Flaxseed Oil (Linum usitatissimum) Prevents Cognitive and Motor Damage in Rats with Hyperammonemia.

Hyperammonemia is characterized by the excessive accumulation of ammonia in the body as a result of the loss of liver detoxification, leading to the development of hepatic encephalopathy (HE). These metabolic alterations carry cognitive and motor deficits and cause neuronal damage, with no effective treatment at present. In this study, we aimed to evaluate the effect of two subacute oral administrations of flaxseed oil (0.26 and 0.52 mL/kg) on short- and long-term memory, visuospatial memory, locomotor activity, motor coordination, and the neuronal morphology of the prefrontal cortex (PFC) via tests on Wistar rats with hyperammonemia. The goal was to identify its role in the regulation of cerebral edema, without liver damage causing cerebral failure. In contrast with an ammonium-rich diet, flaxseed oil and normal foods did not cause cognitive impairment or motor alterations, as evidenced in the short-term and visuospatial memory tests. Furthermore, the flaxseed oil treatment maintained a regular neuronal morphology of the prefrontal cortex, which represents a neuroprotective effect. We conclude that the oral administration of flaxseed oil prevents cognitive and motor impairments as well as neuronal alterations in rats with hyperammonemia, which supports the potential use of this oil to ameliorate the changes that occur in hepatic encephalopathy.

Participation of the Serotonergic System and Brain-Derived Neurotrophic Factor in the Antidepressant-like Effect of Flavonoids.

Depressive disorders are among the most disabling diseases experienced around the world, and their incidence has significantly increased over the last few decades due to multiple environmental, social, and biological factors. The search for new pharmacological alternatives to treat depression is a global priority. In preclinical research, molecules obtained from plants, such as flavonoids, have shown promising antidepressant-like properties through several mechanisms of action that have not been fully elucidated, including crossing of the blood brain barrier (BBB). This review will focus on discussing the main findings related to the participation of the serotonergic system and brain-derived neurotrophic factor (BDNF) on the antidepressant-like effect of some flavonoids reported by behavioral, neurochemical, and molecular studies. In this sense, evidence shows that depressive individuals have low levels of serotonin and BDNF, while flavonoids can reverse it. Finally, the elucidation of the mechanism used by flavonoids to modulate serotonin and BDNF will contribute to our understanding of the neurobiological bases underlying the antidepressant-like effects produced by these natural compounds.

Landfill Leachate from an Urban Solid Waste Storage System Produces Genotoxicity and Cytotoxicity in Pre-Adolescent and Young Adults Rats.

Landfill leachate is a complex mixture of organic and inorganic molecules, as well as environmental pollutants that can cause harm to ecosystems and living beings. The micronucleus test in peripheral blood erythrocytes was used to evaluate the genotoxic and cytotoxic effects of exposure to a landfill leachate from an outdoor solid waste storage system on Wistar strain rats at different developmental stages, pre-adolescents and young adults, and the heavy metal content of the leachate was determined by atomic absorption spectrometry. Contents of arsenic, cadmium, chromium, mercury, and lead in the landfill leachate were outside the allowable international standards, and the exposure to the landfill leachate caused genotoxic and cytotoxic effects on Wistar rats, where the pre-adolescent animals were more susceptible to the toxics contained in the landfill leachate than young adults. Heavy metals contained in landfill leachate, individually or synergically with other molecules can be responsible for clastogenic and cytotoxic effects that can be harmful to humans and ecosystems.

Zebrafish as a Useful Tool in the Research of Natural Products With Potential Anxiolytic Effects.

Zebrafish (Danio rerio) is a popular and valuable species used in many different biomedical research areas. The complex behavior that fish exhibit in response to different stimuli allows researchers to explore the biological and pharmacological basis of affective and mood disorders. In this sense, anxiety is commonly studied in preclinical research with animal models in rodents. During the last decade, those models have been successfully adapted to zebrafish. Stressful stimuli, such as novel environments, chemical substances, light conditions, and predator images, can trigger defensive behaviors considered indicators of an anxiety-like state. In the first stage, models were adapted and validated with different stressors and anxiolytic drugs with promising results and are now successfully used to generate scientific knowledge. In that sense, zebrafish allows several routes of administration and other methodological advantages to explore the anxiolytic effects of natural products in behavioral tests as novel tank, light-dark chamber, and black/white maze, among others. The present work will review the main findings on preclinical research using adult zebrafish to explore anxiolytics effects of natural products as plant secondary metabolites such as flavonoids, alkaloids and terpenes or standardized extracts of plants, among others. Scientific literature confirms the utility of zebrafish tests to explore anxiety-like states and anxiolytic-like effects of plant secondary metabolites, which represent a useful and ethical tool in the first stages of behavioral.

Anxiolytic-like effect of the aqueous extract of Justicia spicigera leaves on female rats: A comparison to diazepam.

BACKGROUND: In Mexico, an infusion made from muicle (Justicia spicigera, Mexican honeysuckle) is used to treat menstrual problems and soothe people's "nerves" (i.e., anxiety and/or depression). However, no studies have yet substantiated these affects. Anxiety currently ranks as the seventh most common cause of disability worldwide, a fact that has intensified the search for new treatments with fewer adverse effects and better therapeutic efficacy. OBJECTIVE: The anxiolytic-like effect of the aqueous extract of muicle leaves (AEML) was analyzed, and the influence of the estrous cycle on its pharmacological effect in rats was explored. METHODS: Female Wistar rats were subjected to the elevated plus maze test to evaluate the anxiolytic effect, followed by an assessment of locomotor activity using the open field test. Diazepam was the reference drug used. Preliminary phytochemical tests were performed. RESULTS: The dose of 12  mg/kg of AEML increased the time to first entry, and the frequency of entries into, the open arms in the proestrus-estrus (P-E) and metestrus-diestrus phases (M-D), while also reducing the anxiety index in the P-E phases. These effects are similar to those observed with diazepam on the elevated plus maze test. None of the treatments showed effects on locomotor activity. The presence of flavonoids, sterols and terpenes in the AEML was confirmed. CONCLUSION: The anxiolytic-like effect of the dose of 12  mg/kg of AEML in the P-E phases could be due to the presence of the metabolites identified; i.e., flavonoids, sterols and/or terpenes.

