAC-Konzentration vom 1. Tag p. n. (220-290 µmol/l) zum 6. Monat p. n. (260-340 µmol/l) war nicht signifikant. Nach dem 6. Monat p. n. fielen die Akti-vitäten resp. Konzentrationen ab, wobei die SOD-Aktivitäten mit 12 (4000-5000 (U/g Hb) und 18 Monaten (3700-5000 U/g Hb) p. n. signifikant niedriger waren als im 1. und 3. Mo-nat p. n.. Die GPX-Aktivitäten lagen mit 12 (118-152 U/ml Hkt) und 18 Monaten (105-150 U/ml Hkt) p. n. signifikant über denen der ersten Lebenswoche. Die TEAC-Konzentrationen waren im 12. Monat p. n. mit 260-320 µmol/l größer als vom 1. Tag bis zum 1. Monat (240-280 µmol/l) p. n. (p<0,05). Die SOD, GPX und TEAC korrelierten außer mit 9 Monaten p. n. zu allen Untersuchungszeitpunkten signifikant positiv. Für AST, AP, CK und Bilirubin wurden am 1. Tag p. n. die signifikant höchsten Aktivitäten resp. Konzen-trationen ermittelt, für Haptoglobin am 7. Tag p. n.. Gesicherte Korrelationen bestanden zwischen Albumin, Bilirubin und der TEAC, zwischen BHB und TEAC, GPX sowie SOD außerdem zwischen Ca und Pi. Im Jahresverlauf waren die GPX-Aktivitäten im September und Januar mit 73-103 U/ml Hkt niedriger als von März bis Juli mit 104-142 U/ml Hkt (p<0,05). Erniedrigte TEAC-Konzentrationen wurden besonders im Januar (272-302 µmol/l) und signifikant im März (265-299 µmol/l) gegenüber September und November (319-345 µmol/l) ermittelt. Die SOD-Aktivitäten differierten nicht gesichert. GPX und SOD korrelierten im ganzen Jahr gesichert, TEAC und SOD außer im Januar ebenfalls, GPX und TEAC nur im November, März, Mai und Juli. Die Stoffwechselparameter befanden sich im physiologischen Bereich, mit Ausnahme von Harnstoff im November und Juli sowie Pi im Mai. Schlussfolgerungen: Es wird geschlussfolgert, dass das antioxidative System der neu-geborenen Kälber zur Geburt noch unreif ist und sich bis zum sechsten Monat p. n. stabilisiert. Die durch den Abbau des fetalen Hämoglobins und die Vormagenentwicklung vermehrt entstehenden ROS tragen zu einer weiteren Aktivitäts- resp. Konzentrationssteigerung der antioxidativen Parameter bis zu einem Maximum im 6. Monat p. n. bei. Danach stellt sich ein Gleichgewicht zwischen Pro- und Antioxidantien ein. Auf die GPX-Aktivitäten und TEAC-Konzentrationen konnte ein jahreszeitlicher Einfluss bei Jungrinden ermittelt werden.

