ABSTRACT Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases.

Abstract Associations of the activity of the paraoxonase 1 (PON1) enzyme with boar sperm quality still needs to be characterized, since boar ejaculates present distinct portions with differences in sperm concentration and quality. This study evaluated PON1 activity in the serum, in the distinct portions of boar ejaculates and estimated correlations with sperm quality parameters. Ejaculates and blood samples were collected from six boars for three weeks (two per week per boar; n = 36). Serum and post-spermatic portion PON1 activities were positively correlated (P = 0.01) but were both uncorrelated with the PON1 activity in the sperm-rich portion and in the whole ejaculate (P > 0.05). Differences in PON1 activity among boars were only observed in the sperm-rich portion of the ejaculate (P < 0.05). The PON1 activity in the serum and in the post-spermatic portion was generally negatively correlated with parameters of spermatozoa kinetics (P < 0.05). In the sperm-rich portion, PON1 activity was positively correlated with sperm concentration (P < 0.0001), curvilinear distance and velocity (both P < 0.05) and DNA integrity (P < 0.05), but negatively correlated with straightness and linearity (P < 0.05). Thus, boar ejaculates with increased PON1 activity in the sperm-rich portion may present increased concentration and spermatozoa with acceptable curvilinear velocity and distance and DNA integrity, which suggests that PON1 activity may be a biomarker for potential fertility.

ABSTRACT Objectives: Paraoxonase 1 (PON1) is an enzyme that has antioxidant potential, which confers a protective effect against the atherosclerotic process. However, studies associating genetics, dietary patterns and PON1 activity in individuals with cardiovascular disease (CVD) are scarce. Thus, the aim of the current study was to evaluate the influence of dietary factors on serum PON1 in CVD patients. Subjects and methods: Cross-sectional, sub-study of the BALANCE Program Trial. All patients aged 45 years or older and had evidence of established atherosclerotic disease in the preceding 10 years. Body weight, height, waist circumference, blood pressure, lipid profile and fasting glucose were collected. Food intake was assessed with 24-h dietary recall. Data was analyzed using SAS University Edition and a P value ≤ 0.05 was considered statistically significant. Sample was divided into three groups, according to the PON1 T(-107)C genotype (CC, CT and TT) and serum PON1 activity (Low, Medium, High). Results: There were no genotype differences for major factors. However, the systolic blood pressure was lower for CT individuals (p<0.05). Intake of cholesterol, saturated fatty acids (SFA) and monounsaturated fatty acids (MUFAS) was higher in patients with lower PON1 activity. Lipid ingestion tended to be higher in patients with lower PON1 activity (p=0.08). In the multivariate logistic regression model, SFA intake (P=0.03), genotype (P=0.09), gender (P=0.04), age (P=0.07) and carbohydrate intake (P=0.16) contributed the most to the serum PON1 activity. Conclusion: Based on these findings, nutritional guidance for these patients becomes essential, since dietary components interact with serum PON1 activity more than genotype.

ABSTRACT Objective: The aim of this study was to evaluate the serum activity of PON1 in women according to SNPs L55M and T-107C and diet composition. Materials and methods: Blood and serum samples from 26 women were used. DNA extraction, PCR and digestion with restriction enzymes of the PCR fragment were performed for genotyping the PON1 SNPs T-107C and L55M. Serum PON1 activity was measured in a single time point. Patients completed the semi-quantitative food frequency questionnaire and diet composition was estimated. Results: Genotypic distribution for L55M SNP was 56% for the LL genotype, 32% for LM and 12% for MM; for the PON1 C(-107)T SNP it was 28% for the TT genotype, 41% for CT and 31% for CC. Individuals with C and L alleles had higher serum PON1 activity. Combining the two SNPs, we observed that individuals carrying the LL and CC genotypes had twice the activity of carriers of the TT and MM genotypes. Considering food intake, no significant difference was observed between genotypes and intake levels. Conclusion: PON1 T(-107)C and L55M SNPs exert a strong effect on serum PON1 activity in an additive manner and are more important than diet to predict serum PON1 activity.

