RESUMEN
In this work, we investigated the effects of red orange and lemon extract (RLE) on ochratoxin A (OTA)-induced nephrotoxicity. In particular, we analyzed the change in renal function and oxidative stress in Sprague-Dawley rats treated with OTA (0.5 mg/kg body weight, b.w.) and with RLE (90 mg/kg b.w.) by oral administration. After OTA treatment, we found alterations of biochemical and oxidative stress parameters in the kidney, related to a severe decrease of glomerular filtration rate. The RLE treatment normalized the activity of antioxidant enzymes and prevented the glomerular hyperfiltration. Histopathological examinations revealed glomerular damages and kidney cortex fibrosis in OTA-rats, while we observed less severe fibrosis in OTA plus RLE group. Then, we demonstrated that oxidative stress could be the cause of OTA renal injury and that RLE reduces this effect.
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Citrus sinensis/química , Citrus/química , Enfermedades Renales/tratamiento farmacológico , Insuficiencia Renal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Tasa de Filtración Glomerular , Humanos , Riñón/diagnóstico por imagen , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Ocratoxinas/toxicidad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/patologíaRESUMEN
Cryptorchidism is associated with changes in the gonads and the spermatic duct system, which may cause infertility problems. Urocortin (UCN) is a corticotrophin-releasing hormone (CRH)-related peptide, which affects several functions of male genital organs. The aim of the present study was to investigate the expression of UCN and its receptors CRHR1 and CRHR2 using immunohistochemistry, western blotting and real-time reverse transcription polymerase chain reaction in tissues collected from the epididymis of normal and cryptorchid dogs. The lumen of the cryptic epididymal duct was found to be relatively smaller than that of the normal one, and interstitial tissue was abundant in the cryptic epididymis. In addition, only a few spermatids were observed in the lumen of the epididymal duct. Results showed that UCN, CRHR2 and CRHR1 were expressed in tissues collected from normal and cryptic epididymal ducts. Urocortin- and CRHR2-immunoreactivities (IRs) were detected in the principal cells of the caput, corpus and cauda of the normal and cryptic epididymides. CRHR1-IR was detected in vascular smooth muscles and fibromuscular cells surrounding epididymal tubules of the normal and cryptorchid dogs. Expression levels of UCN and CRHR2 mRNA were higher in cryptic epididymal ducts than that in normal epididymal ducts. These results suggest that UCN and its receptors might play a role in regulating the maturation and storage of spermatozoa. These findings indicated that the expression of these proteins could be modulated by the cryptorchidism condition.
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Criptorquidismo/veterinaria , Enfermedades de los Perros/patología , Perros , Epidídimo/metabolismo , Urocortinas/metabolismo , Animales , Epidídimo/anomalías , Masculino , ARN Mensajero , Receptores de Hormona Liberadora de Corticotropina/genética , Espermátides , Distribución Tisular , Urocortinas/genéticaRESUMEN
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that represent toxic real threat for human beings and animal health. In this study we evaluated the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) on oxidative stress and on the alterations of fluid reabsorption in renal proximal tubule (PT) as possible causes of OTA nephrotoxicity. Finally, we have measured the concentration of O2- in the kidney through dihydroethidium assay (DHE) and nitric oxide (NO) concentration through nitrites and nitrates assay. Male Sprague Dawley rats weighing 120-150 g were treated for 14 days by gavage, as follows: Control group, 12 rats received a corresponding amount of saline solution (including 10% DMSO); rMnSOD group, 12 rats treated with rMnSOD (10 µg/kg bw); OTA group, 12 rats treated with OTA (0.5 mg/kg bw) dissolved in 10% DMSO and then scaled to required volume with corn oil; rMnSOD + OTA, 12 rats treated with rMnSOD (10 µg/kg bw) plus OTA (0.5 mg/kg bw). Our results have shown that rMnSOD restores the alteration of reabsorption in PT in rats treated with OTA plus rMnSOD, probably through the response to pressure natriuresis, where nitric oxide plays a key role. Moreover, rMnSOD prevents the nephrotoxicity induced by OTA probably restoring the balance between superoxide and NO that is most probably the cause of hypertension and renal functional alterations through the inhibition of NO synthase. In conclusion these data provide important information for understanding of mechanism of toxic action of OTA. J. Cell. Biochem. 119: 424-430, 2018. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Túbulos Renales Proximales/metabolismo , Ocratoxinas/toxicidad , Reabsorción Renal/efectos de los fármacos , Superóxido Dismutasa/farmacología , Animales , Humanos , Túbulos Renales Proximales/patología , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacologíaRESUMEN
