Nano Zinc Supplementation Affects Immunity, Hormonal Profile, Hepatic Superoxide Dismutase 1 (SOD1) Gene Expression and Vital Organ Histology in Wister Albino Rats.

The study was conducted to assess nano zinc (ZnN) as a feed supplement with an aim to compare the supplemental dose of inorganic zinc (ZnI). ZnN was synthesized from 0.45 molar (M) zinc nitrate [Zn(NO3)2.6H2O] and 0.9 M sodium hydroxide (NaOH) and was confirmed to be of ZnN by TEM-EDAX measurements. Wister albino rats (rats; 84, 53.6 ± 0.65 g) were divided into seven groups (4 replicate with 3 rats each) and given feed supplemented with zinc for 60 days with either of the following diets: (1) normal control (NC): basal diet (BD) + no supplemental Zn; (2) ZnI-25: BD + 25 mg/kg Zn from inorganic ZnO; (3) ZnN-25: BD + 25 mg/kg of ZnN; (4) ZnN-12.5: BD + 12.5 mg/kg of ZnN; (5) ZnN-6.25: BD + 6.25 mg/kg of ZnN; (6) ZnN-3.125: BD + 3.125 mg/kg of ZnN; (7) ZnN-50: BD + 50 mg/kg of ZnN. T3 and insulin-like growth factor-1 (IGF-1) hormone levels were similar among groups (P > 0.05), whereas T4 and testosterone were significantly affected, based on supplemented dose. Zn supplementation improved both cell-mediated and humoral immunity. However, both cell-mediated immunity at 24 h and humoral immunity were statistically similar in ZnI-25 and ZnN-6.25 groups. Superoxide dismutase 1 gene expression was found to be similar in all experimental groups. The vascular degeneration were found in liver tissues moderately in NC, mildly in ZnN-6.25 and ZnN-3.125 groups, and no observable changes were noticed in kidney and spleen tissues. However, there was a mild damage in intestinal epithelium of ZnN-25 group rats, hyperplasia of goblet cells, and moderate damage in intestinal villi were observed in ZnN-50 group rats. From the study, it can be concluded that ZnN at half the dose of ZnI showed similar or better responses in terms of immunity, SOD-1 expression, hormonal profiles, and the tissue architecture of vital organs in rats, i.e., 25 mg/kg of Zn from ZnI and 12.5 mg/kg of ZnN impacted similar biological responses like immunity, SOD-1 expression, hormonal profiles, and the tissue architecture of vital organs in rats.

New insight into organic anion transporters from the perspective of potentially important interactions and drugs toxicity.

The family of organic anion transporters (OATs) includes a group of over 10 transmembrane transporting proteins belonging to the solute carrier 22 subfamilies of the major facilitator superfamily. Their function is related to the transport of a great variety of organic anions against the electrical and chemical gradient. OATs are present in most types of human tissues, including the kidneys, liver, placenta, olfactory epithelium, retina, and choroid plexus tissues. The OATs family plays an important role in the cellular uptake, distribution, excretion, and detoxification of many water-soluble drugs, endogenous compounds, nutrition ingredients, environmental contaminants and toxins, and significantly impacts their efficacy, pharmacokinetics and toxicity, both in a preferable and unfavorable way. OATs demonstrated great potential to participate in many potentially relevant interactions, which may lead to unexpected, but not always detrimental, effects. Wider knowledge about their specific functions in the body, role in disease states, pharmacokinetics interactions, and intraindividual response to therapeutic treatment will allow to predict and prevent OAT-related adverse effects or use favorable interactions in pharmacotherapy, as well as to rationally design therapeutics targeted at individual transporter drugs with improved bioavailability, prolonged half-life or reduced toxicity, and improve safety guidelines concerning drug dosage. This review gathers recent reports regarding OAT-related essential interactions involving components of popular therapeutic herbal products, dietary supplements, and clinically important drugs, their significance and potential suitability in modulating the severity of drug-related side effects and toxicity mechanisms.

