Insights Into Antioxidant Strategies to Counteract Radiation-Induced Male Infertility.

Significance: Radiotherapy, which employs ionizing radiation to destroy or prevent the multiplication of tumor cells, has been increasingly used in the treatment of neoplastic diseases, especially cancers. However, radiation collaterally leads to prolonged periods of sperm count suppression, presumably due to impaired spermatogenesis by depleting the germ cell pool, which has long-term side effects for male reproduction. Recent Advances: Studies of antioxidant compounds as a potential strategy for male fertility preservation have been performed mainly from animal models, aiming to prevent and restore the male germinal tissue and its function, particularly against the oxidative stress effects of radiation. Evidence in preclinical and clinical trials has shown that inhibitors of the renin-angiotensin system and other drugs, such as statins and metformin, are candidates for ameliorating radiation-induced damage to several tissues, including the testis and prostate. Critical Issues: Research for developing an ideal radioprotective agent is challenging due to toxicity in the normal tissue, tumor radioresistance, cellular response to radiation, costs, regulation, and timeline development. Moreover, male radioprotection experiments in humans, mainly clinical trials, are scarce and use few individuals. This scenario is reflected in the slow progress of innovation in the radioprotection field. Future Directions: Expanding human studies to provide clues on the efficacy and safety of radioprotective compounds in the human reproductive system is necessary. Drug repurposing, frequently used in clinical practice, can be a way to shorten the development pipeline for innovative approaches for radioprotection or radiomitigation of the repercussions of radiotherapy in the male reproductive system.

Losartan Attenuates Radiation-Induced Damage on Testes and Accelerates Tubular Regeneration.

Male germ cells are particularly susceptible to radiation; infertility being a common consequence after radiotherapy as it impairs spermatogenesis. This study aimed to test whether treatment with losartan (LOS), a selective antagonist of angiotensin II receptor subtype 1 (AT1R), can prevent or attenuate the acute and long-term radiation-induced damage to testes. Wistar rats were randomly distributed into six groups, three of which were studied on day 2 after irradiation: control (CTRL 2), irradiated non-treated (IR 2), and irradiated and treated with LOS (IRLOS 2); and three other groups that were studied on day 60 after irradiation: control (CTRL 60), irradiated non-treated (IR 60), and irradiated and treated with LOS (IRLOS 60). Seven consecutive days before and on the day of irradiation with 2.5 Gy directly administered in the scrotum, the animals were treated with LOS (34 mg/kg/two times/day). This treatment was continued 2 or 60 days after irradiation. The sperm quality was assessed from epididymis cauda. In addition, the testes were submitted to histopathological and morphometric-stereological analysis as well as the proliferating cell nuclear antigen (PCNA) quantification. Serum FSH and LH and plasma testosterone levels were also determined. The data obtained 2 days after the irradiation showed germ cell apoptosis, formation of vacuoles in the seminiferous epithelium, sloughing of germ cells into the lumen, and retention and phagocytosis of step-19 spermatids in Sertoli basal cytoplasm. The treatment with LOS in this period did not prevent or attenuate a radio-induced damage to the testes, illustrating that this drug does not protect against apoptosis derived from direct effects of radiation. On the other hand, 60 days after exposure, the data evidenced the deleterious effects of ionizing radiation on the testes as decreasing of testicular, epididymal, and seminal vesicle masses; tubular atrophy; reduction of cellular proliferation; and loss of germ cells. LOS was able to prevent some of those deleterious effects, promoting improvements in seminal vesicle mass, sperm vitality, plasma testosterone levels, vacuole number, and cell proliferation. In conclusion, inhibition of the AngII/AT1R axis by LOS is effective in protecting the indirect/delayed radiation damage resulting from oxidative stress established in the tissue.

Orchiectomy but not adjuvant-induced arthritis induces structural modifications in rat aortas.

