Anti-migratory and cytotoxic effect of indole derivative in C6 glioma cells.

Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC50 values were determined. Compound 9 exhibited the highest cytotoxic activity (IC50 = 0.4 µg/mL) in gliomas (C6 cell line), and were selected for further experiments. C6 cells were treated with compound 9 to evaluate cellular mechanisms such as colony formation and cell migration capacity and morphological alterations. Compound 9 decreased clone formation (0.4 and 0.8 µg/mL), and inhibited migration (0.2-0.8 µg/mL) in C6 cells. Morphological changes in cells treated with the compound 9 were also observed, such as chromatin condensation, and disorganization in cellular stress beams. Indole derivatives had a cytotoxic effect on tumor cells, and compound 9 showed the best anti-proliferative and anti-migratory activity in glioma cells.

Inhibitory effect of O-propargyllawsone in A549 lung adenocarcinoma cells.

BACKGROUND: Lung cancer is the deadliest type of cancer in the world and the search for compounds that can treat this disease is highly important. Lawsone (2-hydroxy-1,4-naphtoquinone) is a naphthoquinone found in plants from the Lawsone genus that show a high cytotoxic effect in cancer cell lines and its derivatives show an even higher cytotoxic effect. METHODS: Sulforhodamine B was used to evaluate the cytotoxic activity of compounds on tumor cells. Clonogenic assay was used to analyze the reduction of colonies and wound healing assay to the migratory capacity of A549 cells. Apoptosis and necrosis were analyzed by flow cytometer and Giemsa staining. Hemolysis assay to determine toxicity in human erythrocytes. RESULTS: Lawsone derivatives were evaluated and compound 1 (O-propargyllawsone) was the one with the highest cytotoxic effect, with IC50 below 2.5 µM in A549 cells. The compound was able to reduce colony formation and inhibit cell migration. Morphological changes and cytometry analysis show that the compound induces apoptosis and necrosis in A549 cells. CONCLUSIONS: These results show that O-propargyllawsone show a cytotoxic effect and may induce apoptosis in A549 cells.

Cytotoxic activity of essential oil from Leaves of Myrcia splendens against A549 Lung Cancer cells.

BACKGROUND: Plants of the Myrcia genus have been widely used in folk medicine to treat various diseases, including cancer. Myrcia splendens species has a diverse chemical constitution, but the biological activities of its essential oil have not been well investigated. In this study to out the chemistry characterization of essential oil (EO) from the leaves of the species M. splendens from Brazil and evaluate cytotoxic effect in A549 lung cancer cells. METHODS: M. splendens EO was obtained by hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). EO was isolated and evaluated for cellular viability in tumor cell lines by MTT assay. The evaluation of the formation of clones and the migratory capacity of the A549 cells treated with EO was done by the clonogenic assay and the wound healing assay. Morphological changes were observed in A549 cells by fluorescence using Phalloidin/FITC and DAPI. RESULTS: 22 compounds were identified in the chemical analysis of EO, corresponding to 88% of the sample. Major compounds were the sesquiterpenic hydrocarbons bicyclogermacrene (15.4%), germacrene D (8.9%) and E-caryophyllene (10.1%). The biological analysis of the EO showed high cytotoxic activity with an IC50 below 20 µg/ml in the THP-1, A549 and B16-F10 tumor cells. The treatment with EO reduced colony formation and inhibited the migratory capacity of A549 cells. Furthermore, apoptotic morphological changes in the nucleus and cytoplasm of A549 cells was observed after of treatment with EO. CONCLUSION: The findings of this study suggest that the M. splendens EO has cytotoxic compounds for the A549 lung cancer cells. Treatment with the EO decreased the colony formation and reduced the ability of lung cancer cells to migrate. Future studies may be used to isolate compounds from the EO for the study of lung cancer.

Lippia alba and Lippia gracilis essential oils affect the viability and oviposition of Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease that affects millions of people around the world. Currently, the only drug available for the treatment of this disease is praziquantel, which has low efficacy against immature helminth stages and there are reports of drug resistance. In this study, the chemical composition and the in vitro effect of essential oils (EOs) and major compounds from Lippia gracilis and Lippia alba against schistosomula and adult Schistosoma mansoni worms were evaluated. Adult S. mansoni worms cultured for 8h in the presence of L. gracilis EO (50 and 100 µg/mL) or for 2h with its major compound, carvacrol (100 µg/mL), had a 100% reduction in viability. After interaction with L. alba EO (100µg/mL), there was a reduction of approximately 60% in the viability of adult worms after 24 hours of exposure; citral (50 and 100 µg/mL), its major compound, reduced the viability after 24 hours by more than 75%. Treatment of schistosomula with 100 µg/mL of L. gracilis or L. alba EOs for 6h led to a reduction in parasite viability of 80% and 16% respectively. Both EOs and their major compounds significantly reduced the oviposition of adult worms exposed to a non-lethal concentration (5 µg/mL). In addition, morphological changes such as the destruction of the tegument and disorganization of the reproductive system of male and female worms were visualized. Both EOs showed low cytotoxicity at a concentration of 50 µg/mL. The results encourage further investigation of these plants as a potential source of bioactive compounds against S. mansoni.