Doctor of Philosophy / Department of Horticulture, Forestry, and Recreation Resources / Jack D. Fry / ‘Meyer’ zoysiagrass (Zoysia japonica Steud.) has been the predominant cultivar in the transition zone of the U.S. since its release in 1952, primarily because of its good freezing tolerance. However, it is slow to establish and recover after sod harvest, and has poor shade tolerance. I evaluated ‘Meyer’, some commonly used cultivars, and 18 progeny from crosses of ‘Emerald’ (Z. japonica × Z. tenuifolia Willd. ex Thiele) × Z. japonica or Z. matrella (L.) Merr. × Z. japonica for stolon growth characteristics; sod tensile strength and recovery after harvest; shade resistance; freezing tolerance and its relationship to autumn color retention; and the potential influence of dehydrin and chitinase gene expression in freezing tolerance. After planting vegetative plugs, rates of stolon initiation (r = 0.66 in 2007, r = 0.94 in 2008) and elongation (r = 0.66 in 2007, r = 0.53 in 2008) were positively correlated (P < 0.05) with zoysiagrass coverage. At 60 days after sod harvest, recovery growth coverage ranged from 17% to 97% and a progeny from Z. matrella × Meyer (97% coverage) demonstrated superior sod recovery growth to Meyer (38% coverage). Under 68% silver maple (Acer saccharinum L.) tree shade, stolon number was reduced 38 to 95% and stolon length 9 to 70% compared to turf in full sun. Several progeny from crosses between Emerald or a Z. matrella x Z. japonica produced more and/or longer stolons than Meyer in the shade, suggesting potential for increased shade tolerance. Autumn color in October and November, 2007 was positively correlated (r = 0.44 and r = 0.58, P < 0.01) with the lethal temperature killing 50% of tillers (LT50) in December, 2007. All grasses except Cavalier and one progeny were equivalent to Meyer in freezing tolerance with LT50s ranging from -0.2 to -12.2 oC. Dehydrin-like (11.9, 23, 44.3, and 66.3 kDa) and chitinase (26.9 kDa) gene expression increased with cold acclimation and was similar among all grasses. In general, some new zoysiagrass progeny exhibited superior growth and/or stress tolerances compared to Meyer, which bodes well for potential release of a new cultivar for use in the transition zone.

La superoxyde dismutase à Manganèse (SOD Mn ou SOD2) est une enzyme importante dans la défense antioxydante, qui semble jouer un rôle mal défini dans le développement des tumeurs selon l’expression constitutive de son gène. Cependant, les mécanismes de régulation de cette expression constitutive sont mal connus, en particulier dans les cellules tumorales mammaires. Ce travail a reposé sur la mise en évidence préalable d’une protéine, appelée la Damaged DNA Binding 2 (DDB2) protein, se fixant spécifiquement sur la région promotrice du gène SOD2. La DDB2 est connue pour sa participation dans la réparation de l’ADN par excision de nucléotides. Dans un 1er temps, nous avons caractérisé la séquence d’ADN spécifiquement reconnue dans la région proximale du promoteur du gène SOD2, sur laquelle la DDB2 s’y fixe sous la forme d’un monomère, pour réguler négativement la transcription constitutive de la SOD Mn dans les cellules tumorales mammaires non métastatiques de type MCF-7. Par ailleurs, la DDB2 n’est pas impliquée dans le mécanisme d’induction du gène SOD2, lorsque les cellules MCF-7 sont exposées à des substances inductrices. En revanche, nous avons montré que l’absence de la protéine DDB2, associée à celle du facteur de transcription AP-2?, déjà connu comme répresseur du gène SOD2, entraîne une expression constitutive élevée de la SOD Mn dans les cellules tumorales mammaires métastatiques n’exprimant pas le récepteur aux œstrogènes (ER-). De plus, cette expression constitutive élevée est principalement dépendante du facteur de transcription Sp1. Dans un 2ème temps, nous avons évalué la signification biologique de la régulation de l’expression constitutive de la SOD Mn par la DDB2 dans les cellules tumorales mammaires. Nos résultats montrent que la DDB2 active la prolifération des cellules tumorales mammaires ER+, en exerçant sa régulation négative sur l’expression de la SOD Mn. Dans un 3ème temps, nous avons cherché à montrer les conséquences sur la croissance des cellules tumorales mammaires ER-, qui surexpriment naturellement la SOD Mn. Nos résultats révèlent que l’enzyme antioxydante joue un rôle important dans les mécanismes moléculaires impliqués dans le pouvoir invasif des cellules tumorales mammaires ER-. La surexpression de la SOD Mn, associée à un taux faible des enzymes éliminant l’H2O2, entraînent une augmentation du pouvoir invasif déjà élevé des cellules tumorales