BACKGROUND: Cryptorchidism is one of the most common birth disorders of the male reproductive system identified in dogs and other mammals. This condition is characterised by the absence of one (unilateral) or both (bilateral) gonads from the scrotum. The peptides orexin A (OxA) and B (OxB) were obtained by post-transcriptional proteolytic cleavage of a precursor molecule, called prepro-orexin. These substances bind two types of G-coupled receptors called receptor 1 (OX1R) and 2 (OX2R) for orexins. OX1R is specific to OxA while OX2R binds the two peptides with equal affinity. Orexins modulate a great variety of body functions, such as the reproductive mechanism. The purpose of the present research was to study the presence of OxA and its receptor 1 and their possible involvement in the canine testis under healthy and pathological conditions. METHODS: This study was performed using adult male normal dogs and male dogs affected by unilateral cryptorchidism. Tissue samples were collected from testes and were divided into three groups: normal, contralateral and cryptic. The samples were used for immunohistochemistry, Western blot and in vitro tests for testosterone evaluation in normal and pathological conditions. RESULTS: OxA-immunoreactivity (IR) was described in interstitial Leydig cells of the normal gonad, and Leydig, Sertoli cells and gonocytes in the cryptic gonad. In the normal testis, OX1R-IR was described in Leydig cells, in pachytene and second spermatocytes and in immature and mature spermatids throughout the stages of the germ developing cycle of the male gonad. In the cryptic testis OX1R-IR was distributed in Leydig and Sertoli cells. The presence of prepro-orexin and OX1R was demonstrated by Western blot analysis. The incubation of fresh testis slices with OxA caused the stimulation of testosterone synthesis in the normal and cryptic gonad while the steroidogenic OxA-induced effect was cancelled by adding the selective OX1R antagonist SB-408124. CONCLUSIONS: These results led us to hypothesise that OxA binding OX1R might be involved in the modulation of spermatogenesis and steroidogenesis in canine testis in healthy and pathological conditions.
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Criptorquidismo/veterinaria , Enfermedades de los Perros/metabolismo , Receptores de Orexina/metabolismo , Orexinas/metabolismo , Animales , Western Blotting/veterinaria , Criptorquidismo/metabolismo , Criptorquidismo/patología , Enfermedades de los Perros/patología , Perros , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/patología , Masculino , Células de Sertoli/metabolismo , Células de Sertoli/patología , Testosterona/metabolismoRESUMEN
Ochratoxin A (OTA) is a natural mycotoxin, involved in the development of important human and animal diseases. In this work we have studied the role of oxidative stress in the development of OTA nephrotoxicity and the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) to prevent kidney damage induced by OTA. Blood pressure, glomerular filtration rate and renal histology were analyzed in control rats and in OTA treated rats. In addition, lipid peroxidation, catalase and superoxide dismutase productions were measured. Our data showed that animals treated with OTA presented hypertension and reduction of glomerular filtration rate (GFR). These effects are most probably related to an increase in the reactive oxygen species (ROS) productions. In fact, we have shown that treatment with rMnSOD restored the levels of blood pressure and GFR simultaneously. Moreover, we have noted that OTA induced alteration on glomerular and tubular degeneration and interstitial infiltrates and that use of rMnSOD combined with OTA prevent this renal histological damage confirming the potential therapeutic role in the treatment of rMnSOD OTA nephrotoxicity.