RESUMO Objetivo Determinar a frequência dos alelos do Human leukocyte antigen e verificar a associação da presença desses alelos com sintomas e outras doenças relacionados à doença celíaca em portadores de doenças autoimunes da tireoide. Métodos Aplicou-se um questionário relacionado aos sintomas e doenças associados à doença celíaca. O ácido desoxirribonucleico genômico foi extraído por meio da coleta das células da mucosa bucal. Os alelos (DQA1*0501; DQB1*0201; DRB1*04) foram identificados por meio da reação em cadeia da polimerase. Resultados Participaram deste estudo 110 portadores de doenças autoimunes da tireoide. Observou-se que 66,4% dos indivíduos carregavam pelo menos um dos alelos estudados e que 58,2% dos indivíduos eram positivos para pelo menos um dos alelos DQ2 (DQA1*0501; DQB1*0201) e destes 18,2% foram positivos para ambos alelos do DQ2(DQA1*0501; DQB1*0201). Com relação ao DQ8 (DRB1*04), 21,8% da população estudada eram positivos para esse alelo e 3,6% eram positivos tanto para o DQ2 (DQA1*0501; DQB1*0201) quanto para o DQ8 (DRB1*04). Foi encontrada associação significativa da presença do alelo DRB1*04 com os sintomas gastrointestinais (p=0,02). Houve associação significativa do alelo DRB1*04 com diabetes mellitus tipo 1 (p=0,02). Conclusão O perfil genético mais fortemente associado à doença celíaca, tais como DQ2 (DQA1*0501; DQB1*0201) e DQ8 (DRB1*04) estavam presentes em torno de 20,0% da população estudada, estes são haplótipos de risco para doença celíaca e principalmente na presença de sintomas e doenças relacionadas à doença celíaca. Sendo assim, é importante realizar o rastreamento para investigar um possível diagnóstico para doença celíaca.

ABSTRACT Objective To determine the frequency of Human leukocyte antigen alleles and to verify the association of the presence of these alleles with symptoms and other diseases related to celiac disease in patients with autoimmune thyroid diseases. Methods A questionnaire on the symptoms and diseases associated with celiac disease was applied. Genomic deoxyribonucleic acid was extracted by collecting cells from the oral mucosa. The alleles (DQA1*0501; DQB1*0201; DRB1*04) were identified by means of the polymerase chain reaction. Results A total of 110 patients with autoimmune thyroid diseases participated in this study. It was observed that 66.4% of the individuals carried at least one of the alleles assessed and that 58.2% of the individuals were positive for at least one of the DQ2 alleles (DQA1*0501; DQB1*0201) and out of these 18.2% were positive for both DQ2 alleles (DQA1*0501; DQB1*0201). With regard to DQ8 (DRB1*04), 21.8% of the studied population was positive for this allele and 3.6% was positive for both DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04). A significant association was found between the presence of the DRB1*04 allele and gastrointestinal symptoms (p=0.02). A significant association of the DRB1*04 allele with type 1 diabetes mellitus (p=0.02) was observed. Conclusion The genetic profiles most commonly associated with celiac disease, such as DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04) were around 20.0% prevalent in the studied population. These are risk haplotypes for celiac disease especially when symptoms and diseases related to celiac disease are present. Therefore, it is important to screen patients to investigate a potential diagnosis for celiac disease.

Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.

Abstract Objective: The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods: This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy-Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results: In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15-30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy-Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions: During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.

Abstract The aim of this study was to evaluate the long-term effects of recombinant bovine somatotropin (rbST) on follicle population and ovulatory follicle development in non-lactating dairy cows. Twenty-one Jersey cows were allocated in rbST (n=11) or control (n=10) groups. On day -60, cows in rbST group received 500 mg of somatotropin (s.c. Lactotropin®, Elanco). On day 0, control and rbST cows received an intravaginal progesterone-releasing device (1.9 g, CIDR®, Zoetis) and GnRH (100 mg, IM, Factrel®, Zoetis). On day 8, cows received PGF2α (25 mg, IM, Lutalyse®, Zoetis) and the CIDR® was removed. Twelve hours after device removal (D8), serum, follicular fluid and granulosa cells samples were collected. Serum and follicular concentration of estradiol (E2) and progesterone (P4) were analyzed. Total RNA was extracted from granulosa cells to measure gene expression of LHCGR, STAR, HSD-3B1, CYP11A1, CYP19A1, CYP17A1, IGFR and PAPPA by real-time PCR. Ultrasonography was performed on days -60, -53, -46, -14, -7, 0 and 8 for antral follicle count. Results were analyzed by repeated measures ANOVA and t-test. There was no effect of rbST treatment on the number of follicles during the 60 days period, as well as no effect on serum and follicular fluid E2 and follicular fluid P4 at the moment of follicle aspiration. There was a reduction in PAPPA (P = 0.006), CYP11A1 (P = 0.04) and CYP19A1 (P = 0.002) mRNA levels in granulosa cells of the pre-ovulatory follicle of rbST treated cows. In conclusion, a single dose of rbST did not have long-term effects on antral follicle population, serum and follicular E2/P4 concentrations in non-lactating dairy cows. Despite that, rbST injection decreased granulosa cell expression of genes related to steroidogenesis in the pre-ovulatory follicle.