mammaires ER-, associée une augmentation de l’activité de la métalloprotéinase 9. L’élimination, en présence d’antioxydants, de l’H2O2 libéré par l’activité de la SOD Mn surexprimée, entraîne une inhibition à la fois de la croissance et des capacités invasives des cellules tumorales mammaires ER-. L’ensemble de ce travail contribue à mieux comprendre l’importance de la SOD Mn et du mécanisme de régulation de son gène dans la croissance et l’invasion tumorales. Ainsi ce travail révèle également la SOD Mn et la DDB2 comme de potentiels facteurs prédictifs de la progression tumorale mammaire. Enfin, la découverte de la nouvelle activité biologique de la DDB2 ouvre un vaste champ de perspectives intéressantes en cancérologie mammaire. / Manganese superoxide dismutase (Mn SOD or SOD2) is an important enzyme in the antioxidizing defence, which seems to play an unclear role in the cancer development, according to the constitutive expression of its gene. However, the regulation of this constitutive expression is not totally known, particularly in the breast cancer cells. This work is based on a preliminary revealing that a protein, called Damaged DNA Binding 2 (DDB2), specifically binds the SOD2 gene promoter. The DDB2 is known for its involvement in the nucleotide excision repair. At first step, we characterized the specific DNA sequence recognized in the proximal area of the SOD2 gene promoter, on which a DDB2 monomer binds, in order to regulate negatively the Mn SOD transcription in the MCF-7 non metastatic breast cancer cells. Besides, DDB2 is not involved in the mechanism of SOD2 gene induction, when MCF-7 cells are exposed to induced substances. However, we showed that the lack of the DDB2 protein, associated with the lack of the AP-2a transcription factor, already known as a repressor of the SOD2 gene, lead to a high Mn SOD constitutive expression in the metastatic breast cancer cells. Furthermore, this high constitutive expression is mainly dependent of the Sp1 transcription factor. Secondly, we estimated the biological meaning of the regulation of the Mn SOD constitutive expression by the DDB2 in the breast cancer cells. Our results show that the DDB2 activates the positive ER breast cancer cell proliferation, by exercising its negative regulation on the Mn SOD expression. Thirdly, we tried to show the consequences on the negative ER breast cancer cell growth, which naturally and highly express the Mn SOD. Our results reveal that the antioxidizing enzyme plays an important role in the molecular mechanisms involved in the invasive capacities of the negative ER breast cancer cells. The high Mn SOD expression, associated in a decrease of the H2O2 detoxifying enzymes expression, enhance the negative ER breast cancer cell invasion and an increase of the matrix metallopeptidase-9 activity. The H2O2 elimination, with specific antioxidants, decreases both negative ER breast cancer cell growth and invasive capacities. This whole work contributes to better understand the Mn SOD importance and the mechanism of its gene regulation, in the tumoral growth and invasion. This work also reveals the Mn SOD and DDB2 as potential predictive factors of the breast cancer progress. Finally, the discovery of this new DDB2 biological activity opens a huge field of interesting perspectives in breast cancer research.

"Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to dementia in adults. The mechanism of neurodegeneration is thought to involve the extracellular production of a highly toxic A-beta peptide that engages cell surface receptors to induce cellular oxidative stress and apoptosis, but the signal transduction pathways that lead to A-beta induced cell death are unknown. We previously showed that a human ependymin neurotrophic peptide mimetic (hEPN-1) can promote cell survival in an in vitro AD model system. This initial observation was extended in this thesis by investigating the mechanism of A-beta induced apoptosis and hEPN-1 induced survival. Immunoblots were used to assay the total cellular levels of specific caspase proteins. The results show that A-beta induced apoptosis uses an extrinsic caspase pathway involving caspases-2 and -3, and that hEPN-1 treatment can reduce those caspase levels. A caspase activity assay showed that A-beta increased caspase-3/7 activity, while hEPN-1 treatment lowered it. Moreover, in vivo studies with AD transgenic mice showed that hEPN-1 treatment increased antioxidative superoxide dismutase levels in brain. Thus, hEPN-1 holds potential as a therapeutic to treat the underlying neurodegenerative cause of AD, not merely its symptoms as with other currently approved AD drugs."