Increased Accuracy to c-Fos-Positive Neuron Counting.

There is not a described method to count the core label of c-Fos-positive neurons, avoiding false-positive and false-negative results. The aim of this manuscript is to provide guidelines for a secure and accurate method to calculate a threshold to select which core of c-Fos-positive neurons marked by immunofluorescence has to be scored. A background percentage was calculated by dividing the intensity value (0 to 255) of the core of c-Fos-positive neurons by its surrounding background from the 8-bit images obtained in a previous study. Using the background percentage from 20% up to 98%, raising 2% once for each score, as threshold to choose which core has to be counted, a script was written for the R program to count the number of the c-Fos-positive neurons and the comparison between control and experimental groups. The differences of the average number of the core counted c-Fos-positive neurons between control and experimental groups, at all thresholds studied, showed a rising value related to an increase of the background percentage threshold as well as a decrease of its p value related to an increase of the threshold of background percentage. For the smallest thresholds (high intensity of label), the differences between groups are suppressed (false negative). However, for the biggest thresholds (nonspecific label), these differences are always the same (false positive). Therefore, to avoid the false-negative and the false-positive values, it was chosen as the threshold of 62% the inflection point of the linear regression, which is equally different from the biggest and smallest values of the differences between groups.

Anti-proliferative and pro-apoptotic activity of glycosidic derivatives of lawsone in melanoma cancer cell.

BACKGROUND: Melanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells. METHODS: The Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability. RESULTS: In pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI > 75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC50), and the compound 9, that has IC50 5.3 µM in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 µM concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells. CONCLUSIONS: The results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).

Effects of the solid lipid nanoparticle of carvacrol on rodents with lung injury from smoke inhalation.

The aim of this present study was to evaluate the effect of solid lipid nanoparticles (SLN) containing carvacrol over the lung damage of airway smoke inhalation. The study was conducted with 30 rats subjected to smoke inhalation and divided into 5 groups such as, normal control, negative control, oxygen group, SLN alone, and SLN+CARV group. The animals were sacrificed 24 h after the induction of inhalation injury further, the tissues of larynx, trachea, and lungs were collected for the histological, hematological, myeloperoxidase, and malondialdehyde analysis. The obtained results showed that treatment with CARV+SLN minimized the inhalation injury, since it reduced malondialdehyde significantly, when compared to the negative control group and minimized the histological changes which proves the absence of pulmonary emphysema and exudate in laryngeal and tracheal lumen in the CARV+SLN-treated group. Meanwhile, the presence of lesion with chronic characteristics was observed in the negative control and oxygen groups. It is suggested that the SLN containing carvacrol minimized oxidative stress and histological damages generated from smoke inhalation in rodents.

Inflammatory Mediators and Oxidative Stress in Animals Subjected to Smoke Inhalation: A Systematic Review.

BACKGROUND: The inhalation injury is usually initiated by uninhibited absorption of smoke, favoring the release of cytokines and other lipid mediators from inflammatory cells in lung airways and parenchyma. OBJECTIVES: To systematically review, examine, and synthesize the main inflammatory mediators analyzed in published studies in animals subjected to smoke inhalation, as well as oxidative stress. SEARCH STRATEGY: A comprehensive literature search was conducted through MEDLINE-PubMed, Web of Science, and Scopus. SELECTION CRITERIA: Studies with animals subjected to lung damage from smoke inhalation that evaluated the presence and the action of inflammatory mediators and oxidative stress. RESULTS: A total of 1332 studies were initially identified, with only 31 meeting the inclusion criteria. The inflammatory mediators and oxidative stress markers studied and presented in the articles described herein were varied; however, the most cited ones were tumor necrosis factor-alpha (6), IL-8 and IL-6 (both studied in five articles), IL-1ß and nuclear factor kappa ß (both studied in 4 articles), malondialdehyde (11 studies), and myeloperoxidase (7). It is worth noting that most studies evaluated more than one inflammatory mediator and oxidative stress marker. CONCLUSION: Based on this review, we could observe that the main inflammatory mediators and oxidative stress markers analyzed were TNF-α, IL-8, IL-6, IL-1ß, nuclear factor kappa ß, MDA, and MPO. However, it is necessary to increase the rigor of study design and data, in order to have studies that are more homogeneous and with appropriate methodological quality.

