Mahuya Sengupta

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice.

OBJECTIVE To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice. METHODS First group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups. RESULTS The result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice. CONCLUSIONS In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

Lead toxicity on non-specific immune mechanisms of freshwater fish Channa punctatus

Lead has no known role in the body that is physiologically relevant, and its harmful effects are myriad. Lead from the atmosphere and soil ends up in water bodies thus affecting the aquatic organisms. This situation has thus prompted numerous investigations on the effects of this metal on the biological functions of aquatic organisms, particularly on immune mechanisms in fish. This paper addresses the immunotoxicologic effects of lead acetate in intestinal macrophages of freshwater fish Channa punctatus. Fish were exposed to lead acetate (9.43mg/l) for 4 days. When checked for its effects on macrophages, it was noted that lead interfered with bacterial phagocytosis, intracellular killing capacity and cell adhesion as well as inhibited release of antimicrobial substances like nitric oxide (NO) and myeloperoxidase (MPO). On giving bacterial challenge with Staphylococcus aureus to intestinal macrophages of both control and lead treated groups, the macrophages showed significantly higher concentration of viable bacteria in the intracellular milieu in lead treated group as compared to control. We also report that in vivo exposure to lead acetate inhibits phagocytosis, which is evident from a reduced phagocytic index of treated group from that of the control. The amount of MPO and NO released by the control cells was also reduced significantly upon in vivo lead treatment. The property of antigenic adherence to the macrophage cell membrane, a vital process in phagocytosis, was significantly decreased in the treated group as compared to control. Severe damage in intestinal epithelium, disarrangement and fragmentation of mucosal foldings was observed in lead treated group when compared with the untreated group. The present results also showed decreased tumor necrosis factor-alpha (TNF-α) level upon metal exposure in sera as well as cell lysate of lead exposed fish thus, implicating both MAPK signaling pathways as well as NFκβ signaling. We thus conclude that lead affects the general immune status of C. punctatus and renders the fish immunocompromised and susceptible to pathogens.

Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

BackgroundThe current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of Tinospora cordifolia extract that are exerted on circulating macrophages isolated from CCl4 (0.5 ml/kg body weight) intoxicated male albino mice.MethodsApart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO), nitric oxide (NO) release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. T. cordifolia extract was tested for acute toxicity at the given dose (150 mg/kg body weight) by lactate dehydrogenase (LDH) assay.ResultsThe number of morphologically altered macrophages was increased in mice exposed to CCl4. Administration of CCl4 (i.p.) also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl4 intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl4. However oral administration of aqueous fraction of Tinospora cordifolia stem parts at a dose of 40 mg/kg body weight (in vivo) in CCl4 exposed mice ameliorated the effect of CCl4, as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl4 intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous extract of Tinospora cordifolia at a dose of 150 mg/kg body weight.ConclusionFrom our findings it can be suggested that, polar fractions of Tinospora cordifolia stem parts contain major bioactive compounds, which directly act on peritoneal macrophages and have been found to boost the non-specific host defenses of the immune system. However, the molecular mechanism of this activity of Tinospora cordifolia on immune functions needs to be elucidated.

Noble metal nanoparticle-induced oxidative stress modulates tumor associated macrophages (TAMs) from an M2 to M1 phenotype: An in vitro approach.

Diagnosis of cancer and photothermal therapy using optoelectronic properties of noble metal nanoparticles (NPs) has established a new therapeutic approach for treating cancer. Here we address the intrinsic properties of noble metal NPs (gold and silver) as well as the mechanism of their potential antitumor activity. For this, the study addresses the functional characterization of tumor associated macrophages (TAMs) isolated from murine fibrosarcoma induced by a chemical carcinogen, 3-methylcholanthrene (MCA). We have previously shown antitumor activity of both gold nanoparticles (AuNPs) and silver nanoparticle (AgNPs) in vivo in a murine fibrosarcoma model. In the present study, it has been seen that AuNPs and AgNPs modulate the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, suppressing the antioxidant system of cells (TAMs). Moreover, the antioxidant-mimetic action of these NPs maintain the ROS and RNS levels in TAMs which act as second messengers to activate the proinflammatory signaling cascades. Thus, while there is a downregulation of tumor necrosis factor-α (TNF-α) and Interleukin-10 (IL-10) in the TAMs, the proinflammatory cytokine Interleukin-12 (IL-12) is upregulated resulting in a polarization of TAMs from M2 (anti-inflammatory) to M1 (pro-inflammatory) nature.

Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma

The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles (AgNPs) have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses (1–10 mg/kg b.w.) were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1β were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA.

Synthesis, electrochemical and antimicrobial studies of mono and binuclear iron(III) and oxovanadium(IV) complexes of [ONO] donor tridentate Schiff-base ligands

Tridentate Schiff bases (H2L1 or H2L2) were derived from condensation of acetylacetone and 2-aminophenol or 2-aminobenzoic acid. Binuclear square pyramidal complexes of the type [M2(L1)2] · nH2O (M = Fe–Cl, n = 0; M = VO, n = 1) were accessed from interaction of H2L1 with anhydrous FeCl3 and VOSO4 · 5H2O, respectively. A similar reaction with H2L2, however, produced mononuclear complexes [ML2(H2O) x ] · nH2O (M=Fe–Cl, x = 0, n = 0; M=VO, x = 1, n = 1). The compounds were characterized using elemental analysis, FT-IR, UV-Vis, and NMR (for ligand only), and mass spectroscopies and solution electrical conductivity studies. Magnetic susceptibility measurements suggest antiferromagnetic exchange in binuclear Fe(III) and VO(IV) complexes. Thermo gravimetric analysis (TGA) provided unambiguous evidence for the presence of coordinated as well as lattice water in [VOL2(H2O)] · H2O. Cyclic voltammetric studies showed well-defined redox processes corresponding to Fe(III)/Fe(II) and VO(V)/VO(IV). In vitro antimicrobial activities of the compounds were investigated against Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeroginosa, Escherichia coli, Bacillus subtilis, and Proteus vulgaris. H2L1 and its binuclear complexes exhibited pronounced activity against all the microorganisms tested.