Efecto hepatoprotector de una mezcla de siete plantas en cirrosis inducida con tetracloruro de carbono / Hepatoprotective effect of a mixture of seven plants in carbon tetrachloride induced cirrhosis

Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

Efecto hepatoprotector de una mezcla de siete plantas en cirrosis inducida con tetracloruro de carbono / Hepatoprotective effect of a mixture of seven plants in carbon tetrachloride induced cirrhosis

Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

Hormone replacement with 17ß-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17ß-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17ß-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17ß-estradiol levels, and the role of testosterone, 17ß-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17ß-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17ß-estradiol +5-α-dihydrotestosterone, but not testosterone.

Altered expression of 5-HT1A receptors in adult rats induced by neonatal treatment with clomipramine.

Chronic administration of clomipramine (CMI) to neonatal rats produces behaviors that resemble a depressive state in adulthood. Dysfunctions in the activity of the central nervous system's serotonergic function are important in understanding the pathophysiology of depression. The serotonin system is implicated in major depression and suicide and is negatively regulated by somatodendritic 5-HT1A autoreceptors. Desensitization of 5-HT1A autoreceptors is implicated in the long latency of some antidepressant treatments. Alterations in 5-HT1A receptor levels are reported in depression and suicide. In this study, we analyzed the effect of neonatal administration of CMI on the activity of 5-HT1A receptors, both pre- and post-synaptically, by administering an agonist of 5-HT1A receptors, 8-OH-DPAT, and then subjecting the rats to the forced swimming test (FST) a common procedure used to detect signs of depression in rats. Also measured were levels of the mRNA expression of 5-HT1A receptors in the dorsal raphe (DR), the hypothalamus and the hippocampus. Wistar rats were injected twice daily with CMI at doses of 15mgkg(-1) or saline as vehicle (CON) via s.c. from postnatal day 8 for 14days. At 3-4months of age, one set of rats from each group (CON, CMI) was evaluated for the effect of a selective agonist to the 5-HT1A receptor subtype, 8-OH-DPAT, by testing in the FST. Also determined was the participation of the pre- or post-synaptic 5-HT1A receptor in the antidepressant-like action of 8-OH-DPAT. This involved administering an inhibitor of tryptophan hydroxylase, parachlorophenylalanine (PCPA), and pretreatment with 8-OH-DPAT before the FST test and to evaluate the rectal temperature and locomotor activity. The expression of the mRNA of the 5-HT1A receptors was examined in the dorsal raphe nucleus, the hypothalamus and the hippocampus using the semi-quantitative RT-PCR method. The results from this study corroborate that neonatal treatment with clomipramine induces a pronounced immobility in the FST when animals reach adulthood, manifested by a significant decrease in swimming behavior, though counts of climbing behavior were not modified. This effect was similar in magnitude when 8-OH-DPAT was administered to CON group. Furthermore, the administration of 8-OH-DPAT induces a significant and similar increase in rectal temperature and locomotor activity in both the CON as in the CMI group. Neonatal treatment with CMI resulted in a significant decrease in the expression of the mRNA of the 5-HT1A receptors in the DR (% more than vehicle) in adulthood. In the case of the postsynaptic receptors located in the hypothalamus and hippocampus, neonatal treatment with CMI induced a significant increase in the mRNA expression of the 5-HT1A receptors. These data suggest that neonatal treatment with CMI induces a downregulation of the mRNA of the 5-HT1A autoreceptors in the DR, and an increment in the expression of the postsynaptic 5-HT1A receptors. The results after the administration of PCPA and 8-OH-DPAT on FST, rectal temperature and locomotor activity for both groups suggest that the function of postsynaptic receptors remains unchanged. All together these data show that the depressive behavior observed in adulthood in this animal model may be associated with long-term alterations in the expression of the mRNA of the 5-HT1A receptors.

Prefrontal serotonergic denervation induces increase in the density of 5-HT2A receptors in adult rat prefrontal cortex.

The 5-HTergic system and particularly 5-HT(2A) receptors have been involved in prefrontal cognitive functions, but the underlying mechanisms by which the serotonin (5-HT) system modulates these processes are still unclear. In this work, the effects of prefrontal 5-HTergic denervation on the density and expression levels of 5-HT(2A) receptors were evaluated by immunohistochemical and molecular biology studies in the prefrontal cortex (PFC). The [(3)H]-Ketanserin binding study revealed an increase in the B(max), along with no change in the binding affinity (K(D)) for 5-HT(2A) receptors. The increase in PFC of 5-HT(2A) receptor density in response to denervation was accompanied by increase in 5-HT(2A) receptor mRNA and protein levels. This increase in the number of 5-HT(2A) receptors may be interpreted as an adaptive plastic change, i.e., hypersensitivity; resulting from the selective pharmacological lesion of the raphe-proceeding 5-HTergic fibers to the PFC. Based on previous evidence, this could be strongly related to the abnormal expression of short-term memory.