Preparation, Characterization, and Pharmacological Activity of Cymbopogon winterianus Jowitt ex Bor (Poaceae) Leaf Essential Oil of ß-Cyclodextrin Inclusion Complexes.

This study aimed to evaluate the orofacial antinociceptive effect of the Cymbopogon winterianus essential oil (LEO) complexed in ß-cyclodextrin (LEO-CD) and to assess the possible involvement of the central nervous system (CNS). The LEO was extracted, chromatographed, and complexed in ß-cyclodextrin. The complex was characterized by differential scanning calorimetry (DSC) and thermogravimetry derivative (TG/DTG). Male Swiss mice (2-3 months) were treated with LEO-CD (50-200 mg/kg, p.o.), vehicle (distilled water, p.o.), or standard drug (i.p.) and subjected to the orofacial nociception formalin-, capsaicin-, and glutamate-induced. After the formalin test, the animals were perfused and the brains subjected to immunofluorescence for Fos. The rota-rod test (7 rpm/min) was carried out. Geraniol (37.57%) was the main compound of LEO. DSC and TG/DTG proved the complexation. The orofacial nociceptive behavior was significantly (p < 0.05) reduced. The number of Fos-positive cells was significantly changed in the dorsal raphe nucleus (p < 0.01), locus coeruleus (p < 0.001), trigeminal nucleus (p < 0.05), and trigeminal thalamic tract (p < 0.05). LEO-CD did not cause changes in motor coordination in the rota-rod test. Thus, our results suggested that LEO-CD has an orofacial antinociceptive profile, probably mediated by the activation of the CNS without changing the motor coordination.

Citronellol, a natural acyclic monoterpene, attenuates mechanical hyperalgesia response in mice: Evidence of the spinal cord lamina I inhibition.

We evaluated the anti-hyperalgesic effect of citronellol (CT) and investigated the spinal cord lamina I involvement in this effect. Male mice were pre-treated with CT (25, 50 and 100mg/kg, i.p.), indomethacin (10mg/kg, i.p.), dipyrone (60mg/kg, i.p.) or vehicle (saline+Tween 80 0.2%). Thirty minutes after the treatment, 20µL of carrageenan (CG; 300µg/paw), PGE2 (100ng/paw), dopamine (DA; 30µg/paw) or TNF-α (100pg/paw) were injected into the hind paw subplantar region and the mechanical threshold was evaluated with an electronic anesthesiometer. The CT effect on edema formation was evaluated after the right paw subplantar injection of CG (40µL; 1%) through the plethysmometer apparatus. To evaluate the CT action on the spinal cord, the animals were treated with CT (100mg/kg; i.p.) or vehicle (Saline+Tween 80 0.2%; i.p.) and, after 30min, 20µL of CG (300µg/paw; i.pl.) was injected. Ninety minutes after the treatment, the animals were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein. CT administration produced a significantly reduction (p<0.05) in the mechanical hyperalgesia induced by CG, TNF-α, PGE2 and DA when compared with control group. The treatment with CT also significantly (p<0.05) decreased the paw edema. The immunofluorescence showed that the CT decrease significantly (p<0.05) the spinal cord lamina I activation. Thus, our results provide that CT attenuates the hyperalgesia, at least in part, through the spinal cord lamina I inhibition.

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines.

CONTEXT: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment. OBJECTIVE: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

Evidence for the involvement of descending pain-inhibitory mechanisms in the attenuation of cancer pain by carvacrol aided through a docking study.

AIMS: The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice. MAIN METHODS: Carvacrol treatment (12.5-50mg/kgs.c.) once daily for 15days was started 24h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABAA receptors. KEY FINDINGS: CARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABAA. SIGNIFICANCE: Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain.

Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom.

Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

ß-cyclodextrin complex containing Lippia grata leaf essential oil reduces orofacial nociception in mice - evidence of possible involvement of descending inhibitory pain modulation pathway.