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Enfermedades Renales/prevención & control , Manganeso/química , Ocratoxinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Proteínas Recombinantes/administración & dosificación , Superóxido Dismutasa/química , Animales , Presión Sanguínea/efectos de los fármacos , Tasa de Filtración Glomerular/efectos de los fármacos , Enfermedades Renales/inducido químicamente , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/farmacología , Superóxido Dismutasa/administración & dosificación , Superóxido Dismutasa/farmacologíaRESUMEN
Aquaporins (AQPs) play a pivotal role in gut homeostasis since their distribution and function is modulated both in physiological and in pathophysiological conditions. The transport of water and solutes through gut epithelia is essential for osmoregulation and digestive and absorptive functions. This passage is regulated by different AQP isoforms and characterized by their peculiar distribution in the gastrointestinal tract. To date, AQP localization has been identified in the gut and associated organs of several mammalian species by different techniques (immunohistochemical, western blotting, and RT-PCR). The present review describes the modulation of AQP expression, distribution, and function in gut pathophysiology. At the same time, the comparative description of AQP in animal species sheds light on the full range of AQP functions and the screening of their activity as transport modulators, diagnostic biomarkers, and drug targets. Moreover, the phenotype of knockout mice for several AQPs and their compensatory role and the use of specific AQP inhibitors have been also reviewed. The reported data could be useful to design future research in both basic and clinical fields.
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Acuaporinas/metabolismo , Enfermedades Gastrointestinales/fisiopatología , Tracto Gastrointestinal/fisiología , Animales , Transporte Biológico , Humanos , RatonesRESUMEN
Cyclosporine A (CsA) is the prototype of immunosuppressant drugs that has provided new perspectives in human and veterinary medicine to prevent organ transplant rejection and to treat certain autoimmune diseases and dermatologic diseases. Unfortunately, the treatment with CSA is often limited by severe adverse effects such as hypertension and nephrotoxicity. Some data suggest that reactive oxygen species (ROS) and the oxidative stress play an important role in its pathogenesis, in particular the superoxide (O2 (-)) that is the most powerful free radical generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase present mainly in the kidney. The present study has been designed to investigate the role of Apocynin a selective inhibitor of NADPH oxidase activity on cyclosporine-induced adverse effect. In this study, we have evaluated the effect of CsA, used alone or in association with Apocynin on blood pressure (BP), on glomerular filtration rate (GFR), on absoluted fluid reabsorption (Jv) in proximal tubule (PT), on O2 (-) concentration, and on nitric oxide (NO) production. We have demonstrated that CsA administration increases superoxide concentration in the aorta, decreases the NO concentration, reduces GFR and the Jv in PT, and induces a significant increase in BP. Moreover, we have shown that Apocynin treatment restores these hemodynamic alterations, as well as NO and superoxide productions. In conclusion, the reported data indicate that CsA induced nephrotoxicity and hypertension are related to NADPH oxidase activity, in fact Apocynin protects the kidney function and BP from toxic effects induced by CsA through the inhibition of NADPH oxidase activity.
Asunto(s)
Acetofenonas/administración & dosificación , Ciclosporina/efectos adversos , Inhibidores Enzimáticos/administración & dosificación , Hipertensión/prevención & control , Enfermedades Renales/prevención & control , Acetofenonas/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Hipertensión/etiología , Enfermedades Renales/etiología , Masculino , NADPH Oxidasas/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Orexins A (OXA) and B (OXB) and their specific receptors, receptor 1 (OX1R) and 2 (OX2R) for orexins, are hypothalamic peptides involved in orchestrating several functions in the central nervous system and peripheral organs, including sleep, excitement, nutrition, reward, circadian rhythm, anxiety, cognition, and reproduction. The aim of this narrative review is, in particular, to speculate the role of orexins in the male genital tract of animal species and human beings. The experimental evidence collected in recent years assumed that in the testes of the animal species here described, orexins are directly involved in steroidogenesis and spermatogenesis regulation. In the epididymis, these peptides are locally synthesized, thus suggesting their role governing the fertilizing capability of the immature male gamete. In addition to playing a physiological role, orexins are involved in numerous inflammatory and/or neoplastic pathologies too. The expression of the orexinergic system in prostate cancer suggests that they might play a potential therapeutic function. Overall, the future directions of this literature review allow us to hypothesize a role of the orexinergic complex not only as a marker for the diagnosis of certain tumors affecting the male genital tract but also for the treatment of hypo/infertility condition.
