A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.

Impacts of heavy metal exposure on the prostate of murine models: Mechanisms of toxicity.

Heavy metals are elements found into the environment mainly due to anthropogenic activities. Naturally occurring and higher released doses cause disorders in the prostate, which depends on appropriate hormonal regulation, and exposure to heavy metals may impair prostate homeostasis. The current work highlighted the main mechanisms of toxicity of different environmental heavy metal contaminants, such as aluminum, arsenic, cadmium, chromium, lead, mercury, and nickel, and their impacts found in the prostate morphophysiology of murine models. The repercussions triggered by heavy metals on the prostate include hormonal imbalance and oxidative damage, leading to morphological alterations, which can vary according to the chemical properties of each element, exposure time and concentration, and age. The information of altered biological pathways and its impacts on the prostate of exposed murines are related to human outcomes being useful in the real context of human exposure.

The Mongolian Gerbil as a Useful Experimental Model in Reproductive Biology.

Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.

Aluminum intake in the neonatal phase disrupts endochondral ossification in rodents.

OBJECTIVE: This study evaluated the effects of aluminum (Al) intake on endochondral ossification during the neonatal phase. METHOD: Twelve male newborn Gerbils (Meriones unguiculatus) were randomly divided into control (C) and aluminum (Al) groups (n = 6 animals/group). From the 1st to 15th day of life, gerbils received an AlCl3 solution (10 mg/kg/day) via gavage. The control group received only the saline solution. On the 16th day, their tibias were processed for paraffin embedding and were submitted to histomorphometric, histochemical, and immunohistochemical analyses. RESULTS: In the epiphyseal cartilage Al did not affect the proteoglycan content or cell proliferation; however, it increased matrix metalloprotease-2 (MMP-2) immunostaining and the hypertrophic layer thickness. In bone, Al decreased trabeculae number, trabecular width, cortical bone width, and proliferation. Furthermore, the relative frequency of bone matrix and fibrillar collagen decreased 3.9% and 16.2%, respectively. The number of osteoclasts and osteocalcin digital optical density (D.O.D) remained the same. CONCLUSION: The results suggest that Al intake during the neonatal period impairs endochondral ossification by affecting epiphyseal cartilage and bone architecture.

Subacute exposure to aluminum chloride causes prolonged morphological insults in the ventral male prostate and in the female prostate of adult gerbils.

Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl3 ) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl3 (10 mg/kg) for 30 consecutive days. The animals were euthanized 1 day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate.

Protective effects of chrysin against the neurotoxicity induced by aluminium: In vitro and in vivo studies.

Chronic exposure to aluminium (Al) can contribute to the progression of several neurological and neurodegenerative diseases. Al is a metal that promotes oxidative damage leading to neuronal death in different brain regions with behavior, cognition, and memory deficits. Chrysin is a flavonoid found mainly in honey, passion fruit, and propolis with antioxidant, anti-inflammatory, and cytoprotective properties. In this study, we used an integrated approach of in vitro and in vivo studies to evaluate the antioxidant and neuroprotective effects of chrysin against the neurotoxicity elicited by aluminium chloride (AlCl3). In in vitro studies, chrysin (5 µM) showed the ability to counteract the early oxidative stress elicited by tert-butyl hydroperoxide, an oxidant that mimics the lipid peroxidation and Fenton reaction in presence of AlCl3 as well as the late necrotic death triggered by AlCl3 in neuronal SH-SY5Y cells. In vivo studies in a mouse model of neurotoxicity induced by chronic exposure to AlCl3 (100 mg/kg/day) for ninety days then corroborated the antioxidant and neuroprotective effect of chrysin (10, 30, and 100 mg/kg/day) using the oral route. In particular, chrysin reduced the cognitive impairment induced by AlCl3 as well as normalized the acetylcholinesterase and butyrylcholinesterase activities in the hippocampus. In parallel, chrysin counteracted the oxidative damage, in terms of lipid peroxidation, protein carbonylation, catalase, and superoxide dismutase impairment, in the brain cortex and hippocampus. Lastly, necrotic cells frequency in the same brain regions was also decreased by chrysin. These results highlight the ability of chrysin to prevent the neurotoxic effects associated with chronic exposure to Al and suggest its potential use as a food supplement for brain health.

Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats.