PURPOSE: This study aimed to verify whether Adjuvant-Induced Arthritis (AIA) and/or Orchiectomy (ORX) modify the expression of the Nox1, Nox2 and Nox4 isoforms, the endothelial function or the structure of rat aortas. METHODS: Sixty-three Wistar rats were distributed into four groups: 1) Control; 2) ORX; 3) AIA; 4) Orchiectomy plus to Arthritis-induction (ORX/AIA). Thus, 21 days after the onset of AIA (by intradermal injection of Mycobacterium tuberculosis), the presence of Nox1, Nox2 and Nox4, the acetylcholine (ACh)-induced relaxation and the media layer thickness were assessed in the aorta taken from these animals. RESULTS: The Nox1, Nox2 and Nox4 were immunostained in intima, media and adventitia layers of aortas taken from all studied groups and AIA apparently increased this immunostaining. These modifications of Nox1, Nox2 or Nox4 expression, however, were not confirmed by Western blotting. In addition, neither AIA nor ORX changed the endothelial function, but ORX increased the media layer thickness in the studied aortas. CONCLUSION: The present study showed weak clues of increased expression of Nox1, Nox2 and Nox4 as a result of AIA, as well as of Nox1 reduction caused by ORX. In addition, the endothelial function was not modified in the aortas of these animals by both AIA and/or ORX. On the other hand, ORX increased significantly the aorta media layer thickness in the studied animals, which was apparently mitigated by AIA.

Influence of galantamine in the inflammatory process and tissular lesions caused by Trypanosoma cruzi QM2 strain.

INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS: For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.

Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat.

Renal injury induced by rheumatoid arthritis is not clear and may be related to the angiotensin II. We aim to investigate the adjuvant-induced arthritis (AIA) injury in rat kidney, focusing the angiotensin II/AT1 pathway. Male Wistar rats were allocated in to three groups: Control, AIA and AIA plus losartan. The AIA was induced by injection of 100 µL of an emulsion of dissected Mycobacterium tuberculosis (50 mg/mL) on the paw. Treatment with losartan was initiated on the first day of immunization (daily subcutaneous injection, 1 mg/kg). After 60 days post immunization, we evaluated kidney function by plasma creatinine, urea and uric acid levels and creatinine depuration; kidney injury by apoptosis analysis and inflammation markers such as macrophages, transforming growth factor beta (TGF-ß) and inducible nitric oxide synthase (iNOS) expression; oxidative stress by plasma thiobarbituric acid reactive substances (TBARS); renal expression of angiotensin receptors subtype 1 (AT1 ) and 2 (AT2 ) and plasma concentration of angiotensin II. AIA rats showed elevated plasma levels of creatinine, urea, uric acid, TBARS and Ang II and reduced creatinine depuration, and enhanced kidney macrophage number, TGF-ß, caspase-3, iNOS and AT1 /AT2 receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF-ß and iNOS in renal tissues, and reduced plasma TBARS. We conclude that AIA causes kidney injury by a physiopathological mechanism that involves AT1  stimulation in renal tissue, elevating the presence of macrophages, the expression of TGF-ß and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.

Exercise-Induced Modulation of Angiotensin II Responses in Femoral Veins From 2-Kidney-1-Clip Hypertensive Rats.

The present study investigated the angiotensin II (Ang II) responses in rat femoral veins taken from 2-kidney-1clip (2K1C) hypertensive rats at 4 weeks after clipping, as well as the effects of exercise on these responses. In this manner, femoral veins taken from 2K1C rats kept at rest or exposed to acute exercise or to exercise training were challenged with Ang II or endothelin-1 (ET-1) in organ bath. Simultaneously, the presence of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined in these preparations by western blotting. In these experiments, femoral veins exhibited subdued Ang II responses. However, after nitric oxide (NO) synthesis blockade, the responses were higher in the femoral veins taken from animals kept at rest [0.137(0.049-0.245); n = 10] than those obtained in trained animals kept at rest [0.008(0.001-0.041); n = 10] or studied after a single bout of exercise [0.001(0.001-0.054); n = 11]. In preparations in which, in addition to NO synthesis, both the local production of prostanoids and the action of ET-1 on type A (ETA) or B (ETB) receptors were inhibited, the differences induced by exercise were no longer observed. In addition, neither ET-1 responses nor the presence of COX-1 and COX-2 in these preparations were modified by the employed exercise protocols. In conclusion, NO maintains Ang II responses reduced in femoral veins of 2K1C animals at rest. However, vasodilator prostanoids as well as other relaxing mechanisms, activated by ETB stimulation, are mobilized by exercise to cooperate with NO in order to maintain controlled Ang II responses in femoral veins.