RESUMEN
There is growing evidence by the literature that the unbalance between androgens and estrogens is a relevant condition associated with a common canine reproductive disorder known as cryptorchidism. The role of estrogens in regulating testicular cell function and reproductive events is supposedly due to the wide expression of two nuclear estrogen receptors (ERs), ER-alpha and ER-beta and a trans-membrane G protein-coupled estrogen receptor (GPER) in the testis. In this study, immunohistochemistry, Western blotting and qRT-PCR were used to assess the distribution and expression of GPER in the testis-epididymal complex in the normal and cryptorchid dog. ER-alpha and ER-beta were also evaluated to better characterize the relative abundances of all three receptors. In addition, in these tissues, the expression level of two proteins as SOD1 and Nrf2 normally associated with oxidative stress was investigated to evaluate a possible relationship with ERs. Our data revealed changes in the distribution and expression of the GPER between the normal and cryptorchid dog. In particular, dogs affected by cryptorchidism showed an upregulation of GPER at level of the examined reproductive tract. Also considering the obtained result of a modulation of SOD1 and Nrf2 expression, we could hypothesize the involvement of GPER in the cryptorchid condition. Further studies are, however, necessary to characterize the role of GPER and its specific signaling mechanisms.
RESUMEN
Urocortin (UCN) is a 40-amino-acid peptide and a member of the corticotropin-releasing hormone (CRH) family, which includes CRH, urotensin I, sauvagine, UCN2 and UCN3. The biological actions of CRH family peptides are mediated via two types of G-protein-coupled receptors, namely CRH type 1 receptor (CRHR1) and CRH type 2 receptor (CRHR2). The biological effects of these peptides are mediated and modulated not only by CRH receptors but also via a highly conserved CRH-binding protein (CRHBP). Our aim was to investigate the expression of UCN, CRHR1, CRHR2 and CRHBP by immunohistochemistry, Western blot and reverse transcription with the polymerase chain reaction (RT-PCR) in the horse thyroid gland. The results showed that UCN, CRHR1 and CRHR2 were expressed in the thyroid gland, whereas CRHBP was not expressed. Specifically, UCN immunoreactivity (-IR) was found in the thyroid follicular cells, CRHR2-IR in the C-cells and CRHR1-IR in blood vessels. Western blot analysis and RT-PCR experiments confirmed the immunohistochemical data. These results suggest that a regulatory system exists in the mammalian thyroid gland based on UCN, CRHR1 and CRHR2 and that UCN plays a role in the regulation of thyroid physiological functions through a paracrine mechanism.
Asunto(s)
Proteínas Portadoras/metabolismo , Caballos/metabolismo , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Glándula Tiroides/metabolismo , Urocortinas/metabolismo , Animales , Western Blotting , Proteínas Portadoras/genética , Femenino , Regulación de la Expresión Génica , Inmunohistoquímica , Inmunoprecipitación , Masculino , Receptores de Hormona Liberadora de Corticotropina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Glándula Tiroides/citología , Urocortinas/genéticaRESUMEN
The orexins A (oxA) and B are peptides discovered in the rat hypothalamus and successively found in some peripheral organs of the mammalian body. They binds two protein G-coupled receptors defined receptor 1 (ox1r) and 2 for orexins, the first of which is highly specific for oxA while the second binds both the peptides with equal affinity. This work aimed to detect the presence of oxA and ox1r in the testis of the South American camelid alpaca (Vicugna pacos) and investigate the role played by them on Leydig cell steroidogenesis. The species alpaca acquired, in the last years, increasing zootechnical interest for the quality of the wool produced and its breeding spread from the country of origin to USA, Australia and Europe. Immunohistochemistry allowed us to detect oxA in Leydig and Sertoli cells, spermatogonia, resting spermatocytes, round and oval spermatids. Ox1r-immunoreactivity was found in Leydig cells and round, oval and elongated spermatids. The expression of the two peptides in tissue extracts was established by using Western blotting technique. Such results demonstrated that in the alpaca testis exists in a cellular complex able to produce and/or internalize oxA. Finally, the effect of oxA on steroidogenesis was investigated by means of in vitro cultured thin testis slices which were added with oxA or/and Müllerian Inhibiting Substance (MIS), a steroidolitic agent basally produced by the Sertoli cell. OxA evoked increase of testosterone production while MIS a decrease. The consecutive addition of oxA and MIS, or vice versa, highlighted an antagonistic interplay between the two substances which has been thought to be the main molecular event at the basis of the oxA-stimulated steroidogenesis mechanism.