ABSTRACT Studies have shown that drinks containing Ilex paraguariensis extract can promote many benefits in animals and in humans. The present study aimed to evaluate in vivo effects of Ilex paraguariensis extract on metabolic profile, obesity prevention and expression of genes related with adipogenesis and lipogenesis in Wistar female rats fed a high-fat diet. For this experiment 32 Wistar female rats with normal weight were used and randomly separated into four groups: diet (standard or high-fat) and treatment (water or Ilex paraguariensis extract) for 34 days. The rats receiving Ilex paraguariensis extract had lower body weight compared to the control group in both diets. Likewise, there was a reduction in triglycerides in the groups fed high-fat diet and treated with Ilex paraguariensis extract. The creatinine levels were lower in the groups treated with Ilex paraguariensis and in high-fat diet. It was observed an increased liver gene expression for Fas and Scd1 in the group treated with hyperlipid diet + Ilex paraguariensis. It can be concluded that Ilex paraguariensis extract decreased body weight gain in both control and high-fat diets, reduced plasma triglycerides and creatinine levels and increased liver expression of genes related to lipogenesis.

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

ABSTRACT Neutropenia is one of the adverse effects caused by the administration of chemotherapy drugs. The present study aimed at investigating the effect of vitamin C supplementation in a model of immunosuppression induced by cyclophosphamide in mice. Vitamin C supplementation (50 mg/kg/day) administered intraperitoneally (i.p.) for 7 consecutive days in adult Swiss albino female. Mice were divided into four groups (n= 8/group): 1. Control (only distilled water i.p.), 2. Cyclophosphamide group (cyclophosphamide i.p. 150 and 100 mg/kg on days 1 and 4, respectively and distilled water daily), 3. Vitamin C group (Vitamin C 50 mg/kg i.p. and distilled water daily), and 4. Cyclophosphamide and Vitamin C group (cyclophosphamide i.p. 150 and 100 mg/kg on days 1 and 4, respectively and vitamin C 50 mg/kg i.p. daily). Vitamin C did not interfere in leukocytes count, but when co-administered with cyclophosphamide, significant interaction was observed, intensifying the neutropenia caused by cyclophosphamide. Vitamin C did not influence body weight during treatment, but groups receiving cyclophosphamide had a significant weight loss from the third day of treatment until the end of experiment compared to the control group. Vitamin C supplementation intensified neutropenia induced by cyclophosphamide and did not prevent weight loss induced by cyclophosphamide in mice.

RESUMEN La neutropenia es uno de los efectos adversos causados por la administración de medicamentos de quimioterapia. El presente estudio tuvo como objetivo investigar el efecto de la administración de suplementos de vitamina C en un modelo de inmunosupresión inducida por ciclofosfamida en ratones. Se realizó la suplementación de vitamina C (50 mg/kg/día) administrada por vía intraperitoneal (i.p) por 7 días en ratones hembras swiss albinas adultas. Los ratones fueron divididos en cuatro grupos (n= 8 / grupo): Control (solamente agua destilada i.p) Ciclofosfamida (ciclofosfamida i.p. 150 mg/kg y 100 mg/kg en el día 1 y día 4 y agua destilada diariamente) Vitamin C (vitamina C 50 mg/kg i.p y agua destilada diariamente), Ciclofosfamida y Vit C (ciclofosfamida i.p. 150 y 100 mg/kg en el día 1 y día 4 y vitamina C 50 mg/kg i.p. diariamente). La vitamina C por sí no interfirió en los valores de leucocitos y tampoco influyó en el peso corporal durante el tratamiento, pero los grupos que recibieron ciclofosfamida tuvieron una pérdida de peso significativa desde el tercer día de tratamiento hasta el final del experimento en comparación con el grupo control. La suplementación de vitamina C intensificó la neutropenia inducida por ciclofosfamida y no evitó la pérdida de peso inducida por ciclofosfamida en ratones.