Ependymin (EPN) is a goldfish brain neurotrophic factor (NTF) previously shown to function in a variety of cellular events related to long-term memory formation and neuronal regeneration. Because of these functions, EPN and other NTFs have potential applications for treating neuro-degenerative conditions, including stroke. In previous experiments, our lab in collaboration with Victor Shashoua of Ceremedix Inc (Boston, MA), designed short synthetic peptide CMX-8933 (a proteolytic cleavage product of EPN) and CMX-9236 (an EPN-Calmodulin combination peptide) that mimic the action of full-length EPN. In a rat stroke model, administration of these peptides i.v. significantly lowered brain ischemic volume (Shashoua et al., 2003). Because oxidative stress is one of the primary mediators of cell damage following a stroke, we hypothesized that NTFs, and in particular our therapeutic peptides, may act in part by reducing neuronal oxidative stress. Thus, the purpose of this thesis was to determine whether CMX-8933 and CMX-9236 increase the cellular titers of anti-oxidative enzymes. A hybridization array was used as a“hypothesis generator" to obtain candidates for further analysis. This approach applied to rat primary brain cortical cells treated with CMX-8933 identified superoxide dismutase (SOD) as strongly upregulated. SOD immunoblots on whole cell lysates, and RT-PCR on total cellular RNA, were used to confirm this observation. In time-course and dose-response experiments, treatment of rat primary cortical cultures with either peptide showed an optimal 8.5 fold (N = 5, p < 0.001) increase in SOD protein, while administration of CMX-8933 to murine neuroblastoma cells caused a 6.5 fold (N = 3, p = 0.001) increase in SOD mRNA levels. Previous work in other laboratories indicated that systemic (i.v.) administration of full-length NTFs allows only an inefficient delivery across the blood brain barrier (BBB). We hypothesized that our short synthetic peptides may cross the BBB more efficiently. Immunoblot analysis of brains and hearts excised from mice treated i.v. with various doses of CMX-8933 confirmed the elevated SOD titers (10 fold in brain, and 8 fold in heart, at a 6 mg/kg dose for 5 hr; N = 5, p < 0.001). Furthermore, we hypothesized that conjugation of CMX-8933 to BBB carrier DHA, a natural neuronal membrane fatty acid shown previously to enhance the delivery of dopamine to the brain (Shashoua and Hesse, 1996), might further enhance the NTF therapy. Delivery of DHA-8933 increased SOD expression by 3 fold (N = 4, p < 0.001) relative to non-conjugated CMX-8933. Recently, the use of special incubators that allow the culture of cells under low oxygen conditions (anoxia) has been used as an in vitro model for stroke. When we tested our peptides in this new in vitro model, surprisingly SOD was upregulated 3 fold (N = 3, p = 0.003) in rat primary cortical cells cultured for 24 hr under oxygen deprivation, compared to normoxic conditions. This implies that these rat cultures may have an endogenous cellular system for responding to oxygen stress, a finding worthy of further investigation. Treatment of anoxic cells with CMX-8933 increased SOD levels another 2.8 fold (N = 3, p < 0.001) compared to the levels for anoxia alone (for a total of 8.5 fold relative to normoxic cells). Altogether, the data from this thesis illustrate that small NTF EPN peptide mimetics increase the cellular titers of the mRNA and protein for the anti-oxidative enzyme SOD, which may be an important step in their known therapeutic benefits.

<p>Sarcoptes scabiei is a disease-causing parasitic mite of humans and animals that is prevalent worldwide. The parasite lives in burrows in the epidermis of its host. These burrows are formed by a combination of mechanical destruction by the mite and secretion of various factors.</p><p>The enzyme superoxide dismutase (SOD) catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such, it is an important antioxidant defense in nearly all cells exposed to oxygen. In this project, the enzyme was expressed in transformed Escherichia coli cells. The SOD cDNA from S. scabiei was ligated into two different expression vectors: pPU16 and pET-14b. The S. scabiei SOD open reading frame reported here is 696 nucleotides long and yields a protein with a molecular weight of  69.5 kDa. Only one of the constructs was successfully created, using pPU16. The construct was designated pPU110 and has a sequence coding for a hexahistidine tag downstream of the SOD cDNA and has a sequence coding for the maltose binding protein (MBP) upstream.</p><p>The expression plasmid pPU110 was verified by DNA-sequencing and the tested in different expression experiments. Analysis using SDS-PAGE showed that recombinant fusion SOD could be readily expressed in E.coli.</p>

Sarcoptes scabiei is a disease-causing parasitic mite of humans and animals that is prevalent worldwide. The parasite lives in burrows in the epidermis of its host. These burrows are formed by a combination of mechanical destruction by the mite and secretion of various factors. The enzyme superoxide dismutase (SOD) catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such, it is an important antioxidant defense in nearly all cells exposed to oxygen. In this project, the enzyme was expressed in transformed Escherichia coli cells. The SOD cDNA from S. scabiei was ligated into two different expression vectors: pPU16 and pET-14b. The S. scabiei SOD open reading frame reported here is 696 nucleotides long and yields a protein with a molecular weight of  69.5 kDa. Only one of the constructs was successfully created, using pPU16. The construct was designated pPU110 and has a sequence coding for a hexahistidine tag downstream of the SOD cDNA and has a sequence coding for the maltose binding protein (MBP) upstream. The expression plasmid pPU110 was verified by DNA-sequencing and the tested in different expression experiments. Analysis using SDS-PAGE showed that recombinant fusion SOD could be readily expressed in E.coli.