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Camélidos del Nuevo Mundo/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neuropéptidos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Testículo/metabolismo , Animales , Hormona Antimülleriana/farmacología , Péptidos y Proteínas de Señalización Intracelular/farmacología , Péptidos y Proteínas de Señalización Intracelular/fisiología , Células Intersticiales del Testículo/metabolismo , Masculino , Neuropéptidos/farmacología , Neuropéptidos/fisiología , Receptores de Orexina , Orexinas , Receptores Acoplados a Proteínas G/fisiología , Receptores de Neuropéptido/fisiología , Testículo/efectos de los fármacos , Testosterona/biosíntesis , Testosterona/metabolismoRESUMEN
Orexins A (OXA) and B (OXB) and the receptors 1 (OX1R) and 2 (OX2R) for orexins are hypothalamic peptides found in several mammalian organs and participated to the control of a wide assortment of physiological and pathological functions. The distribution of OXA and OX1R has been extensively studied in the male gonad of mammals. Here, we examined the expression and localization of OXB and OX2R as well as their possible involvement in the regulation of testicular and epididymal functions, in healthy and cryptorchid dogs, employing some techniques such as immunohistochemistry, Western blotting, and real-time RT-PCR. In vitro tests were also carried out for evaluating the steroidogenic effect of OXB. OXB and OX2R were expressed in spermatocytes, spermatids, and Leydig cells in normal testis. Their localization was restricted to Sertoli and Leydig cells in cryptorchid conditions. OXB was found to be localized in all tracts of both normal and cryptorchid epididymis, whereas OX2R was found only in the caput. Because the small molecular weight of the peptides OXA and OXB, the expression of their precursor prepro-orexin (PPO), OX1R, and OX2R proteins and mRNAs were investigated by means of Western blot and real-time RT-PCR analyses, respectively, in all tested groups of. In particular, the mRNA level expression of all three genes was higher in cryptorchid dogs than in normal ones. In vitro tests demonstrated that OXB-by binding OX2R-is not involved in testicular steroidogenic processes. Therefore, the findings of this study might be the basis for further functional and molecular studies addressing the possible biochemical effects of OXB and OX2R in normal and pathological conditions of the male reproductive system.
RESUMEN
Urocortin (UCN), a 40 amino acid peptide, is a corticotrophin-releasing hormone (CRH)-related peptide. The biological actions of CRH family peptides are mediated via two types of G protein-coupled receptors, CRH type 1 receptor (CRHR1) and CRH type 2 receptor (CRHR2). The aim of the present study was to investigate the expression of UCN, CRHR1 and CRHR2 by immunohistochemistry, western blot and real-time RT-PCR in the bovine adrenal gland to clarify the mechanisms of the intra-adrenal CRH-based regulatory system. The results showed that UCN, CRHR1 and CRHR2 were expressed in both the cortex and medulla. Specifically, UCN-immunoreactivity (IR) was distributed in the outer part of the zona fasciculata and in the zona reticularis of the cortex and in the medulla. UCN and CRHR2 mRNA expression levels were higher in the cortex than in the medulla, while CRHR1 mRNA levels were undetectable in the cortex. These results suggest that UCN, CRHR1 and CRHR2 are expressed in the bovine adrenal gland and that UCN might play a role in the intra-adrenal CRH-based regulatory system through an autocrine mechanism.
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Glándulas Suprarrenales/metabolismo , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Urocortinas/metabolismo , Animales , Western Blotting , Bovinos , Femenino , Inmunohistoquímica , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The efferent ductules and the epididymis are parts of the male reproductive system where spermatozoa mature. Specialized epithelial cells in these ducts contribute to the transport of fluids produced by spermatozoa's metabolic activity. Aquaporins (AQPs) have been demonstrated to be expressed in the spermatozoan membrane and testis epithelial cells, where they contribute to regulating spermatozoan volume and transit through environments of differing osmolality. Due to the lack of detailed literature regarding AQP expression in the canine male genital tract, the aim of this study was to investigate both the distribution and expression of AQP7, AQP8, and AQP9 in the efferent ductules and epididymal regions (caput, corpus, and cauda) from normal and cryptorchid dogs by using immunohistochemistry, Western blotting, and real-time reverse transcription polymerase chain reaction (RT-PCR). Our results show different patterns for the distribution and expression of the examined AQPs, with particular evidence of their upregulation in the caput and downregulation in the cauda region of the canine cryptorchid epididymis. These findings are associated with a modulation of Hsp70 and caspase-3 expression, suggesting the participation of AQPs in the luminal microenvironment modifications that are peculiar characteristics of this pathophysiological condition.