Academic research challenges in Brazil and its impairment by COVID-19 pandemic: a medical students point of view / O impacto da pandêmica COVID-19 na iniciação científica brasileira: ponto de vista de estudantes de medicina

ABSTRACT: Background: The COVID-19 pandemic and its control measures, which have not been experienced in the world in the last hundred years, have impacted academic scientific production, which, in Brazil, was already in the process of progressive erosion of its foundations. Thus, scientific initiation during medical graduation, which depends on funding and institutional structure, and extremely beneficial to the graduation process, was jeopardized due to restrictive measures. Objective: This article aims to expose the point of view of undergraduate medical students enrolled in a scientific initiation program about the panorama of Brazilian academic scientific production and the impact of the COVID-19 pandemic in its multiple aspects. Discussion: The lack of an effective scientific initiation is one of the many factors that lead to a decline in the number of medical researchers. The way that scientific initiation is placed, as part of a parallel curriculum, and a whole scrapped public production structure are impairing, chronic and noteworthy features. The apparatus of national scientific production is mostly structured in Higher Education Institutions and research institutions, both public. Within the scope of graduation, it can be didactically subdivided into four pillars: financial support, structure, student proactivity and the advisor's aptitude. The COVID-19 pandemic has been an additional blow to this weakened and fragile structure. Scientific initiation was thus negatively impacted. Public opinion and political aspects further influence an imbroglio of "scientific denial" and a craving for effective information and solutions to the unprecedented problem of a pandemic of this proportion. Conclusion: It is clear that national scientific production is placed in a survival situation in the face of new challenges posed by the pandemic. Likewise, scientific initiation is less and less stimulating during graduation, even though it is an experience of great value in medical and personal development. (AU)

RESUMO: Introdução: A pandemia pelo COVID-19 e suas medidas de controle, não vivenciadas no mundo nos últimos cem anos, impactou a produção científica acadêmica, a qual, no Brasil, já se encontrava em processo de erosão progressiva de seus alicerces. Por conseguinte, a iniciação científica durante a graduação, extremamente benéfica na formação médica, que é dependente de fomento e estrutura institucional, sofreu um impacto negativo com as medidas restritivas. Objetivo: O artigo discorre em um ponto de vista de estudantes de medicina, envolvidos em pesquisas, acerca do panorama da produção científica acadêmica brasileira e o impacto perante a pandemia COVID-19 em seus múltiplos aspectos. Discussão: A falta de uma iniciação científica efetiva é um dos muitos fatores que levam ao declínio do número de médicos pesquisadores. Nesse ínterim, o modo como a iniciação científica está inserida, como parte de um currículo paralelo, e toda uma estrutura de produção pública sucateada são aspectos danosos, crônicos e dignos de nota. O aparato de produção científica nacional é majoritariamente estruturado nas instituições de ensino superior e institutos de pesquisa, ambas públicas. No âmbito da graduação, pode ser didaticamente subdividido em quatro pilares: fomento, estrutura, proatividade do estudante e aptidão do orientador. A pandemia do COVID-19 tem sido um golpe adicional a essa estrutura debilitada e frágil. A iniciação científica foi, com isso, negativamente impactada. A opinião pública e aspectos políticos influenciam adicionalmente em um imbróglio de "negacionismo científico" e anseio por informações e soluções eficazes para o problema inédito de uma pandemia dessa proporção. Conclusão: Percebe-se que produção científica nacional é colocada numa situação de sobrevivência diante de novos desafios postos pela pandemia. Da mesma forma, a iniciação científica é cada vez menos estimuladora durante a graduação, apesar de ser uma experiência de grande valor na formação médica e pessoal. (AU)

Influence of galantamine in the inflammatory process and tissular lesions caused by Trypanosoma cruzi QM2 strain

Abstract INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.

Exercise training attenuates angiotensin II-induced vasoconstriction in the aorta of normotensive but not hypertensive rats.