No description available.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome of unknown etiology that most commonly affects people in middle and high age. The hallmark of ALS is a progressive and simultaneous loss of upper and lower motor neurons in the central nervous system that leads to a progressive muscle atrophy, paralysis and death usually by respiratory failure. ALS is not a pure motor neuronal syndrome; it extends beyond the motor system and affects extramotor areas of the brain as well. The majority of the patients suffer from a sporadic ALS disease (SALS) while in at least ten percent the disease appears in a familial form (FALS). Mutations in the gene encoding the antioxidant enzyme superoxide dismutase-1 (SOD1) are the most common cause of FALS. More than 165 SOD1 mutations have been described, and these confer the enzyme a cytotoxic gain of function. Evidence suggests that the toxicity results from structural instability which makes the mutated enzyme prone to misfold and form aggregates in the spinal cord and brain motor neurons. Recent studies indicate that the wild-type human SOD1 protein (wt-hSOD1) has the propensity to develop neurotoxic features. The aim of the present study was to investigate if wt-hSOD1 is involved in the pathogenesis of SALS and FALS patients lacking SOD1 mutations and to evaluate the neurotoxic effect of misfolded wt-hSOD1 protein in vivo by generating a transgenic wt-hSOD1 mice model. We produced specific SOD1-peptide-generated antibodies that could discriminate between the misfolded and native form of the enzyme and optimized a staining protocol for detection of misfolded wt-hSOD1 by immunohistochemistry and confocal microscopy of brain and spinal cord tissue. We discovered that aggregates of misfolded wt-hSOD1 were constitutively present in the cytoplasm of motor neurons in all investigated SALS patients and in FALS patients lacking SOD1 gene mutations. Interestingly, the misfolded wt-hSOD1 aggregates were also found in some motor neuron nuclei and in the nuclei of the surrounding glial cells, mainly astrocytes but also microglia and oligodendrocytes, indicating that misfolded wt-hSOD1 protein aggregates may exert intranuclear toxicity. We compared our findings to FALS with SOD1 mutations by investigating brain and spinal cord tissue from patients homozygous for the D90A SOD1 mutation, a common SOD1 mutation that encodes a stable SOD1 protein with a wild-type-like enzyme activity. We observed a similar morphology with a profound loss of motor neurons and aggregates of misfolded SOD1 in the remaining motor neuron. Interestingly, we found gliosis and microvacuolar degeneration in the superficial lamina of the frontal and temporal lobe, indicating a possible frontotemporal lobar dementia in addition to the ALS disorder. Our morphological and biochemical findings were tested in vivo by generating homozygous transgenic mice that over expressed wt-hSOD1. These mice developed a fatal ALS-like disease, mimicking the one seen in mice expressing mutated hSOD1. The wt-hSOD1 mice showed a slower weight gain compared to non-transgenic mice and developed a progressive ALS-like hind-leg paresis. Aggregates of misfolded wt-hSOD1 were found in the brain and spinal cord neurons similar to those in humans accompanied by a loss of 41 % of motor neurons compared to non-transgenic litter mates. In conclusion, we found misfolded wt-hSOD1 aggregates in the cytoplasm and nuclei of motor neurons and glial cells in all patients suffering from ALS syndrome. Notable is the fact that misfolded wt-hSOD1 aggregates were also detected in FALS patients lacking SOD1 mutations indicating a role for SOD1 even when other genetic mutations are present. The neurotoxicity of misfolded wt-hSOD1 protein was confirmed in vivo by wt-hSOD1 transgenic mice that developed a fatal ALS-like disease. Taken together, our results support the notion that misfolded wt-hSOD1 could be generally involved and play a decisive role in the pathogenesis of all forms of ALS.