The proline-rich oligopeptide from Bothrops jararaca snake venom, Bj-PRO-7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj-PRO-7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj-PRO-7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non-treated SHR at the end of the treatment. However, Bj-PRO-7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA-labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj-PRO-7a increased the expression of metalloproteinases-2 in SHR hearts. These findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodelling in a pressure-independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation.

Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate.

The aim of this study was to evaluate whether high levels of exogenous testosterone (T) interfere in prostate morphogenesis. Pregnant females were exposed to subcutaneous injections of T cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were euthanized at postnatal days 1 and 15. 15-day-old males had only fibroblast growth factor 10 (FGF10) immunostaining and nuclear form factor altered by the treatment, whereas treated females (T1 and T15) had almost all analyzed parameters changed. T1 females showed an increased anogenital distance (AGD), whereas T15 females had both AGD and ovary weight increased. T1 females had a higher number of epithelial buds emerging from the urethral and vaginal epithelium. We observed ectopic prostatic tissue surrounding the vagina in both T1 and T15 females. Moreover, the ectopic acini of T15 females showed delayed luminal formation, and there was a thickening of the periacinar smooth muscle layer (SML). Finally, FGF10 immunostaining intensity decreased in both T15 male and female prostates. Indeed, Sonic hedgehog (Shh) was upregulated in T15 female prostates, whereas no difference was observed between the male groups. These data showed that exogenous T changed the nuclear morphology of prostate epithelial cells in both males and females. Surprisingly, smooth muscle hyperplasia was also observed in the ectopic female prostate. Moreover, T downregulated FGF10 in both male and female prostates. Interestingly, the results suggest that FGF10 downregulation is mediated by the upregulation of Shh in females. In conclusion, exogenous T disrupts prostate development, particularly, affecting, the female.

The Influence of Pregnancy on Female Prostate Morphophysiology in Gerbils (Meriones unguiculatus).

Morphophysiological changes of the female prostate during pregnancy are still little known. Considering that this gland is highly influenced by steroid hormones, the aim of this study was to evaluate the impact of the pregnancy on female prostate morphophysiology in gerbils. Pregnant females were timed, and the prostates were analyzed at pregnancy days 6 (P6), 12 (P12), 18 (P18), and 24 (P24). Virgin females were used as the control group (C). We observed a profound change in the hormonal profile during gestation, which was marked by a high oscillation of the progesterone (P4) hormone. P4 serum levels increased, peaking at the middle of gestation, and decreased to the end of the pregnancy. The morphology of the gland in pregnant females also changed, being marked by an increase of acini lumen, and a decrease in stroma. Indeed, the acinar changes during pregnancy were followed by a significant reduction of the epithelial height, besides a change of the smooth muscle cells' morphology that became more relaxed. The number of progesterone receptor (PR) and androgen receptor (AR)-positives cells decreased with the increase of progesterone serum levels, showing an inverse relationship. Finally, we observed a reduction of epithelial proliferation and a significant increase of gland PAS-positive secretion at the end of pregnancy. Altogether, these results showed, for the first time, that the female prostate morphophysioloy is profoundly influenced by the gestational period, suggesting that the fluctuation of the P4 serum levels is the main factor influencing the gland during this period.

The number and periodicity of seizures induce cardiac remodeling and changes in micro-RNA expression in rats submitted to electric amygdala kindling model of epilepsy.

Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration.

Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils.

Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.

Design, synthesis and pharmacological assessment of new pyrazole compounds.

AIMS: This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. MAIN METHODS: The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall-Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. KEY FINDINGS: The synthesised compounds (5-7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall-Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.

Developmental changes induced by exogenous testosterone during early phases of prostate organogenesis.

The aim of this study was to evaluate the impact of prenatal testosterone exposure on prostate development in male and female neonatal gerbils. Pregnant females were exposed to subcutaneous injections of testosterone cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were then euthanized at postnatal day 1. Morphological analysis showed that females were severely affected by androgen exposure. We also observed that male and female urogenital sinus (UGS) responded differentially to testosterone treatment, demonstrating heterogeneous immunostaining for the androgen receptor (AR), estrogen receptor alpha (ERα), and proliferating cell nuclear antigen (PCNA). Smooth muscle α-actin (α-SMA) analysis showed that testosterone delays the myodifferentiation, allowing buds to reach the ectopic mesenchymes of the female UGS. Our data showed that abnormal testosterone exposure disrupted prostate organogenesis, altered the expression patterns of important markers, and demonstrated that female UGS was particularly influenced by androgen exposure during a critical window in the developmental period.