NEW FINDINGS: What is the central question of this study? What are the effects of exercise on Ang II-induced vasoconstriction in aortas of normotensive rats and how do these effects occur in two-kidney-one-clip hypertensive animals? What is the main finding and its importance? In two-kidney rats, exercise training improves the Ang II-induced vasoconstriction by endothelium-derived NO released through AT2 R activation. This effect of exercise training on the Ang II-induced vasoconstriction is blunted in two-kidney-one-clip hypertensive animals, possibly as a consequence of oxidative stress. ABSTRACT: This study investigated the effects of both acute exercise and training on the Ang II-induced vasoconstriction in aorta of normotensive (two-kidney; 2K) and two-kidney-one-clip (2K1C) hypertensive rats, focusing on endothelial mechanisms related to nitric oxide (NO) and prostanoids. Aorta rings of 2K and 2K1C male Wistar rats, sedentary and trained, killed at rest and after acute exercise, were challenged with Ang II in either the absence or the presence of PD 123,319, a selective angiotensin receptor subtype 2 (AT2 R) antagonist; Nω -nitro-l-arginine methyl ester (l-NAME), a non-selective inhibitor of nitric oxide synthase; indomethacin, a non-selective inhibitor of cyclooxygenase; or Tiron, an analogue of superoxide dismutase. Aortas of sedentary and trained animals studied at rest were also submitted to histomorphometric analysis. Exercise training reduced the Ang II-induced vasoconstriction in aorta of 2K but not of 2K1C animals. This reduction of Ang II response in aortas of 2K animals was not found after endothelial removal or treatment with PD 123,319 or l-NAME. These results suggest that exercise training improves the modulation of Ang II-induced vasoconstriction in aorta of 2K animals, by endothelium-derived NO released due to the activation of AT2 R. No exercise-induced change of Ang II response occurred in 2K1C animals, except in the presence of Tiron, which was evidence for reduction of such responses only in resting trained 2K1C animals. In 2K1C animals, NO modulation of Ang II-induced vasoconstriction might be suppressed by local oxidative stress. Moreover, exercise training slightly reduced the media layer thickness in the aortas of the 2K1C, but not 2K animals, which may indicate cardiovascular protection of these animals.

Plasma antioxidant substances apparently do not influence the radiodermatitis occurrence / Substâncias antioxidantes do plasma aparentemente não influenciam a ocorrência de radiodermatite

AIMS: Radiation affects not only tumors but also healthy tissues through the increment of oxidative stress. Thus, this study aimed to evaluate the oxidative stress degree as well as non-enzymatic antioxidant defenses in the plasma of patients submitted to radiotherapy and to verify if these parameters are modified in those patients who develop radiodermatitis. METHODS: Forty-one patients submitted to radiotherapy for treatment of breast cancer were followed. From these patients, plasma samples were obtained at the beginning, in the middle and at the end of the treatment, for analysis of thiobarbituric acid reactive substances (TBARS) and ferric reducing ability of plasma (FRAP). RESULTS: No significant differences were observed in terms of TBARS and FRAP in plasma harvested from these patients at the beginning and at the middle of the treatment. There was lower incidence of grade two radiodermatitis among patients undergoing radiotherapy with hypofractionated doses. There were no differences in FRAP or TBARS among patients who developed radiodermatitis of any degree in relation to those who did not develop this side effect. No differences of FRAP or TBARS were observed between patients that presented grade two radiodermatitis regarding to the others studied. CONCLUSION: There was no clear relationship between changes in TBARS or FRAP with the occurrence or severity of radiodermatitis.

Effects of Green and Ripe Coffee in the Metabolic Profile and Muscle Enzymes in Animals Practicing Physical Exercise.

Many studies have shown that plants can be therapeutic alternatives in the prevention or treatment of various diseases. Among these, green coffee may present different pharmacological effects related to the regulation of glycemia and lipid metabolism and is related to the prevention of cardiovascular diseases. The objective of our study was to evaluate the effects of using green and ripe coffee on the metabolic profile and muscular enzymes after the practice of physical exercises in Wistar rats. We included six groups: G1 (control group), G2 (group submitted to swimming), G3 (group that consumed green coffee), G4 (group that consumed green coffee and was submitted to swimming), G5 (group that consumed ripe coffee), and G6 (group that consumed ripe coffee and was submitted to swimming). Our results showed that there was a significant reduction in the percentage of visceral fat in G3, G5, and G6. We did not observe significant modifications in glycemia, lipids, lactate dehydrogenase, ferric reducing ability of plasma, and ferric-xylenol orange. The levels of creatine phosphokinase showed a reduction in the groups G2 and G4. No significant differences were found in the atherogenic indices. There is a global demand for natural compounds that can be safe, cheap, related to minimum side effects, and provide health benefits. Our results show that the use of green or ripe coffee may contribute to reduce the percentage of visceral fat and consequently may protect against further complications once this tissue produces proatherogenic hormones. Furthermore, green coffee may play a role in protecting muscle injury after the practice of physical exercises.