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-06-15T00:21:54Z No. of bitstreams: 1 RomuloRodrigoDeSouzaAlmeida_DISSERT.pdf: 1782048 bytes, checksum: b2c3f99e10e637474fe9a749a13cc2be (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-06-17T23:35:49Z (GMT) No. of bitstreams: 1 RomuloRodrigoDeSouzaAlmeida_DISSERT.pdf: 1782048 bytes, checksum: b2c3f99e10e637474fe9a749a13cc2be (MD5) / Made available in DSpace on 2016-06-17T23:35:49Z (GMT). No. of bitstreams: 1 RomuloRodrigoDeSouzaAlmeida_DISSERT.pdf: 1782048 bytes, checksum: b2c3f99e10e637474fe9a749a13cc2be (MD5) Previous issue date: 2015-07-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / V?rios estudos tem estabelecido uma associa??o entre Diabetes Mellitus tipo 1 altera??es hep?ticas estresse oxidativo. No entanto os conhecimentos de como essas altera??es ocorrem no sistema antioxidante ainda n?o est? elucidado. Este estudo avaliou os efeitos de quatro semanas de diabetes tipo 1 no tecido hep?tico. Ratos machos wistar foram divididos em 2 grupos: Controle (C) e Diab?tico (D). A an?lise da atividade de enzimas antioxidantes (CAT e SOD); a express?o do mRNA de CAT, SOD1, SOD2, GPX1 e PRX4 foram avaliadas; marcadores de estresse oxidativo tamb?m foram avaliados (Peroxida??o de lip?deos, carbonila??o de prote?nas e conte?do tiol) e conte?do de H2O2 hep?tico. Como resultado a diabetes aumentou a atividade da SOD e a express?o g?nica da SOD2, enquanto diminuiu a express?o da SOD1. Assim como houve diminui??o da atividade da CAT e na express?o g?nica da CAT, GPX1 e PRX4. Houve tamb?m mudan?as em biomarcadores de estresse oxidativo. Nossos resultados sugerem que provavelmente as quatro semanas da diabetes, induzem altera??es precoces no sistema antioxidante no f?gado de ratos induzidos por STZ, agravando altera??es decorrentes do estresse oxidativo levando a forma??o de esp?cies reativas de oxig?nio, podendo contribuir para um preju?zo da fun??o hep?ticas. / The correlation between the type 1 diabetes mellitus and oxidative stress have been described in several studies, however its underlying mechanisms are not fully elucidated. The present work aimed to evaluate the effects of four weeks of streptozootocin-induced (STZ) diabetes in the redox homeostasis of rat hepatocytes. Thus, the liver of male Wistar rats from control and diabetic groups were collected and the activity and expression of antioxidant enzymes, as well the main markers of oxidative stress and content of H2O2 in these tissues were measured. The diabetes induced the activity of superoxide dismutase (SOD) and the gene expression of its mitochondrial isoform, SOD2. However, the expression of SOD1, the cytoplasmic isoform, was reduced by this disease. The activity and expression of catalase (CAT), as well the expression of glutathione peroxidase 1 (GPX1) and peroxiredoxin 4 (PRX4) were drastically reduced in the hepatocytes of diabetics rats. Even with this debility in the peroxidases mRNA expression, the content of H2O2 was reduced in the liver of diabetics rats when compared to the control group. The diabetes caused an increase of lipid peroxidation and a decrease of protein thiol content, showing that this disease causes distinct oxidative effects in different cell biomolecules. Our results indicate that four week of diabetes induced by STZ is already enough to compromise the enzymatic antioxidant systems of the hepatocytes.