RESUMO
Current and thorough information on the ecotoxicological consequences of pharmaceuticals is accessible globally. However, there remains a substantial gap in knowledge concerning the potentially toxic effects of COVID-19 used drugs, individually and combined, on aquatic organisms. Given the factors above, our investigation assumes pivotal importance in elucidating whether or not paracetamol, dexamethasone, metformin, and their tertiary mixtures might prompt histological impairment, oxidative stress, and apoptosis in the liver of zebrafish. The findings indicated that all treatments, except paracetamol, augmented the antioxidant activity of superoxide dismutase (SOD) and catalase (CAD), along with elevating the levels of oxidative biomarkers such as lipid peroxidation (LPX), hydroperoxides (HPC), and protein carbonyl content (PCC). Paracetamol prompted a reduction in the activities SOD and CAT and exhibited the most pronounced toxic response when compared to the other treatments. The gene expression patterns paralleled those of oxidative stress, with all treatments demonstrating overexpression of bax, bcl2, and p53. The above suggested a probable apoptotic response in the liver of the fish. Nevertheless, our histological examinations revealed that none of the treatments induced an apoptotic or inflammatory response in the hepatocytes. Instead, the observed tissue alterations encompassed leukocyte infiltration, sinusoidal dilatation, pyknosis, fatty degeneration, diffuse congestion, and vacuolization. In summary, the hepatic toxicity elicited by COVID-19 drugs in zebrafish was less pronounced than anticipated. This attenuation could be attributed to metformin's antioxidant and hormetic effects.
Assuntos
Acetaminofen , Fígado , Metformina , Estresse Oxidativo , Peixe-Zebra , Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Acetaminofen/toxicidade , Metformina/farmacologia , Dexametasona/farmacologia , COVID-19 , Apoptose/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Superóxido Dismutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Catalase/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
AIMS: The carotid bodies are sensors that detect physiological signals and convey them to the central nervous system, where the stimuli are processed inducing reflexes through efferent pathways. Recent studies have demonstrated that electrical stimulation of the carotid sinus nerve (CSN) triggers the anti-inflammatory reflex under different conditions. However, whether this electrical stimulation attenuates colitis was never examined. This study aimed to evaluate if the electrical CSN stimulation attenuates the experimental colitis induced by intrarectal administration of acetic acid in rats. METHODS: Electrodes were implanted around the CSN to stimulate the CSN, and a catheter was inserted into the left femoral artery to record the arterial pressure. The observation of hypotensive responses confirmed the effectiveness of the electrical CNS stimulation. This maneuver was followed by a 4 % acetic acid or saline administered intrarectally. After 24 h, colons were segmented into distal and proximal parts for macroscopy, histological and biochemical assessment. KEY FINDINGS: As expected, the electrical CSN stimulation was effective in decreasing arterial pressure in saline and colitis rats. Moreover, electrical CSN stimulation effectively reduced colonic tissue lesions, colitis scores, and histopathologic parameters associated with colitis. In addition, the CSN stimulation also reduced the colonic mucosa pro-inflammatory cytokine interleukin-1 beta, and increased the anti-inflammatory interleukin-10, in rats submitted to colitis. SIGNIFICANCE: These findings indicated that electrical CSN stimulation breaks the vicious cycle of local colon inflammation in colitis, which might contribute to its better outcome.
Assuntos
Seio Carotídeo , Colite , Ratos , Animais , Seio Carotídeo/fisiologia , Ácido Acético , Colite/induzido quimicamente , Colite/terapia , Reflexo , Estimulação Elétrica , Anti-InflamatóriosRESUMO
Inhalants are chemical substances that induce intoxication, and toluene is the main component of them. Increasing evidence indicates that a dependence on inhalants involves a state of chronic stress associated to the activation of immune cells in the central nervous system and release of proinflammatory mediators, especially in some brain areas such as the nucleus accumbens and frontal cortex, where the circuits of pleasure and reward are. In this study, anti-neuroinflammatory treatment based on a single dose of intranasal methylprednisolone was assessed in a murine model of chronic toluene exposure. The levels of proinflammatory mediators, expression levels of Iba-1 and GFAP, and histological changes in the frontal cortex and nucleus accumbens were evaluated after the treatment. The chronic exposure to toluene significantly increased the levels of TNF-α, IL-6, and NO, the expression of GFAP, and induced histological alterations in mouse brains. The treatment with intranasally administered MP significantly reduced the expression of TNF-α and NO and the expression of GFAP (p < 0.05); additionally, it reversed the central histological damage. These results indicate that intranasally administered methylprednisolone could be considered as a treatment to reverse neuroinflammation and histological damages associated with the use of inhalants.