The treatment of orofacial pain remains a major challenge for modern medicine. Thus, we prepared and physicochemically characterized a new ß-cyclodextrin complex containing Lippia grata leaf essential oil (ß-CD/EO) to investigate their possible antinociceptive activity in animal models of orofacial pain. The results of Differential scanning calorimeter (DSC) and Thermogravimetry/derivative thermogravimetry (TG/DTG) showed that the products prepared by Slurry complexation (SC) method were able to incorporate greater amounts of EO. In the X-ray diffractogram, it was shown that complex between EO and ß-CD was formed. Male Swiss mice were pre-treated with ß-CD/EO (6, 12 or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.) or vehicle (distilled water, p.o.) 1 hr before treatment with formalin (20 µL, 2%), capsaicin (20 µL, 2.5 µg) or glutamate (40 µL, 25 µM) into the right upper lip. Our results demonstrated that p.o. treatment with ß-CD/EO was significantly (p < 0.05 or p < 0.001) capable of reducing the nociceptive face-rubbing behaviour in both phases of the formalin test. ß-CD/EO-treated mice were also significantly (p < 0.05 or p < 0.001) protected against nociception induced by capsaicin and glutamate. For the action in the central nervous system (CNS), ninety minutes after the treatment, the mice were perfused, the brains collected, crioprotected, cut in a criostate and submitted to an immunofluorescence protocol for Fos protein. The immunofluorescence protocol demonstrated that the ß-CD/EO significantly activated (p < 0.05; p < 0.01 or p < 0.001) the motor cortex, the Locus ceruleus, the nucleus raphe magnus and the periaqueductal gray of the CNS. These effects apparently did not alter, in tested doses, the motor coordination of mice in the rota-rod test. Our results proposed that ß-CD/EO might present an important draft of drug to the study of new compounds for the treatment of orofacial pain.

The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) reduces urinary bladder damage during cyclophosphamide-induced cystitis in rats.

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100-400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx- were also evaluated. Treatment with EECp (100-400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx- induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats.

ß-Cyclodextrin-complexed (-)-linalool produces antinociceptive effect superior to that of (-)-linalool in experimental pain protocols.

Many plants produce (-)-linalool, a plant-derived monoterpene alcohol, including members of the Lamiaceae (mints) and Lauraceae family (laurels, cinnamon, rosewood). The anti-inflammatory and analgesic effects of (-)-linalool have been widely suggested for various studies. Poor chemical stability and short half-life restrain the clinical applications of some essential oil and monoterpenes, including (-)-linalool. However, ß-cyclodextrin (ß-CD) has been used to increase solubility and stability of lipophilic compounds and also to improve the pharmacological effects. In this study, the antinociceptive effect of (-)-linalool and (-)-linalool/ß-CD was examined using the acetic acid writhing reflex, formalin and hotplate tests in rodents. (-)-Linalool and (-)-linalool/ß-CD demonstrated strong antinociceptive activity in all the chemical- and heat-induced mice models (p < 0.01 or p < 0.001). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. In peritonitis induced by carrageenan, isolated monoterpene or ß-CD complex also reduced total leucocyte migration and TNF-α levels in peritoneal fluid. The inclusion complexes, (-)-linalool/ß-CD, revealed that the antinociceptive effect was significantly (p < 0.01) improved when compared with (-)-linalool alone. Such results were unlikely to be provoked by any motor abnormality. Together, our results suggest that ß-CD might represent an important tool for improvement of analgesic and anti-inflammatory profiles of (-)-linalool and other water-insoluble compounds, such as lipophilic monoterpenes or essential oils.

Citronellol reduces orofacial nociceptive behaviour in mice - evidence of involvement of retrosplenial cortex and periaqueductal grey areas.

Citronellol (CT) is a monoterpenoid alcohol present in the essential oil of many medicinal plants, such as Cymbopogon citratus. We evaluated the antinociceptive effects of CT on orofacial nociception in mice and investigated the central pathway involved in the effect. Male Swiss mice were pretreated with CT (25, 50 and 100 mg/kg, i.p.), morphine (5 mg/kg, i.p.) or vehicle (saline + tween 80 0.2%). Thirty minutes after the treatment, we injected formalin (20 µl, 2%), capsaicin (20 µl, 2.5 µg) or glutamate (40 µl, 25 µM) into the right limb. For the action in the CNS, ninety minutes after the treatment, the animals were perfused, the brains collected, crioprotected, cut in a criostate and submitted in an immunofluorescence protocol for Fos protein. CT produced significant (p < 0.01) antinociceptive effect, in all doses, in the formalin, capsaicin and glutamate tests. The immunofluorescence showed that the CT activated significantly (p < 0.05) the olfactory bulb, the piriform cortex, the retrosplenial cortex and the periaqueductal grey of the CNS. Together, our results provide first-time evidence that this monoterpene attenuates orofacial pain at least, in part, through an activation of CNS areas, mainly retrosplenial cortex and periaqueductal grey.

