ABSTRACT
Lead (Pb) exposure induces testicular damage and infertility. The aim of this study was to analyze and compare the therapeutic effects of antioxidants or vitamin D and calcium, which have previously been shown to reduce the toxic effects of Pb co-exposure, in rats. Rats were exposed to Pb for 28 days and subsequently treated with antioxidant (melatonin, silymarin), vitamin D and calcium (VitDCa) or a combination (melatonin or silymarin with VitDCa) for 28 days. Control groups included untreated rats (no Pb exposure or therapy), rats exposed only to melatonin or silymarin and rats exposed to Pb without post exposure therapy. Pb exposure induced testicular damage, increased blood lead level (BLL) and reduced serum testosterone level (STL). Rats exposed to Pb and left untreated for 28 days showed persistent pathological testicular alterations. The two treatments that were most effective in reversing pathological testis damage and restoring spermatogenesis were melatonin and silymarin. However, silymarin and melatonin treatment resulted in significantly different serum testosterone levels in rats. Whereas melatonin therapy reduced serum testosterone to levels lower than those in control rats, silymarin increased serum testosterone to levels higher than those in controls. Our pathological analysis of testes revealed that melatonin promoted spermatogenesis and regression of Pb exposure-induced degenerative changes, despite the associated reduction in serum testosterone levels. This result suggests that circulating testosterone may not have an important role in spermatogenesis. Collectively, our results suggest that melatonin and silymarin are effective therapies against the toxic effects Pb exposure in the male reproductive system.
Subject(s)
Melatonin , Silymarin , Rats , Male , Animals , Testis , Lead/toxicity , Melatonin/pharmacology , Melatonin/therapeutic use , Melatonin/metabolism , Calcium/metabolism , Antioxidants/pharmacology , Testosterone/metabolism , Silymarin/metabolism , Silymarin/pharmacology , Vitamin D/metabolism , Vitamin D/pharmacology , Oxidative StressABSTRACT
Kidney injury molecule-1 (KIM-1) is a membrane receptor upregulated in the proximal tubule cells following various types of kidney injuries. Notably, studies have suggested a correlation between KIM-1 expression and extracellular signal-regulated kinase (ERK) activation. In this study, we aimed to investigate the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and increased urinary KIM-1 levels in rats exposed to gentamicin or lead acetate, both at the end of toxic exposure and after a 4-week recovery period. Although other proteins were evaluated, only kidney overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels. For both toxic substances, the increased urinary KIM-1 levels corresponded with kidney inflammation. Our results suggest that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances that induce proximal tubule damage.
Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/urine , Cell Adhesion Molecules/urine , Extracellular Signal-Regulated MAP Kinases/metabolism , Gentamicins/toxicity , Kidney Tubules, Proximal/injuries , Kidney Tubules, Proximal/metabolism , Organometallic Compounds/toxicity , Signal Transduction/drug effects , Animals , Calcium Channels/metabolism , Cation Transport Proteins/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cytoplasm/metabolism , Disease Models, Animal , Histones/metabolism , Male , Phosphorylation , Rats , Rats, Wistar , TRPV Cation Channels/metabolismABSTRACT
Latua pubiflora (Griseb) Phil. Is a native shrub of the Solanaceae family that grows freely in southern Chile and is employed among Mapuche aboriginals to induce sedative effects and hallucinations in religious or medicine rituals since prehispanic times. In this work, the pentobarbital-induced sleeping test and the elevated plus maze test were employed to test the behavioral effects of extracts of this plant in mice. The psychopharmacological evaluation of L. pubiflora extracts in mice determined that both alkaloid-enriched as well as the non-alkaloid extracts produced an increase of sleeping time and alteration of motor activity in mice at 150 mg/Kg. The alkaloid extract exhibited anxiolytic effects in the elevated plus maze test, which was counteracted by flumazenil. In addition, the alkaloid extract from L. pubiflora decreased [3H]-flunitrazepam binding on rat cortical membranes. In this study we have identified 18 tropane alkaloids (peaks 1-4, 8-13, 15-18, 21, 23, 24, and 28), 8 phenolic acids and related compounds (peaks 5-7, 14, 19, 20, 22, and 29) and 7 flavonoids (peaks 25-27 and 30-33) in extracts of L. pubiflora by UHPLC-PDA-MS which are responsible for the biological activity. This study assessed for the first time the sedative-anxiolytic effects of L. pubiflora in rats besides the high resolution metabolomics analysis including the finding of pharmacologically important tropane alkaloids and glycosylated flavonoids.
ABSTRACT
Antecedentes. El asma y la rinitis se han convertido en las enfermedades alérgicas más prevalentes en la población infantil en el mundo. Objetivos. Determinar la prevalencia y el comportamiento epidemiológico de las enfermedades alérgicas en preescolares de la ciudad de Cali. Diseño. Estudio de corte transversal. Métodos. Se seleccionó una muestra de 198 niños preescolares menores de 6 años y se aplicó el cuestionario ISAAC. Resultados. La prevalencia de asma fue 20.6/100 y de rinitis alérgica 18.1/100 y su comportamiento diferente, presentándose con más frecuencia el asma en niños de estratos bajos 27/100 vs 13/100 en estratos altos. En cambio, en niños de estrato alto la rinitis fue más prevalente (29.3/100 vs 8.1/100, p=0.0002). El antecedente familiar de alergia fue más frecuente en los niños con asma que con rinitis (40.9/100 vs 9.1, p<0.008). No se encontró asociación entre género, edad o padres fumadores, con alguna de las enfermedades alérgicas
