Giardia lamblia is a worldwide protozoan responsible for a significant number of intestinal infections. There are several drugs for the treatment of giardiasis, but they often cause side effects. Curcumin, a component of turmeric, has antigiardial activity; however, the molecular target and mechanism of antiproliferative activity are not clear. The effects of curcumin on cellular microtubules have been widely investigated. Since tubulin is the most abundant protein in the cytoskeleton of Giardia, to elucidate whether curcumin has activity against the microtubules of this parasite, we treated trophozoites with curcumin and the cells were analyzed by scanning electron microscopy and confocal microscopy. Curcumin inhibited Giardia proliferation and adhesion in a time-concentration-dependent mode. The higher inhibitory concentrations of curcumin (3 and 15μM) disrupted the cytoskeletal structures of trophozoites; the damage was evident on the ventral disk, flagella and in the caudal region, also the membrane was affected. The immunofluorescence images showed altered distribution of tubulin staining on ventral disk and flagella. Additionally, we found that curcumin caused a clear reduction of tubulin expression. By docking analysis and molecular dynamics we showed that curcumin has a high probability to bind at the interface of the tubulin dimer close to the vinblastine binding site. All the data presented indicate that curcumin may inhibit Giardia proliferation by perturbing microtubules.
One of the main concerns regarding organophosphate pesticides (OP) is their possible toxic effects. Doses that do not produce acute toxicity are capable of altering the structure and biochemistry of different tissues and organs by production of reactive oxygen species (ROS). Curcumin (CUR) is the main substance in Curcuma longa (Zingiberacea) rhizome that has strong antioxidant activity. However, the neuroprotective properties of curcumin against oxidative stress induced by prolonged exposure to parathion (PAR) is not clear. The present work evaluated the protective effect of curcumin against the oxidative damage induced in the rat hippocampus by the OP PAR. Forty female Wistar rats were distributed in four groups as follows: exposed to PAR by inhalation (PAR group); pre-treated with CUR and then exposed to PAR by inhalation, (CUR + PAR group); exposed to environmental air and treated with CUR in the food (CUR group); and exposed to environmental air (the control group). At the end of the handling process, the concentration of erythrocyte cholinesterase was monitored, as indicator of PAR intoxication and lipoperoxidation, immunohistochemistry for astrocytes, and activated microglia and apoptosis was determined in the hippocampus. In the present study, we show that the administration of CUR (200 mg/kg body weight) significantly diminished the oxidative damage in the hippocampus of rats exposed to the OP PAR. These data suggest that CUR may be an alternative to prevent neurodegenerative damage after pesticide exposure.
Millions of people around the world are exposed to air pollutants, such as particulate matter 2.5 (PM2.5) and ozone (O3). Such exposure usually does not exclude these two types of pollutants and their harmful effects could be additive or synergistic. O3 is a highly oxidizing gas that reacts with the cellular environment just as PM2.5, triggering nitrooxidative damage. Once nitrooxidative stress overcomes the endogenous antioxidant system, an acute neuroinflammatory process is generated, and once it becomes chronic, it favors the formation of neurodegenerative disease markers. The presence of these markers becomes potentially dangerous in people who have a genetic predisposition and are at a higher risk of developing neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Our experimental approach for nitrooxidative damage and neuroinflammation caused by air pollutants has focused on the exposure of rats to O3 in an isolated chamber. The hippocampus is the most studied brain structure because of its neuronal connectivity network with the olfactory epithelium, its weak antioxidant defense, and its fundamental roll in cognitive processes. However, other brain structures may exhibit a different degree of damage upon exposure to O3 and PM2.5, making their involvement an important factor in developing other CNS diseases. The age spectrum for augmented sensibility to air pollutants seems to mostly affect the pre-postnatal (autism spectrum) period and the elderly (neurodegenerative). Thus, a new approach could be the estimation of the damage caused by PM2.5 and O3 through a controlled exposure paradigm to determine the extent of damage caused by both pollutants.
30 December 2018 in Oxidative Medicine and Cellular Longevity
Ozone is a harmful tropospheric pollutant, causing the formation of reactive oxygen and nitrogen species that lead to oxidative damage in living beings. NF-κB can be activated in response to oxidative damage, inducing an inflammatory response. Nowadays, there are no reliable results that consolidate the use of antioxidants to protect from damage caused by ozone, particularly in highly polluted cities. Curcumin has a strong antioxidant activity and is a potent inhibitor of NF-κB activation with no side effects. The aim of this study is to evaluate the effect of curcumin in preventive and therapeutic approaches against oxidative damage, NF-κB activation, and the rise in serum levels of IL-1β and TNF-α induced by acute and chronic exposure to ozone in rat hippocampus. One hundred male Wistar rats were distributed into five groups; the intact control, curcumin-fed control, the ozone-exposed group, and the preventive and therapeutic groups. These last two groups were exposed to ozone and received food supplemented with curcumin. Lipid peroxidation was determined by spectrophotometry, and protein oxidation was evaluated by immunodetection of carbonylated proteins and densitometry analysis. Activation of NF-κB was assessed by electrophoretic mobility shift assay (EMSA), and inflammatory cytokines (IL-1β and TNF-α) were determined by ELISA. Curcumin decreased NF-κB activation and serum levels of inflammatory cytokines as well as protein and lipid oxidation, in both therapeutic and preventive approaches. Curcumin has proven to be a phytodrug against the damage caused by the environmental exposure to ozone.