Absorption levels and morphological features of fetal organs in wistar rats treated with lead acetate / Niveles de absorción y características morfológicas de los órganos fetales en ratas wistar tratadas con acetato de plomo

Lead is one of the heavy metals most used in industry. Poisoning due to long-term lead exposure is known as saturnism, and is an occupational illness that has been known for many years. Lead is highly toxic and can compromise the structural and functional patterns of organs and systems. The aim of this study was to examine the lungs and kidneys of fetuses from female Wistar rats exposed to lead acetate. In this study, the lungs and kidneys of 20 fetuses from female rats that had previously been treated with lead acetate were dissected, fixed, embedded in paraffin and stained with hematoxylin and eosin. Macroscopic changes to the shape, color and consistency of organs from fetuses treated with this heavy metal were observed, in comparison with organs from control fetuses. Microscopic lesions characterized by vascular sclerosis, cell atrophy or hyperplasia, progressive interstitial fibrosis, inclusion bodies containing lead acetate and glomerular sclerosis were found in the kidneys. The lesions found in the lungs consisted of destructuring of the parenchyma, impregnation with lead acetate, formation of fibrosis, extravasation of vascular fluids, reduction of the alveolar spaces and formation of alveolar edema. These changes were correlated with the level of lead acetate absorption, as determined using atomic spectrophotometry.

El plomo es un metal pesado utilizado en la industria. El envenenamiento debido a la exposición prolongada por plomo es una enfermedad profesional conocida por muchos años. La toxicidad del plomo es muy expresiva y puede poner en peligro el modelo estructural y funcional de los órganos y sistemas. El objetivo de este estudio fue examinar los pulmones y riñones de fetos de ratas Wistar expuestos al acetato de plomo. En este estudio, 20 fetos de ratas Wistar previamente tratados con acetato de plomo durante la gestación, tuvieron sus órganos disecados, fijados, incluidos en parafina y teñidos con hematoxilina y eosina. Macroscópicamente, los órganos fetales tratados por este metal fueron comparados con los órganos de fetos controles en relación a forma, color y consistencia. Microscópicamente, se encontraron lesiones en el riñón que se caracterizaron por esclerosis vascular, atrofia o hiperplasia de células, fibrosis intersticial progresiva, presencia de cuerpos de inclusión que contenían acetato de plomo y esclerosis glomerular. En el pulmón se observó desorganización del parénquima impregnado con acetato de plomo, formación de fibrosis, líquido intersticial, reducción de los espacios alveolares y edema alveolar. Estos cambios se correlacionaron con el nivel de absorción de acetato de plomo, determinado por espectrometría atómica.

Angiotensinergic pathway through the median preoptic nucleus in the control of oxytocin secretion and water and sodium intake.

Our objective was to study in which situations the median preoptic nucleus (MnPO) interferes with the control of oxytocin secretion and salt intake and the possible mediation of angiotensin II (AII) through their AT1 receptors. Lesion of the MnPO by ibotenic acid in male rats did not change water and NaCl intake in conditions of ad libitum offer, water deprivation or salt load, but it did cause significant decrease of NaCl intake in sodium depleted animals. These animals presented higher water intake or lower NaCl intake after microinjection of AII or losartan into the MnPO, respectively. They decreased plasma oxytocin after microinjection of losartan into the MnPO, but not of AII or isotonic saline. Oxytocin secretion induced by hypertonic saline i.p. was reduced by microinjection of AII, but not losartan into the MnPO. On the other hand, microinjection of losartan in this area, but not AII, reduced plasma oxytocin in animals submitted to the isotonic saline i.p. Thus, it seems that the sodium intake control is performed by MnPO neurons through the stimulatory action of angiotensin II on AT1 receptors under sodium depletion, but not water deprivation or salt overload neither of ad libitum water and salt intake condition. On the other hand, in the high-sodium condition, endogenous angiotensin did not act on MnPO neurons to the control of oxytocin secretion while exogenous angiotensin inhibited oxytocin secretion. These results indicate two possible angiotensinergic neural circuits: one is stimulating and the other is inhibiting oxytocin secretion, depending on sodium balance.