RESUMO
SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.
RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.
Assuntos
Animais , Feminino , Ratos , Carnitina/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Antioxidantes/administração & dosagem , Carnitina/farmacologia , Ratos Wistar , Modelos Animais de Doenças , Intestinos/patologia , Antioxidantes/farmacologiaRESUMO
The Fundão Dam collapsed, on November 5th, 2015, dumping more than 50 million/m3 of iron ore tailings, enriched with metals, into the Doce River channel. The objective of this study was to evaluate the reproductive biology and histological damage in Astyanax lacustris specimens exposed to the metals from the dam collapse. The study was carried out at Doce River, in Espírito Santo State, Brazil. Monthly samplings were carried out for a year. Astyanax lacustris had multiple spawning: females' reproductive peak was in September, October, November, and December; and males between September, October, January, and February. There was a latency in the formation of gonads. For male gonads, it was necessary a 6 cm growth for it to increase from 30 to 50% and 4 cm for female gonads to increase from 40 to 50%. There is a positive correlation between gonad's concentration of Al and Fe and the rate of histological damage in females. Male gonads had a high rate of immature cells invading the cell lumen (47.36%) and female gonads showed a higher frequency of atresia (39.64%). Fish exposed to the contaminated water showed moderate-high gonad histological damage. The observed changes can directly influence the organism's development and reproduction in the long run, thus affecting A. lacustris population present in the region.
Assuntos
Caraciformes , Poluentes Químicos da Água , Animais , Brasil , Monitoramento Ambiental , Feminino , Masculino , Reprodução , Rios , Poluentes Químicos da Água/análiseRESUMO
The occurrence of persistent organic pollutants (POPs) in the environment can affect organisms inhabiting aquatic systems, in particular shallow lakes that are vulnerable to environmental stressors. This study aimed to assess POPs accumulation and changes at histological and physiological levels in tissues of three fish species with different trophic habits. Gills, brain, muscle, liver and gonads of Odontesthes bonariensis, Oligosarcus jenynsii and Cyphocharax voga were collected from the shallow lake La Peregrina, located in an agricultural area from Argentina. In addition, contaminant levels in surface water (SW), suspended particulate matter (SPM) and bottom sediments (BS) were assessed. Histological lesions were evaluated in fish tissues and levels of vitellogenin (VTG) were assessed in plasma of male fish in order to correlate these alterations with the presence of POPs in the environment. Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were determined by GC-ECD. Biotic and abiotic samples showed the same POPs distribution pattern: OCPs>PCBs>PBDEs. Although tissue distribution of OCPs was species-specific, muscle showed the lowest levels in all species. The most abundant contaminants were endosulfans, suggesting their widespread use in the area. O. bonariensis showed the highest endosulfans levels in liver (184.2-219ngg(-1)wet w), which was associated with the high SPM levels considering this species is a filter feeder. The occurrence of PCBs and PBDEs shows the ubiquity of these pollutants in the area. Histological lesions in gills and liver of O. bonariensis and O. jenynsii, might be related with the high levels of endosulfans in these organs. The detection of VTG in males warns about a possible exposure to estrogenic compounds in the environment. In conclusion, the simultaneous exposure of fish to multiple environmental pollutants leads to different alterations, so measures should be taken in order to prevent their occurrence and toxic effects.
Assuntos
Monitoramento Ambiental , Peixes/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Argentina , Ecossistema , Éteres Difenil Halogenados/metabolismo , Lagos/química , Masculino , Praguicidas/metabolismo , Bifenilos Policlorados/metabolismoRESUMO
The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.