Photobiomodulation and Mandibular Advancement Modulates Cartilage Thickness and Matrix Deposition in the Mandibular Condyle.

Objective: We evaluated the effects of photobiomodulation (PBM), mandibular advancement (MA), and the combination of both treatments (PBM+MA) on condylar growth, by the analysis of cartilage and bone formation, fibrillar collagen deposition, proteoglycan content, cell proliferation, and clastic cell index (CCI). Methods: Forty male Wistar rats were randomly assigned to CONTROL, PBM, positive control-MA, and PBM+MA groups. The appliance was worn 10 h/day. Laser was irradiated bilaterally on mandibular condyles in 8 alternate days (1 irradiation point per condyle) using the following parameters: 780 nm, 10 J/cm2, 40 mW, 1 W/cm2, 10 sec/point, 0.4 J/point, and cumulative dose per point: 3.2 J. PBM+MA received both treatments simultaneously. After 15 days, the animals were euthanized and the condyles dissected and embedded in paraffin. Histological sections from the intermediate portion of the condyle were used for morphometric analysis. The relative frequency (%) of fibrillar collagens was determined in sections stained with picrosirius red-hematoxylin under polarized light or Gömöri's method for reticular fibers. Proteoglycan content was evaluated by computerized photocolorimetric analysis. CCI was determined by tartrate-resistant acid phosphatase (TRAP), and proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Results: PBM and MA influenced condylar cartilage thickeness and matrix deposition, but none of the treatments affected significantly the area of the condyle. CCI were not influenced by the treatments, but clastic cells distribution was influenced by MA and PBM+MA treatments. There was no significant difference in proliferating cells among the groups. Conclusions: This study demonstrated that PBM and MA stimulates matrix deposition and cartilage thickening in the mandibular condyle, but was not able to demonstrate a synergistic effect between the treatments. Additional studies should be conducted to evaluate the possible synergistic effect between PBM and MA.

"Prostate telocytes change their phenotype in response to castration or testosterone replacement".

Telocytes are CD34-positive cells with a fusiform cell body and long, thin cytoplasmic projections called telopodes. These cells were detected in the stroma of various organs, including the prostate. The prostate is a complex gland capable of undergoing involution due to low testosterone levels; and this condition can be reversed with testosterone replacement. Telocyte function in the mature prostate remains to be dermined, and it is not known whether telocytes can take place in tissue remodeling during prostate involution and regrowth. The present study employed structural, ultrastructural and immunohistochemical methods to investigate the telocyte's phenotypes in the ventral prostate (VP) from control (CT), castrated (CS) and testosterone replacement (TR) groups of adult male Wistar rats. Telocytes were found in the subepithelial, perimuscular and interstitical regions around glandular acini. Telocytes from CT animals have condensed chromatin and long and thin telopodes. In CS group, telocytes appeared quiescent and exhibited layers of folded up telopodes. After TR, telocytes presented loose chromatin, abundant rough endoplasmic reticulum and enlarged telopodes, closely associated with bundles of collagen fibrils. We called these cells "telocytes with a synthetic phenotype". As testosterone levels and glandular morphology returned toward to the CT group parameters, after 10 days of TR, these telocytes progressively switched to the normal phenotype. Our results demonstrate that telocytes exhibit phenotypic plasticity upon androgen manipulation and interact with fibroblast and smooth muscle cells to maintain glandular architecture in control animals and during tissue remodeling after hormonal manipulation.

Neuroprotective Effect of Caryocar brasiliense Camb. Leaves Is Associated with Anticholinesterase and Antioxidant Properties.

Pequi (Caryocar brasiliense) is an endemic species from Brazilian Cerrado, and their fruits are widely used in regional cuisine. In this work, a crude hydroalcoholic extract (CHE) of C. brasiliense leaves and its resulting fractions in hexane (HF), chloroform (CF), ethyl acetate (EAF), and butanol (BF) were investigated for their antioxidant properties and anticholinesterase activities. The antioxidant properties were evaluated by free radical scavenging and electroanalytical assays, which were further correlated with the total phenolic content and LC-MS results. The acetylcholinesterase and butyrylcholinesterase inhibitory activities were examined using Ellman's colorimetric method. The LC-MS analysis of EAF revealed the presence of gallic acid and quercetin. CHE and its fractions, EAF and BF, showed anticholinesterase and antioxidant activities, suggesting the association of both effects with the phenolic content. In addition, behavioral tests performed with CHE (10, 100, and 300 mg/kg) showed that it prevented mice memory impairment which resulted from aluminium intake. Moreover, CHE inhibited brain lipid peroxidation and acetyl and butyryl-cholinesterase activities and the extract's neuroprotective effect was reflected at the microscopic level. Therefore, the leaves of pequi are a potential source of phenolic antioxidants and can be potentially used in treatments of memory dysfunctions, such as those associated with neurodegenerative disorders.