Novel water soluble neutral vanadium(IV)–antibiotic complex: Antioxidant, immunomodulatory and molecular docking studies

A novel water soluble five coordinate oxovanadium(IV) complex, [VO(C16H15N4O8S)HSO4] incorporating cefuroxime, a cephalosporin group of antibiotic have been prepared from an interaction of vanadyl sulfate and cefuroxime in aqueous solution. The compound was characterized by Fourier transform infrared spectroscopy (FTIR), CHN microanalyses, ultraviolet-visible spectroscopy (UV-Vis), fast atom bombardment (FAB) mass spectrometry and thermogravimetric analysis (TGA). Density Functional Theory (DFT) computation using Gaussian 09 program at B3LYP level revealed a distorted square pyramidal energy optimized geometry for the vanadyl(IV) complex. The molecular docking studies show that the interaction between the vanadium complex and protein receptor, clathrin is dominated by hydrophobic forces. The experimental (1)H nuclear magnetic resonance (NMR) features of the analogous Zn(II) complex matched well with the theoretically computed values further affirming the distorted square pyramidal geometry for the vanadyl(IV) complex. Cyclic voltammetry revealed a metal centered single-electron oxidation-reduction response for VO(IV)/VO(V) couple. The antioxidant activity of the vanadium(IV)-complex vis-à-vis the antibiotic has been assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The vanadium complex showed comparatively better radical scavenging ability compared to the antibiotic cefuroxime. The antimicrobial activity of the compound has been assayed for five different microbial strains using minimum inhibitory concentration (MIC) method. Immunomodulatory studies carried out using phagocytosis index, myeloperoxidase release and cytokine assay indicated the vanadium(IV)-complex to be immunosuppressant. The cytotoxicity of the compound was evaluated by MTT (3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) reduction assay.

Bactericidal activity of selected medicinal plants against multidrug resistant bacterial strains from clinical isolates

OBJECTIVE To investigate the antibacterial effect of Curcuma longa (C. longa), Zingiber officinale (Z. officinale) and Tinospora cordifolia (T. cordifolia) against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Bacillus subtilis and Proteus mirabilis of clinical origin. METHODS The antimicrobial efficacy of said medicinal plants and establishment of multidrug resistant character of these bacteria were carried out using disc diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. RESULTS The results of MIC and MBC showed that these clinical bacterial isolates were phenotypically multidrug resistant against standard antibiotics (>500 μg/mL). Compared to standard antibiotics, C. longa, Z. officinale and T. cordifolia were more effective in killing these microbes as evident from MIC and MBC values (5 to 125 μg/mL). Moreover, C. longa had highest antibacterial efficacy compared to Z. officinale and T. cordifolia. CONCLUSIONS The result thus obtained suggests that bioactive principles of these plants can be used particularly against these multidrug resistant bacteria of clinical origin.

Human sperm and other seminal constituents in male infertile patients from arsenic and cadmium rich areas of Southern Assam

In the present study the occurrence of two heavy metals, arsenic and cadmium, have been reported in the drinking water and seminal plasma of infertile male patients as compared to a control group. The study originated from a survey of geogenic groundwater contamination with the heavy metals arsenic and cadmium in Southern Assam, India as an increase in the incidence of male infertility was being reported from these areas. According to WHO protocol, patients with sperm concentration < 20x106/ml were selected as cases (oligozoospermic and azoospermic), and those with > 20x106/ml, without any extreme pathological disorders and having fathered a child within 1-2 years of marriage were the control (normozoospermic) group. The study reports an inverse relationship between total sperm count and heavy metal content in drinking water as well as seminal plasma of the subjects. Moreover, a high correlation between altered semenological parameters and lower expression of accessory sex gland markers like fructose, acid phosphatase, and neutral α-glucosidase in the seminal plasma of patients is reported. The study also highlights significant differences of the sperm function parameters like hypo-osmotic swelling, acrosome reaction, and nuclear chromatin decondensation in the patient group as compared to controls. These findings are significant as they address a likely association between heavy metal stress and altered sperm function as well as seminal enzyme inhibition.

Immunomodulation of intestinal macrophages by mercury involves oxidative damage and rise of pro-inflammatory cytokine release in the fresh water fish Channa punctatus Bloch.

Mercury and its compounds have been parts of widespread pollutants of the aquatic environment. The present study was designed to assess the effect of mercury on fish immune responses. Since the metal is absorbed by fish and passed up the food chain to other fish-eating species, it not only affects aquatic ecosystems but also humans through bioaccumulation. In the present study, it was found that innate immunity of the fresh water fish Channa punctatus Bloch. was significantly debilitated after a periods of exposure to a sub-lethal concentration of mercury (0.3 mg/L). After 7 days of exposure, phagocytosis, cell adhesion and intracellular killing activity were found to decrease significantly along with significant decreases in nitric oxide (NO) and myeloperoxidase (MPO) production from macrophages as compared to the control group indicating intracellular damages. Levels of pro-inflammatory cytokines like TNF-α and IL-6 were found to be significantly more in mercury treated groups than that of control group indicating inflammatory damage. This included significant ultrastructural changes like fragmented epithelium, lesions in mucosal foldings, degenerated mitochondria, reduction in the number of goblet cells and disoriented microvilli as evident from transmission electron micrographs.