Assuntos
Alumínio/toxicidade , Poluentes Ambientais/toxicidade , Intoxicação por Metais Pesados , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Intoxicação/fisiopatologia , Testículo/metabolismo , Testosterona/metabolismo , Alumínio/administração & dosagem , Animais , Resistência a Medicamentos , Poluentes Ambientais/administração & dosagem , Glutationa/metabolismo , Terapia de Reposição Hormonal/efeitos adversos , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metais Pesados/sangue , Metais Pesados/metabolismo , Orquiectomia/efeitos adversos , Oxirredução , Oxirredutases/metabolismo , Intoxicação/sangue , Intoxicação/metabolismo , Intoxicação/patologia , Distribuição Aleatória , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/uso terapêuticoRESUMO
In recent years, disorders related to the development and function of the male reproductive tract has increased, thus generating a surprising decrease in semen volume and sperm count. We examined the effects of low protein and estrogen on sexual behavior and testicular maturation in male rats. We also examined FSH, LH and testosterone levels and histological damage of testis tissue. The male rats were subjected to standard long-term treatment with estradiol by oral and paranteral delivery. The number of mounts, copulatory efficiency and ejaculation latencies for the paranteral protein diet (PPD) group was significantly lower than those in a group nourished with a low protein diet (LPD) and oral protein diet (OPD) groups (P<0.05). Testes and epididymis sections were examined by four grades, according to the level of damage of epithelium in the testes and epididymis. Higher histological damage was also detected in the PPD group. In conclusion, the present study confirmed that unwanted estrogen effects were higher in the paranteral administered group on examination of sexual behavior and histological damage of epithelium in the testes and epididymis of male rats.
En los últimos años, los trastornos relacionados con el desarrollo y la función del tracto reproductivo masculino han aumentado, lo que genera una disminución importante en el volumen de semen y el conteo de espermatozoides. Se examinaron los efectos de niveles bajos en proteínas y estrógeno en el comportamiento sexual y la maduración testicular en ratas macho. También se examinaron FSH, LH y los niveles de testosterona y el daño histológico de tejido testicular. Las ratas macho fueron sometidas al tratamiento y administración estándar a largo plazo con estradiol por vias oral y parenteral. El número de montajes, eficiencia de copulación y latencias de eyaculación para el grupo de dieta de proteínas parenteral (DPP) fue significativamente menor que los del grupo con una dieta baja en proteínas (PBD) y de proteína oral baja (POB) grupos (P<0,05). Fueron examinados los testículos y epidídimo de acuerdo a cuatro grados, en relación al nivel de daño del epitelio en los testículos y epidídimo. También se detectó un mayor daño histológico en el grupo DPP. En conclusión, se confirma que los efectos no deseados del estrógeno fueron mayores en el grupo con administración parenteral en el examen de conducta sexual y en el daño histológico del epitelio en los testículos y el epidídimo de ratas macho.
Assuntos
Animais , Masculino , Feminino , Ratos , Dieta com Restrição de Proteínas , Estradiol/administração & dosagem , Comportamento Sexual Animal/efeitos dos fármacos , Testículo/efeitos dos fármacos , Epididimo/patologia , Proteínas/administração & dosagem , Ratos Wistar , Maturidade Sexual , Testículo/patologiaRESUMO
Testis-mediated gene transfer (TMGT) has been used as in vivo gene transfer technology to introduce foreign DNA directly into testes, allowing mass gene transfer to offspring via mating. In this study, we used plasmid DNA (pEGFP-N1) mixed with dimethylsulfoxide (DMSO), N,N-dimethylacetamide (DMA) or liposome (Lipofectin) in an attempt to improve TMGT. Males receiving consecutive DNA complex injections were mated to normal females to obtain F0 progeny. In vivo evaluation of EGFP expression, RT-PCR and PCR were used to detect the expression and the presence of exogenous DNA in the progeny. We also evaluated possible testicular damage by histological procedures. PC R and RT-PCR analyses revealed that liposome and DMSO increased the rate of TMGT. Histological analyses demonstrated that repeated (4 times) injections of DNA complexes can affect spermatogenesis. DMSO was the most deleterious among the reagents tested. In this study, we detected the presence of transgene in the progeny, and its expression in blood cells. Consecutive injections of DNA complexes were associated with impaired spermatogenesis, suggesting requirement of optimal conditions for DNA delivery through TMGT.