RESUMEN
Monocytes and muscles demonstrate functionally contrasting behavior under conditions of zinc deficiency with relation to zinc storage system (muscle retain zinc in contrast to monocytes). We aimed to understand the effects of zinc status and HIV-1 Tat mediated inflammation on expression of zinc transporters in these types of cells. Expression of zinc transporters [ZnTs, ZIPs, and metallothionein (MT)] was quantified by qRT-PCR in RD, THP-1 cells separately and in co-cultured THP-1-RD cells. ZnT1 protein expression levels were confirmed by Western blot. Significant increase of MT and ZnT1 mRNA in response to zinc supplementation and decrease during zinc deficiency indicates significance of the genes encoding transporters in maintaining zinc homeostasis in these tissues. In the RD cells ZIP10 exhibited inverse relation to zinc status whereas no correlation was found in the THP-1 cells. Tat-induced inflammation resulted in the significant elevation of MT, IL6, ZIP7, ZIP8, ZIP9 transcripts in the co-cultured RD cells, whereas THP-1 cells demonstrated increased IL-1ß levels and reduced levels of ZIP7 and ZIP14. Zinc status and HIV-1Tat induced inflammation appear to influence differential expression of MT, ZnTs, and ZIPs in the muscle and monocyte cells.
Asunto(s)
Proteínas de Transporte de Catión/genética , Inflamación , Monocitos/metabolismo , Músculos/metabolismo , Zinc/metabolismo , Proteínas de Transporte de Catión/metabolismo , Línea Celular Tumoral , Regulación de la Expresión Génica , VIH-1 , Humanos , Metalotioneína/genética , Monocitos/virología , Músculos/virología , ARN Mensajero , Células THP-1 , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
The prevalence of iron (Fe) deficiency and subclinical lead (Pb) toxicity is high in developing countries like India, and information on their potential additive effects on immune responses is scant. The current study assessed immune parameters in dual Pb-exposed\Fe-deficient weanling SD rats. Rats were fed a control (CD) or Fe-deficient (ID) diet for 4 weeks and then evaluated for hemoglobin (Hb) and serum Fe status. Then, half the rats in each group began to receive daily oral Pb exposure (25 mg/4 ml/kg BW; gavage) or vehicle for a further 4 weeks (while maintained on original respective diets). After the 4-weeks of dosing, rats were assessed for Hb and serum Fe, and for blood lead level (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity. At this point, half the rats in each group (now n = 8) were then vaccinated with tetanus toxoid (TT), and then two boosters at 2-week intervals. All the time, rats stayed on their original respective diets along with exposure to Pb on alternate days. At 2 weeks after the final booster, rats were euthanized and blood collected to assess total/specific IgG and IgM levels; mucosal (intestinal) IgA levels were also determined. Spleens were taken to assess CD4+ and CD8+ cell levels and for ex vivo measures of splenocyte proliferation/TH1 and TH2 cytokine formation. The results indicated significant lowering of Hb and serum Fe levels in ID rats and increased blood Pb and decreased ALAD activity in all Pb-exposed rats. Fe-deficiency alone induced significant increases in ALAD activity, but only in an absence of Pb. While there was no impact of any regimen on total or TT-specific IgG, significant decreases in mucosal IgA and TT-specific IgM were seen in ID-fed Pb-exposed rats. CD4+ cell levels were not impacted by treatment; CD8+ levels were increased in all ID/Pb-exposed rats. Ex-vivo splenocyte proliferation was significantly higher among vaccinated rats, as well as ID-fed Pb-exposed unvaccinated rats. Cytokine formation in all cases was highly variable. The results suggest that Fe deficiency compromised cell-mediated, mucosal, and/or humoral immune response-related endpoints and that Pb exposure during the deficiency further impacted these outcomes.