Influence of the AT1 Receptor Antagonists Telmisartan and Losartan on Reproduction and Offspring After Paternal Exposure to Ionizing Radiation.

This study evaluated the repercussions of paternal exposure to radiation on reproduction and offspring in rats, as well as whether treatment with the angiotensin II type 1 (AT1) receptor antagonists telmisartan and losartan has a mitigating effect. Rats were randomly divided into 6 groups: control, radiation, telmisartan, losartan, radiation + telmisartan, and radiation + losartan. A single 5 Gy dose of radiation was administered directly into the scrotum, followed by treatment with telmisartan (12 mg/kg/d) or losartan (34 mg/kg/2 times per day) for 60 days in the groups receiving these medications. The reproductive ability of the test animals was assessed before and after exposure to radiation via fertility tests. The resulting offspring were analyzed for the presence of external and internal anomalies. Ionizing radiation significantly affected the rates of fertility, pre- and postimplantation losses, and implantation. Telmisartan and losartan did not significantly prevent this radiation-induced damage. The frequency of fetal anomalies was similar in offspring produced before and after paternal radiation exposure. Moreover, irradiated rats that received treatments and were able to generate offspring did not produce fetuses with morphological changes; this may represent a possible radioprotective effect AT1 antagonists have on offspring development, although few fetuses survived and were evaluated for malformations. Although the study findings indicate that these medications have a positive effect, further studies with longer treatment periods (extending beyond 1 rat spermatogenic cycle) are needed to determine whether these drugs significantly improve reproductive rates after paternal exposure to radiation, which may also reflect an increase in the number of viable fetuses.

Oxidative stress among informal caregivers / Estresse oxidativo em cuidadores informais

ABSTRACT OBJETIVE: to evaluate oxidative stress and non-enzymatic antioxidant defenses in informal caregivers, and correlations with anxiety, health satisfaction and quality of life. METHOD: a case-control analytical study was performed, where the case was represented by the main informal caregiver and the control was paired with individuals with identical characteristics to the case, but who were not informal caregivers. The following instruments were used: a sociodemographic questionnaire, the Beck anxiety scale and the WHOQoL-Bref. Oxidative stress was measured through blood by analysis of the Ferric Reducing Ability of Plasma (FRAP) and Thiobarbituric Acid Reactive Substances (TBARS) markets. RESULTS: most informal caregivers were females. There was no difference in the degree of anxiety between the Case and Control groups. Among informal caregivers, 9.4% said they were very dissatisfied and 53.1% dissatisfied with their health. Most caregivers (43.8%) rated their quality of life as poor and 12.5% ​​as very poor, while most controls rated it as good (68.8%). The TBARS and FRAP values ​​were lower in the Case group than in the Control group. CONCLUSION: The informal caregivers, who were mostly women, defined themselves as dissatisfied or very dissatisfied with their health. Nevertheless, they did not manifest a higher degree of anxiety in comparison with the control population. In addition, they presented a lower degree of oxidative stress than the non-caregiving participants, perhaps due to a greater mobilization of the non-enzymatic antioxidant defenses present in the body.