RESUMO: O objetivo desse estudo foi estimar a soroprevalência da neosporose e os possíveis fatores de risco em rebanhos (Bos taurus taurus) localizados na mesorregião Noroeste do Rio Grande do Sul, Brasil. Foram coletadas 322 amostras de sangue de bovinos leiteiros, em 18 propriedades localizadas em 17 munícipios desta mesorregião. Um questionário epidemiológico foi aplicado em cada propriedade, contendo questões relacionadas às características gerais dos rebanhos, dados reprodutivos e manejo animal. As amostras de soro foram testadas através do teste de imunoensaio enzimático (ELISA) para Neospora caninum. Os resultados demonstraram uma soroprevalência de Neospora de 88,9% (16/18) entre os rebanhos e 31,1% (100/322) entre os indivíduos. Entre os fatores de risco analisados foi observado que descarte por problemas reprodutivos (OR=0,6), presença de áreas alagadiças (OR=0,5) e venda comercial (OR=0,4) estavam associados a soroprevalência. No entanto, a compra de animais substituídos no rebanho desempenhou um papel significativo na ocorrência da doença (OR=2,2). Os resultados desse estudo sugerem que o Neospora caninum esteve presente nos rebanhos estudados, bem como, existem fatores associados com a soroprevalência nas propriedades da mesorregião do Noroeste do Rio Grande do Sul.

ABSTRACT: The aim of this study was to estimate neosporosis seroprevalence and its associated risk factors in milk herds (Bos taurus taurus) located in the northwestern region of Rio Grande do Sul State, Brazil. Three hundred twenty-two blood samples were collected from dairy cows on 18 farms in 17 cities of this region. An epidemiologic questionnaire was completed for each farm. It consisted of questions about the general characteristics of the herd, reproduction, and animal management. Serum samples were tested for Neospora caninum using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Results indicated a seroprevalence of Neospora in 88.9% (16/18) of herds and 31.1% (100/322) of individuals. Risk factor analyses demonstrated that culling by reproductive disorder (OR = 0.6), flooding (OR = 0.5), and commercial sale (OR = 0.4) were associated with seroprevalence. Nevertheless, the purchase of replacement animals in the herd played an important role in disease occurrence (OR = 2.2). Results of this study suggested that Neospora caninum was present in the studied herds under investigation and that there are risk factors associated with its seroprevalence on the farms of the northwestern of Rio Grande do Sul.

RESUMO: Estudos anteriores avaliaram o efeito de diferentes procedimentos reprodutivos sobre marcadores de desconforto em bovinos e ovinos. Tais estudos podem estimular a adoção de técnicas que preservem o bem-estar animal. Entretanto, os marcadores comumente utilizados apresentam alta influência de fatores externos. Para contornar isso, a avaliação conjunta de diferentes parâmetros sistêmicos pode ser utilizada para determinar com maior precisão a presença de estresse, dor ou inflamação, como cortisol, proteínas de fase aguda, a bradicinina e a substância P. O objetivo desta revisão é relacionar potenciais marcadores de inflamação e estresse, discutindo como e quando são regulados frente aos estímulos em bovinos e ovinos. Ainda, pretende-se revisar de que forma procedimentos reprodutivos com diferentes graus de invasividade acarretam em desconforto, fornecendo informações para a elaboração de estratégias que possibilitem minimizá-lo.

ABSTRACT: Previous studies have evaluated the effects of different reproductive procedures on discomfort markers in sheep and cattle. Such studies may help stimulate the adoption of techniques that are more beneficial for animal welfare. However, markers that are commonly used to evaluate discomfort are highly influenced by external factors. To overcome this, several systemic markers can be evaluated to more precisely identify stress, pain, and inflammation. Such markers include cortisol, acute phase proteins, bradykinin, and substance P. We aimed to review the potential markers of stress, pain, and inflammation, and discuss how and when they are regulated after different stimuli related to reproductive procedures in cattle and sheep. Furthermore, we aimed to review how reproductive procedures with different degrees of invasiveness cause stress and provide information that may help develop strategies to limit animal discomfort.

ABSTRACT This study aimed to evaluate the effect of Ilex paraguariensis infusion on redox state of Wistar rats submitted to high-fat and standard diet. Glutathione determination and lipid peroxidation in the hippocampus tissues and liver was performed, as well as the analysis of gene expression of superoxide dismutase, catalase and glutathione peroxidase by real-time polymerase chain reaction. The results from hippocampus showed that the groups fed with standard diet exhibited significant reduction of lipid peroxidation when supplemented with Ilex paraguariensis. The analysis from glutathione determination in the hippocampus showed a significant increase in glutathione activity in the group treated with high-fat diet and Ilex paraguariensis. In the liver, results showed no significant difference in both glutatione and lipid peroxidation analisys. Gene expression of superoxide dismutase, catalase and glutathione peroxidase showed that there was significant difference in the groups treated with high-fat diet and Ilex paraguariensis. In summary, the Ilex paraguariensis showed substantial potential for antioxidant activities.