RESUMEN
Aquaporins (AQPs) are integral transmembrane proteins facilitating transport of water and small solutes, such as glycerol and urea, between cells. In male reproductive tracts, AQPs maintain a milieu conducive for sperm formation, maturation, and storage. The aim of this study was to clarify effects of testicular and epidydimal function on male fertility by investigating localisation and abundances of AQP3 and AQP5 in testes and epididymal segments from dogs with and without unilateral cryptorchidism. Immunohistochemistry results indicated AQP3 and AQP5 have different distribution patterns in reproductive tissues of dogs with and without unilateral cryptorchidism. The AQP3, an aquaglyceroprotein, is present in different germ and Sertoli cells in testis of dogs without cryptorchidism. The AQP5 protein was not detected in germ cells but was present in Sertoli and Leydig cells and in endothelia of blood vessels. In cryptorchid dogs, AQP3 was detected in early-developing germ and Sertoli cells, and AQP5 had a distribution pattern similar to testes of dogs without cryptorchidism. In the epididymis, AQP3 and AQP5 were localised in epithelial cells of dogs with and without cryptorchidism in a cell-specific manner. The AQP3 and AQP5 protein was in larger abundance in the gonads from dogs with and without cryptorchidism. In contrast, AQP3 and AQP5 abundance increased in each segment of the cryptorchid epididymis, likely as a compensatory mechanism associated with the pathologic condition. These results indicate involvement of AQP3 and AQP5 in spermatogenesis and sperm maturation. Results from the present study indicate dogs are a useful for comparative reproductive biology studies.
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Acuaporina 3/metabolismo , Acuaporina 5/metabolismo , Criptorquidismo/metabolismo , Enfermedades de los Perros/metabolismo , Epidídimo/metabolismo , Testículo/metabolismo , Animales , Acuaporina 3/genética , Acuaporina 5/genética , Estudios de Casos y Controles , Perros , Inmunohistoquímica/veterinaria , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Ochratoxin A (OTA) is a powerful mycotoxin found in various foods and feedstuff, responsible for subchronic and chronic toxicity, such as nephrotoxicity, hepatotoxicity, teratogenicity, and immunotoxicity to both humans and several animal species. The severity of the liver damage caused depends on both dose and duration of exposure. Several studies have suggested that oxidative stress might contribute to increasing the hepatotoxicity of OTA, and several antioxidants, including curcumin (CURC), have been tested to counteract the toxic hepatic action of OTA in various classes of animals. Therefore, the present study was designed to evaluate the protective effect of CURC, a bioactive compound with different therapeutic properties on hepatic injuries caused by OTA in rat animal models. CURC effects were examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. At the end of the experiment, rats treated with OTA showed alterations in biochemical parameters and oxidative stress in the liver. CURC dosing significantly attenuated oxidative stress and lipid peroxidation versus the OTA group. Furthermore, liver histological tests showed that CURC reduced the multifocal lymphoplasmacellular hepatitis, the periportal fibrosis, and the necrosis observed in the OTA group. This study provides evidence that CURC can preserve OTA-induced oxidative damage in the liver of rats.
RESUMEN
Ochratoxin A (OTA) is a powerful nephrotoxin and the severity of its damage to kidneys depends on both the dose and duration of exposure. According to the scientific data currently available, the mechanism of action still is not completely clarified, but it is supposed that oxidative stress is responsible for OTA-induced nephrotoxicity. Bioactive compound use has emerged as a potential approach to reduce chronic renal failure. Therefore, curcumin (CURC), due to its therapeutic effects, has been chosen for our study to reduce the toxic renal effects induced by OTA. CURC effects are examined in Sprague Dawley rats treated with CURC (100 mg/kg), alone or in combination with OTA (0.5 mg/kg), by gavage daily for 14 days. The end result of the experiment finds rats treated with OTA show alterations in biochemical and oxidative stress parameters in the kidney, related to a decrease in the Glomerular Filtration Rate (GFR). Conversely, the administration of CURC attenuates oxidative stress and prevents glomerular hyperfiltration versus the OTA group. Furthermore, kidney histological tests show a reduction in glomerular and tubular damage, inflammation and tubulointerstitial fibrosis. This study shows that CURC can mitigate OTA-induced oxidative damage in the kidneys of rats.