OBJETIVO: Avaliar o estresse oxidativo e as defesas antioxidantes não enzimáticas em cuidadores informais, comparando os dados obtidos com indivíduos não cuidadores, correlacionando ao grau de ansiedade, satisfação com a saúde e qualidade de vida. MÉTODO: Estudo analítico caso-controle, onde o caso é representado pelo cuidador informal principal e o controle é pareado por indivíduos com características idênticas ao caso, exceto pelo fato de não desempenhar o papel de cuidador informal. Instrumentos utilizados: questionário sociodemográfico, escala de ansiedade de Beck e WHOQOL-bref. O estresse oxidativo foi medido por meio do sangue, com marcadores Ferric Reducing Ability of Plasma (FRAP) e Thiobarbituric Acid Reactive Substances (TBARS). Resultados: O cuidador informal é representado em sua maioria por indivíduos do sexo feminino. Não houve diferença no grau de ansiedade entre os grupos caso e controle. Dentre os cuidadores informais, 9,4% disseram estar muito insatisfeitos e 53,1% insatisfeitos com sua saúde. Referente à qualidade de vida, a maioria dos cuidadores (43,8%) classificou como ruim e 12,5% como muito ruim, enquanto a maior parte dos controles a classificou como boa (68,8%). Os valores de TBARS e FRAP foram menores no grupo caso em relação ao grupo controle. CONCLUSÃO: O cuidador informal, em sua maioria mulheres, se definem insatisfeitos ou muito insatisfeitos com sua saúde. Apesar disso, não manifestaram grau de ansiedade maior em relação à população controle. Apresentaram grau de estresse oxidativo menor em relação aos participantes não cuidadores, talvez, devido a maior mobilização das defesas antioxidantes não enzimáticas presentes no organismo.

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver.

PURPOSE: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. METHODS: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. RESULTS: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. CONCLUSIONS: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver

Abstract Purpose: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. Methods: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. Results: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. Conclusions: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion.

INTRODUCTION: Ischemia-reperfusion (IR) injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN) might attenuate IR renal injury. OBJECTIVE: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. METHODS: Male Wistar rats were distributed into six groups (N=6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR) and maintained until animal sacrifice (48h after surgery). We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. RESULTS: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. CONCLUSION: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress.

Prior intake of Brazil nuts attenuates renal injury induced by ischemia and reperfusion / A ingestão prévia de castanha-do-brasil atenua a lesão renal induzida por isquemia e reperfusão

ABSTRACT Introduction: Ischemia-reperfusion (IR) injury results from inflammation and oxidative stress, among other factors. Because of its anti-inflammatory and antioxidant properties, the Brazil nut (BN) might attenuate IR renal injury. Objective: The aim of the present study was to investigate whether the intake of BN prevents or reduces IR kidney injury and inflammation, improving renal function and decreasing oxidative stress. Methods: Male Wistar rats were distributed into six groups (N=6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily and individually for 7 days before surgery (SHAM or IR) and maintained until animal sacrifice (48h after surgery). We evaluated the following parameters: plasma creatinine, urea, and phosphorus; proteinuria, urinary output, and creatinine clearance; plasmatic TBARS and TEAC; kidney expression of iNOS and nitrotyrosine, and macrophage influx. Results: Pre-treatment with 75 mg of BN attenuated IR-induced renal changes, with elevation of creatinine clearance and urinary output, reducing proteinuria, urea, and plasmatic phosphorus as well as reducing kidney expression of iNOS, nitrotyrosine, and macrophage influx. Conclusion: Low intake of BN prior to IR-induced kidney injury improves renal function by inhibition of macrophage infiltration and oxidative stress.

RESUMO Introdução: a lesão por isquemia-reperfusão (IR) resulta, entre outros fatores, de inflamação e estresse oxidativo. Devido às suas propriedades anti-inflamatórias e antioxidantes, a castanha-do-brasil (BN) pode atenuar a lesão renal causada por IR. Objetivo: O objetivo foi investigar se a ingestão prévia de BN reduz a lesão e a inflamação renal causadas por IR, melhorando a função renal e o estresse oxidativo. Métodos: Ratos Wistar machos foram distribuídos em seis grupos (N=6/grupo): SHAM (controle), SHAM tratado com 75 ou 150 mg de BN, IR, e IR tratado com 75 ou 150 mg de BN. O procedimento de IR consistiu na nefrectomia à direita e oclusão da artéria renal esquerda por 30 minutos. A castanha foi administrada diariamente e individualmente por sete dias antes da cirurgia (SHAM ou IR), e mantida até o sacrifício (48h pós-cirurgia). Os seguintes parâmetros foram avaliados: creatinina, ureia e fósforo plasmáticos; proteinúria, volume urinário e depuração de creatinina; TBARS e TEAC (capacidade antioxidante) plasmáticos; expressão renal de iNOS e nitrotirosina, e influxo de macrófagos. Resultados: O pré-tratamento com 75 mg de BN atenuou os parâmetros de função renal alterados pela IR, com elevação da depuração de creatinina e o volume urinário, redução da proteinúria, ureia e fósforo plasmáticos, e diminuição da expressão de iNOS, nitrotirosina e da infiltração de macrófagos. Conclusão: A ingestão de baixa quantidade de BN, previamente ao processo de IR, melhora a função renal pela inibição da infiltração de macrófagos e do estresse oxidativo.