RESUMO Objetivo: Investigar os efeitos da vitamina C sobre níveis de peroxidação lipídica e glutationa reduzida em tecido hepático de camundongos imunossuprimidos por ciclofosfamida. Métodos: O estudo foi realizado em camundongos Swiss, fêmeas, com 45 dias de idade, separados em quatro grupos com oito animais cada. Grupos: controle (água destilada), vitamina C (50 mg/kg), ciclofosfamida (100 + 150 mg/kg) e tratamento (vitamina C 50 mg/kg + ciclofosfamida 100 +150 mg/kg). Todas as aplicações foram via intraperitoneal. O ensaio biológico teve duração de seis dias, sendo o sétimo a eutanásia dos animais. As análises bioquímicas de peroxidação lipídica (quantificação de substâncias reativas ao ácido tiobarbitúrico) e glutationa reduzida (estimativa de tiois não proteicos) foram realizadas em tecido hepático. Resultados: A ciclofosfamida causou aumento significativo (p<0,0001) nos níveis de peroxidação lipídica. Não foram observadas alterações significativas nos grupos tratados com vitamina C. A ciclofosfamida por si só, não alterou níveis de glutationa reduzida. A vitamina C causou a redução do nível de glutationa reduzida em relação ao controle tanto nos animais que receberam ciclofosfamida quanto nos que não receberam. No entanto, nos grupos tratados com o quimioterápico houve uma interação entre a droga e a vitamina, ou seja, o quimioterápico intensificou a diminuição da glutationa reduzida provocada pela vitamina C. Conclusão: A ciclofosfamida, na dose e período utilizados, foi capaz de induzir o dano oxidativo verificado pelo aumento da peroxidação lipídica. A vitamina C, na dose de 50 mg/kg de peso, não apresentou potencial para proteger contra o dano oxidativo provocado pelo quimioterápico.

ABSTRACT Objective: To investigate the effects of vitamin C supplementation on the levels of lipid peroxidation and reduced glutathione in the liver tissue of mice immunosuppressed with cyclophosphamide. Methods: Thirty-two 45-day-old female Swiss mice were divided into four groups of eight animals each as follows: control (distilled water); vitamin C (50 mg/kg); cyclophosphamide (100 + 150 mg/kg); and treatment (vitamin C 50 mg/kg + cyclophosphamide 100 +150 mg/kg). The substances were provided intraperitoneally for six days, and on the seventh day, the mice were euthanized. The biochemical analyses of lipid peroxidation (quantification of thiobarbituric acid-reactive substances) and reduced glutathione (estimate of non-protein thiols) were performed on liver tissue. Results: Cyclophosphamide increased the levels of lipid peroxidation (p<0.0001). Significant changes were not found in the groups treated with vitamin C. Cyclophosphamide alone did not affect the levels of reduced glutathione. Compared with the control group, vitamin C reduced the levels of reduced glutathione in animals that received or not cyclophosphamide. Vitamin C interacted with cyclophosphamide, that is, the chemotherapeutic agent further decreased the lower levels of reduced glutathione secondary to vitamin C intake. Conclusion: Cyclophosphamide, in the study dosage and duration, was capable of inducing oxidative damage, verified by increased lipid peroxidation. A vitamin C dosage of 50mg/kg of body weight did not protect against the oxidative damage caused by the chemotherapeutic agent.

The objective of this study was to evaluate the influence of the ovulatory follicle diameter on the reproductive performance of lactating beef cows subjected to low progesterone fixed-time artificial insemination (FTAI) protocols. Ninety-three lactating beef cows (60-80 days postpartum) at random stages of estrous cycle were given a luteolytic dose of prostaglandin F2α (500 μg cloprostenol; PGF) twice, 11 d apart. Ten days after the second PGF treatment, cows were given 1.5 mg of estradiol benzoate im and a progesterone-releasing intravaginal device (Cue-Mate) with a single pod containing 0.78 g progesterone (Day 0). Cows received another luteolytic dose of PGF on Day 0. On Day 8, the Cue-Mate was removed. Fifty-four to 56 hours later, cows received 12.5 mg of porcine LH (pLH) i.m. and were concurrently artificially inseminated. Ultrasound examinations of the ovaries were performed on Days 10 and 17 to evaluate the diameter of ovulatory follicle and corpus luteum, respectively. Cows which presented ovulatory follicle > 19 mm resulted in larger corpus luteum than cows that had ovulatory follicle <15 mm in diameter. However, cows with ovulatory follicle between 13-15 mm had higher pregnancy rate than other categories of ovulatory follicle. Although larger ovulatory follicles result in larger corpus luteum and consequently higher progesterone production, the optimal size of ovulatory follicles (13-15 mm) may result in positive benefits on pregnancy rate for cows subjected to FTAI with low progesterone concentration protocols.