Antioxidant and Neuroprotective Properties of Eugenia dysenterica Leaves.

Eugenia dysenterica ex DC Mart. (Myrtaceae), popularly known as "cagaita," is a Brazilian plant rich in polyphenols and other antioxidant compounds. Aiming to evaluate the potential use of cagaita in pathologies involving oxidative stress, such as neurodegenerative disorders, this study investigated its antioxidant potential and neuroprotective effect. Electrochemical approaches and aluminium-induced neurotoxicity were used to determine respectively in vitro and in vivo antioxidant properties of cagaita. Voltammetric experiments were carried out in a three-electrode system, whose working electrode consisted of glassy carbon. Male Swiss mice were administered with AlCl3 orally at a dose of 100 mg/kg/day and with cagaita leaf hydroalcoholic extract (CHE) at doses of 10, 100, and 300 mg/kg/day. The redox behavior of CHE presented similar features to that of quercetin, a widely known antioxidant standard. CHE prevented mouse memory impairment which resulted from aluminium intake. In addition, biochemical markers of oxidative stress (catalase, superoxide dismutase activity, and lipid peroxidation) were normalized by CHE treatment. The potential of CHE to prevent aluminium-induced neurotoxicity was reflected at the microscopic level, through the decrease of the number of eosinophilic necrosis phenotypes seen in treated groups. Moreover, the protective effect of CHE was similar to that of quercetin, which was taken as the standard. These findings showed that the CHE of cagaita leaves has a potential to protect the brain against oxidative-induced brain damage.

Effect of allantoin on experimentally induced gastric ulcers: Pathways of gastroprotection.

Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE2), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters of gastric acid secretion and attenuated both the vascular permeability and MPO activity. The levels of pro-inflammatory cytokines were also reduced, accompanied by a restoration of CAT activity and GSH levels. Notably, allantoin treatment preserved the gastric-adhered mucus and PGE2 levels after ethanol administration. Microscopic and ultrastructural analysis revealed that allantoin maintained tissue integrity and prevented morphological changes in cells caused by ethanol. In summary, we demonstrated for the first time that allantoin possesses gastroprotective activity through anti-inflammatory, anti-oxidative, antisecretory, and cytoprotective mechanisms. The antisecretory and cytoprotective mechanisms are probably associated with an increase in PGE2 levels.

Mas receptor contributes to pregnancy-induced cardiac remodelling.

Previous studies have demonstrated a protective effect of the Ang-(1-7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1-7)/Mas receptor on pregnancy-induced cardiac remodelling remains unknown. The objective of the present study was to evaluate the participation of the Mas receptor in the development of the cardiac hypertrophy and fibrosis induced by gestation. Female Wistar rats were divided in three groups: control, pregnant and pregnant treated with Mas receptor antagonist A-779. Wild-type (WT) and Mas-knockout (KO) mice were distributed in non-pregnant and pregnant groups. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. The medial part of the left ventricle (LV) was collected for histological analysis. Echocardiographic analysis was used to evaluate cardiac function. SBP was not changed by pregnancy or A-779 treatment in the Wistar rats. Pharmacological blockade or genetic deletion of Mas receptor attenuates the pregnancy-induced myocyte hypertrophy. The treatment with A-779 or genetic deletion of the Mas receptor increased the collagen III deposition in LV from pregnant animals without changing fibroblast proliferation. KO mice presented a lower ejection fraction (EF), fractional shortening (FS) and stroke volume (SV) and higher end systolic volume (ESV) compared with WT. Interestingly, pregnancy restored these parameters. In conclusion, these data show that although Mas receptor blockade or deletion decreases physiological hypertrophy of pregnancy, it is associated with more extracellular matrix deposition. These alterations are associated with improvement of cardiac function through a Mas-independent mechanism.