Effects of telmisartan and losartan on irradiated testes.

AIMS: To analyze the effects of radiation on the reproductive tissue of male Wistar rats and to evaluate whether treatment with the Ang II AT1 receptor antagonists telmisartan and losartan mitigate the dysfunctions resulting from this exposure. MAIN METHODS: Rats were randomly divided into groups: Control, Irradiated, Telmisartan, Losartan, Irradiated+Telmisartan, and Irradiated+Losartan. Single dose of 5Gy was administered directly into the scrotum, followed by treatment with telmisartan (12mg/kg/day) or losartan (34mg/kg/two times/day) for 60days. Testicular function parameters were evaluated from spermatozoa of the vas deferens. Testes were processed for histopathological and morphometric-stereological analysis. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was evaluated. KEY FINDINGS: Radiation significantly reduced sperm motility, concentration, vitality, and increased the number of abnormal spermatozoa. Telmisartan and losartan did not significantly prevent these radiation-induced disorders. Seminiferous tubules were atrophied in both untreated and treated irradiated testes, and exhibited vacuoles, increased interstitial tissue and high number of blood vessels. However, several seminiferous tubules in recuperation were founded among damaged tubules in the testes of treated animals. The PCNA immunohistochemistry confirmed these outcomes. PCNA-positive cells were detected in dividing spermatogonia and spermatocytes from irradiated telmisartan and losartan treated rats whereas in the only-irradiated group, PCNA staining was observed in the nuclei of only the surviving spermatogonia. SIGNIFICANCE: Under these experimental conditions, the testicular function parameters showed that radiation produced marked damage that was not reversed by treatments. However, gonadal restructuring and recovery of spermatogenesis in treated animals may to reflect attenuation of radiation-induced damages and potential start of recovery.

Dipteryx alata Vogel May Improve Lipid Profile and Atherogenic Indices in Wistar Rats Dipteryx alata and Atherogenic Indices.

Worldwide prevalence of noncommunicable chronic degenerative diseases is among the main causes of death worldwide. The consumption of some foods such as nuts and seeds may be beneficial in preventing these diseases. Dipteryx alata Vogel (DA), known popularly as Baru, belongs to the family Fabaceae and is a native fruit tree from the Brazilian savanna. The purpose of this study was to evaluate the use of seeds of DA on the metabolic and oxidative profile of Wistar rats. Animals were divided randomly into four groups (n = 10): G1 (control group), and G2 (treated with DA 20%), G3 (treated with DA 30%), and G4 (treated with DA 40%). After 40 days, animals were euthanized and metabolic and oxidative profiles were analyzed (glycemia, cholesterol, triglycerides [TGs], high-density lipoprotein-cholesterol [HDL-c], very low-density lipoprotein-cholesterol [VLDL-c], low-density lipoprotein-cholesterol [LDL-c], C reactive protein, aspartate aminotransferase, alanine aminotransferase, Lee index, weight, visceral fat, ferric reducing ability of plasma, and ferric-xylenol orange method. The use of the seeds was effective in reducing TGs, VLDL-c, LDL-c, and increasing HDL-c but did not interfere in the percentage of weight gain, visceral fat, levels of total cholesterol, and oxidative stress. Based on our results, it is possible to say that the use of DA may improve the lipid profile of Wistar rats and we may suggest that the consumption of DA almonds or products prepared with them may be an effective option for the intake of healthy products.