Boron influences immune and antioxidant responses by modulating hepatic superoxide dismutase activity under calcium deficit abiotic stress in Wistar rats.

The influence of Boron (B) supplementation on immune and antioxidant status of rats with or without abiotic stress induced by dietary calcium (Ca) restriction was studied in a feeding trial of 90 days. Wistar strain rats (3-4 wk age, n=84) were divided into 7 dietary groups (4 replicates of 3 each) viz., normal-calcium (100%) basal diet alone (NC, control) or supplemented with B at 5 (NCB-5), 10 (NCB-10), 20 (NCB-20) and 40ppm (NCB-40) levels; low-calcium (50%) basal diet alone (LC) or supplemented with 40ppm B (LCB-40). After 75 days of experimental feeding, rats were challenged with intraperitoneal injection of sheep RBCs to assess their humoral immunity. At the end of the trial, cell-mediated immunity was assessed as foot pad reaction to sheep RBCs injected into the hind leg paws. Eight rats from each group were sacrificed to collect blood for estimation of minerals and total antioxidant activity, and liver for superoxide dismutase gene expression analysis. Supplementation of graded levels of B (5, 10, 20 and 40ppm) as borax in NC diets significantly increased (P<0.01) the footpad thickness and serum total antioxidant activity, hepatic expression levels of both Cu-Zn SOD (SOD1) and Mn-SOD (SOD2) mRNAs. The erythrocytic SOD activity and humoral response did not differ significantly among the dietary groups. In Ca restricted groups, humoral immune response was significantly decreased (P<0.01) compared to control but increased (P<0.05) with 40ppm B supplementation. Serum levels of copper (Cu) and zinc (Zn) remained similar among the dietary groups, while the manganese (Mn) content was significantly decreased (P<0.01) with increased levels of dietary B. In conclusion, B supplementation increased the hepatic mRNA expression levels of both SOD isoenzymes, thereby improving the immune and antioxidant status.

Antimalarial activities of dermaseptin S4 derivatives.

The hemolytic antimicrobial peptide dermaseptin S4 was recently shown to exert antimalarial activity. In this study, we attempted to understand the underlying mechanism(s) and identify derivatives with improved antimalarial activity. A number of dermaseptin S4 derivatives inhibited parasite growth with a 50% inhibitory concentration (IC(50)) in the micromolar range. Among these, the substituted S4 analog K(4)K(20)-S4 was the most potent (IC(50) = 0.2 microM), while its shorter version, K(4)-S4(1-13)a, retained a considerable potency (IC(50) = 6 microM). Both K(4)K(20)-S4 and K(4)-S4(1-13)a inhibited growth of the parasites more at the trophozoite stage than at the ring stage. Significant growth inhibition was observed after as little as 1 min of exposure to peptides and proceeded with nearly linear kinetics. The peptides selectively lysed infected red blood cells (RBC) while having a weaker effect on noninfected RBC. Thus, K(4)K(20)-S4 lysed trophozoites at concentrations similar to those that inhibited their proliferation, but trophozoites were >30-fold more susceptible than normal RBC to the lytic effect of K(4)K(20)-S4, the most hemolytic dermaseptin. The same trend was observed with K(4)-S4(1-13)a. The D isomers of K(4)K(20)-S4 or K(4)-S4(1-13)a were as active as the L counterparts, indicating that antimalarial activity of these peptides, like their membrane-lytic activity, is not mediated by specific interactions with a chiral center. Moreover, dissipation of transmembrane potential experiments with infected cells indicated that the peptides induce damage in the parasite's plasma membrane. Fluorescence confocal microscopy analysis of treated infected cells also indicated that the peptide is able to find its way through the complex series of membranes and interact directly with the intracellular parasite. Overall, the data showed that dermaseptins exert antimalarial activity by lysis of infected cells. Dermaseptin derivatives are also able to disrupt the parasite plasma membrane without harming that of the host RBC.