RESUMEN
Urocortins (Ucns), peptides belonging to the corticotropin-releasing hormone (CRH) family, are classified into Ucn1, Ucn2, and Ucn3. They are involved in regulating several body functions by binding to two G protein-coupled receptors: receptor type 1 (CRHR1) and type 2 (CRHR2). In this review, we provide a historical overview of research on Ucns and their receptors in the mammalian endocrine system. Although the literature on the topic is limited, we focused our attention particularly on the main role of Ucns and their receptors in regulating the hypothalamic-pituitary-adrenal and thyroid axes, reproductive organs, pancreas, gastrointestinal tract, and other tissues characterized by "diffuse" endocrine cells in mammals. The prominent function of these peptides in health conditions led us to also hypothesize an action of Ucn agonists/antagonists in stress and in various diseases with its critical consequences on behavior and physiology. The potential role of the urocortinergic system is an intriguing topic that deserves further in-depth investigations to develop novel strategies for preventing stress-related conditions and treating endocrine diseases.
Asunto(s)
Sistema Endocrino/fisiología , Urocortinas/metabolismo , Animales , Enfermedades del Sistema Endocrino/fisiopatología , Investigación/tendencias , Estrés Fisiológico , Urocortinas/agonistas , Urocortinas/antagonistas & inhibidoresRESUMEN
Orexin A (OxA) is a neuropeptide produced in the lateral hypothalamus that performs pleiotropic functions in different tissues, including involvement in energy homeostasis and reproductive neuroendocrine functions. The role of OxA is particularly important given the well-studied relationships between physiological mechanisms controlling energy balance and reproduction. The enzyme P450 aromatase (ARO) helps convert androgens to estrogens and has roles in steroidogenesis, spermatogenesis, and energy metabolism in several organs. The goal of this study was thus to investigate the role of OxA in ARO activity and the effects of this regulation on reproductive homeostasis in male gonads from healthy and cryptorchid dogs. The cryptorchidism is a specific condition characterized by altered reproductive and metabolic activities, the latter of which emerge from impaired glycolysis. OxA helps to stimulate testosterone (T) synthesis in the dog testis. We aimed to investigate OxA-mediated modulation of 17ß-estradiol (17ß-E) synthesis, ARO expression and metabolic indicators in testis of normal and cryptorchid dogs. Our results indicate putative effects of OxA on estrogen biosynthesis and ARO activity based on western blotting analysis and immunohistochemistry for ARO detection and in vitro tests. OxA triggered decrease in estrogen production and ARO activity inhibition; reduced ARO activity thus prevented the conversion of T to estrogens and increasing OxA-mediated synthesis of T. Furthermore, we characterized some metabolic and oxidative modulations in normal and cryptorchid dog's testis. The steroidogenic regulation by OxA and its modulation of ARO activity led us to hypothesize that OxA is a potential therapeutic target in pathological conditions associated with steroidogenic alterations and OxA possible involvement in metabolic processes in the male gonad.
RESUMEN
Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) and are members of the neurotrophin family, a family of neurotrophic factors that also includes neurotrophin (NT) 3 and NT4/5. Neurotrophins have essential roles in the survival, development and differentiation of neurons in the central and peripheral nervous systems. Neurotrophins exert their effects by binding to corresponding receptors which are formed by the tyrosine protein kinases TrkA, TrkB and TrkC, and the low affinity neurotrophic receptor (p75NTR). In the present study, using immunohistochemistry and quantitative analysis, we have investigated immunoreactivity to BDNF, NGF, TrkB, p75NTR and TrkA in the pelvic ganglia of normal and castrated rats. Neurons of the pelvic ganglia expressed both these neurotrophins and their receptors. After castration the immunoreactivity persisted. However, the number of BDNF- and p75NTR-IR cells statistically significant decreased after castration. These results suggest that castration modulates the expression of neurotrophins and their receptors in pelvic autonomic neurons.