Potential radioprotective effect of AT1 receptor antagonists against morphological and ultrastructural changes in the testes induced by ionizing radiation / Potencial efecto radioprotector de antagonistas del receptor AT1 contra los daños morfológicos y ultraestructurales en los testículos inducido por la radiación ionizante

Radiotherapy is a source of human exposure to ionizing radiation. This pure energy causes deleterious effects on tissues, which result from oxidative stress, a phenomenon in which there is the participation of the Renin-Angiotensin System (RAS). The male genital organs are extremely radiosensitive and the action of radiation in the testes can significantly affect spermatogenesis. In search of potential radioprotective for male genital system, this study investigated whether the AT1 receptor antagonists minimize radiation-induced damage to reproductive tissues, by decreasing oxidative stress. Male Wistar rats were divided into six groups: 0 Gray (Gy) (control), 5 Gy (single dose in the scrotal area), telmisartan, losartan, 5Gy+telmisartan and 5Gy+losartan. The treatment started the day after irradiation with losartan 34 mg/kg (two times/day) and telmisartan 12 mg/kg (one time/day) during 60 days. For ultrastructural analysis, the testis fragments were fixed in 2 % glutaraldehyde and 4 % paraformaldehyde in 0.1 M phosphate buffer, pH 7.3. The material was postfixed for 2 h in 1 % osmium tetroxide. For collagen evaluation, the sections were stained with Picrosirius-red method. Serum testosterone was determined. The date showed the deleterious effects of gamma radiation on testicular ultrastructure. Rich accumulation of collagen fibers in the interstitium was observed in the irradiated groups, especially the irradiated and nontreated testes. No significant difference was detected in serum testosterone concentration among the studied experimental groups. Treatments with telmisartan and losartan influenced the onset of attenuation on ultrastructural damages arising from ionizing radiation. Although the data strongly suggest that AT1 receptor antagonists may promote radioprotection to the testes, further studies with a longer duration of treatment are required for these potentially positive effects to be maximized and, therefore, to better characterize radioprotection to reproductive parameters.

El tratamiento radioterápico es una fuente de exposición del ser humano a la radiación ionizante. Esta energía pura causa efectos deletéreos en los tejidos, debido al estrés oxidativo, fenómeno donde hay participación del Sistema Renina-Angiotensina. Los órganos genitales masculinos son extremadamente radiosensibles y la acción de la radiación en los testículos puede afectar significativamente la espermatogénesis. En la búsqueda de potenciales radioprotectores, este estudio ha investigado fármacos antagonistas del receptor AT1 que minimizan los daños radioinduzidos en los tejidos reproductivos, por medio de la disminución del estrés oxidativo. Ratones Wistar machos fueron distribuidos en seis grupos: grupo 0 Gray (Gy) (control), grupo 5 Gy (dosis única en el área escrotal), grupo telmisartán, grupo losartán, grupo 5Gy+telmisartán y grupo 5Gy+losartán. El tratamiento empezó en el día siguiente a la irradiación con losartán 34 mg/kg (2x/día) y telmisartán 12 mg/kg (1x/día), durante 60 días. Para el análisis ultraestructural, los testículos se fijaron en glutaraldehido (2 %) y paraformaldehido (4 %) con tampón de fosfato 0,1 M, pH 7,3. El material fue post-fijado en tetróxido de osmio (1 %). Para evaluar el colágeno fue utilizado el método Picrosirius Red. Fue determinada la concentración sérica de testosterona. Los datos mostraron los efectos deletéreos de los rayos gamma sobre la ultraestructura testicular. Fue observada una rica deposición de colágeno en el intersticio en los grupos irradiados, especialmente en el irradiado y no tratado. Entre los grupos, no se detectó ninguna diferencia significativa en la concentración sérica de testosterona. Los tratamientos con telmisartán y losartán influenciaron el comienzo de la atenuación de los cambios en la ultraestructura testicular de la radiación. A pesar de que los datos sugieren que los antagonistas del receptor AT1 pueden promover radioprotección a los testículos, estudios complementarios con una duración de tratamiento más extendida son necesarios para que los efectos potencialmente positivos sean maximizados y, por supuesto, puedan mejorar la caracterizacion de la radioprotección a los parámetros reproductivos.