Asunto(s)
Anemia Ferropénica/inmunología , Plomo/toxicidad , Linfocitos T/inmunología , Toxoide Tetánico/inmunología , Administración Oral , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Anemia Ferropénica/diagnóstico , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Hemoglobinas/análisis , Humanos , Inmunidad Humoral/efectos de los fármacos , Inmunidad Mucosa/efectos de los fármacos , Inmunización Secundaria , Inmunogenicidad Vacunal , Hierro/sangre , Deficiencias de Hierro , Plomo/administración & dosificación , Activación de Linfocitos/efectos de los fármacos , Masculino , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Bazo/citología , Bazo/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Toxoide Tetánico/administración & dosificación , DesteteRESUMEN
The impact of environmental pollution, especially chronic low exposures of heavy metals (Pb, Cd, Hg, As, Cr, etc.) on nutritional status and health of human and livestock, has become a cause of concern. It is established that malnutrition inhibits enzyme system, alters neurotransmitter levels, degenerate myelin, glial and neural elements, lowering of IQ scores as well as impairment of fine and gross motor coordination. Chronic low-level exposure to heavy metals also results in similar type of deformities at sub-clinical level. However, additive impact of undernutrition and adverse effects of heavy metal exposure is emerging as a serious threat to health in developing countries. High blood Pb/Cd levels and low nutrient levels cause subclinical damage of organ system such as haemopoietic, renal, nervous systems in neonates, children, post-partum women, and occupationally exposed population. This could be due to chronic low-level heavy metal exposures and vis-à-vis interaction between pollutants and nutrients. Our studies are focused on the utility of biomarkers for early subclinical detection of haemopoietic and rental toxicity. Lead exposure from non-conventional sources such as toys, pet/glass bottles, etc. suggest long-term investigation. The present review compiles result of studies conducted in this area highlighting the importance of pollution-nutrition interaction. This may facilitate policymakers on developing the strategies to counter the heavy metal exposure of humans/livestock and their consequences.
Asunto(s)
Monitoreo del Ambiente , Contaminación Ambiental/efectos adversos , Plomo/toxicidad , Estado Nutricional , Animales , Preescolar , Enfermedades Carenciales/etiología , Femenino , Humanos , India , Lactante , Recién Nacido , Plomo/sangre , Metales Pesados/toxicidad , Exposición Profesional/efectos adversos , Embarazo , InvestigaciónRESUMEN
CONTEXT: The importance of phytochemicals/natural products as potential therapeutic agents in the present context is gaining a lot of importance. India with a rich heritage of such preparations needs evaluation as potent drugs. Explant culture system is a method, which is sensitive, reliable, reproducible and is capable of mimicking the in situ conditions maintaining the tissue in sufficiently high level of integration. AIM: The current study aimed to test the antioxidant activity of test compounds, namely, traditional aqueous (4212) and aqueous-methanolic (4308) extracts of Rasna panchaka using liver explant cultures. MATERIALS AND METHODS: Dose-response optima of extracts (0.2-10 µg/mL) were determined using mouse liver explant culture system up to 48 h. The antioxidant property of extracts was assessed by primary oxidative defense parameters, namely, superoxide-dismutase (SOD), catalase, reduced glutathione (GSH), and malondialdehyde (MDA). RESULTS: The results indicated that the cellular architecture of the cultured tissue was well conserved in the first 6 h with a gradual display of specific changes in the next 24 h. There was a significant increase in MDA levels in experimental groups indicating the oxidative stress induction in explants. A dose of 2.0 µg/mL extracts have shown statistically significant (P < 0.05) protection against oxidative stress. MDA levels, a measure of lipid peroxidation, were significantly (P < 0.01) reduced by 50% in extract treated explants compared to control. This effect was accompanied by the increase in the first defense enzymes SOD (50%) and catalase (18%) with no change in reduced GSH levels. CONCLUSION: The study enforces the importance of "explant culture system," as it not only reduces the use of nonclinical/animal model but also is rapid and sensitive. Further, results of the current study also suggest that aqueous-methanolic extract of Rasna panchaka is having superior antioxidant activity compared to traditional water extract.