Antony Gomes's research while affiliated with University of Calcutta and other places

In this study, silver nanoparticles (PE-AgNPs) were synthesized using Premna esculenta (PE) leaf extract, characterized by UV, TEM, TEM-EDX, XRD, DLS, and ICPOES studies. AgNPs were found to be stable at −35 mV with 26.157 ppm concentration. AgNPs were found triangular in shape with an average size of about 44 nm. Hepatoprotective activity was assessed in animal model using silymarin as standard drug. Biochemical parameters (serum AST, ALT, γGT, ACP, and ALP), inflammatory markers (IL 1β, IL 17, TNF α, and IL 10), and antioxidant markers (GSH, SOD, Catalase, and LPO) were assayed. Liver tissue was processed for histological analysis. Induction of hepatotoxicity increases AST, ALT, γGT, ACP, ALP, IL 10, LPO, and decreases IL 1β, IL 17, TNF α, GSH, SOD, and Catalase. PE-AgNPs treatment significantly decreases IL 10, LPO while IL 1β, IL 17, TNF α, GSH, and SOD were increased in animals. PE-AgNPs partially recovered CCl4-induced changes in liver histology.

Andrographolide, a diterpenoid compound found in the aerial parts of Andrographis paniculata (a well known anti snake venom plant) was conjugated with gold nanoparticle (andrographolide-AuNPs) and its efficacy against Daboia russellii russellii venom (DRRV) induced local damage, organ toxicity and inflammatory response was evaluated in animal models. Ethical clearance was obtained before animal experiments. Andrographolide-AuNPs was formed by adsorption method. Physico-chemical characterization of particle was done by dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Swiss albino male mice were divided into 5 groups: Gr. 1-Sham control, Gr. 2-DRRV control, Gr. 3-anti snake venom serum treated, Gr. 4-andrographolide treated and Gr. 4-andrographolide-AuNPs treated. 1/5th minimum lethal dose of DRRV (10 μg/s.c./20 g mice) was induced in animals of group 2, 3, 4 and 5 animals, followed by treatment with anti snake venom serum (2 mg/20 g mice, i.v.) andrographolide (50 μg/20g mice, i.p.) and andrographolide-AuNPs (50 μg/20 g mice, i.v.) in group 3, 4 and 5 animals, respectively. Blood was collected after 18 h, serum was prepared and organ toxicity markers (transaminases, phosphatases, lactate dehydrogenase, creatine phosphate, urea, creatinine, Ca2+, phosphorous), inflammatory markers (interleukin 1β, 6, 17a, 10, tumor necrosis factor α) and local damage testings (defibrination, edema, hemorrhage) were assessed. Values were expressed as mean ± SEM (n = 4), one way analysis of variance was done, P < 0.05 was considered as statistically significant. Formed andrographolide-AuNPs were pink in color with hydrodynamic diameter 30-50 nm, polydispersity index 0.412 and zeta potential -16.21 mV. XRD data confirmed the presence of crystalline gold in andrographolide-AuNPs. TEM (20-50 nm) and FE-SEM (20-25 nm) indicated the presence of nearly spherical particle. DRRV envenomation followed by treatment with andrographolide-AuNPs provided protection against venom induced edema, hemorrhage, defibrination, organ toxicity and inflammation in animal model. Venom neutralization by andrographolide-AuNPs was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation, may be due to anti-oxidant/anti-inflammatory activity of andrographolide, showing increased efficacy after gold nanoparticle tagging. Thus, andrographolide-AuNPs may serve as a supportive therapy in snakebite (against venom induced local damage, organ toxicity and inflammatory response) subject to further detail studies.

Indian toad (Bufo melanostictus) skin extract (TSE) was evaluated for cytotoxic and apoptogenic activities on Ehrlich ascites carcinoma (EAC) cells of EAC bearing Swiss albino male mice. LD50 of TSE was found to be 400 mg kg-1, (i.v.) and 750 mg kg-1, (i.p.) in mice. EAC cells (1-2  105 / mouse) were inoculated (i.p.) into mice (20.6  0.14 gm) and the status of EAC cell proliferation and viability were studied in control and TSE treated groups. TSE (10, 20, 30 mg kg-1 d-1, i.p. for 10 d) significantly inhibit EAC cell growth in dose dependent manner. TSE (50, 100 mg kg-1 d-1, i.p. for 1 d) significantly reduced the viability of EAC cells and decreased the MTT values compared to control cells. TSE induced DNA breakage was reflected in DNA ladder and single cell gel electrophoresis (comet assay). TSE significantly (P<0.001) increased the number tailed cells and length-width ratio of DNA mass in EAC cells as compared to control. Fluorescent microscopy of TSE treated cells showed significant increase in number of early and late apoptotic cells compared to the control EAC cells. Apoptotic index of TSE treated cells was significantly (P<0.001) higher than that of the control cells. Changes in serum LDH, β2-microglobulin in TSE treated EAC mice and our earlier studies indicated the involvement of immunomodulation which may indirectly be associated with the anticancer activity of TSE.

Background Tea (Camellia sinensis) being the most widely drank beverage and despite having numerous beneficial role toward health and disease, its safety evaluation during pregnancy and prenatal, postnatal developmental period need to be monitored. Objective This study was to evaluate the toxicity of black tea extract (BTE) in experimental pregnant rats and on their pups during prenatal and postnatal developmental periods. Materials and Methods Pregnant female (120 ± 10 g) Wister albino rats were chosen for this study. Group 1 was control group where pregnant female rats were treated with saline. Group 2 and Group 3 were pregnant female rats treated with 50 mg and 100 mg BTE/kg/day, respectively, throughout prenatal and postnatal periods. All three groups of rats were provided food and drinking water ad libitum. Animals were examined through their urinary and serum parameters, histopathological studies, and biomorphometric studies in pups. All data were expressed as mean ± standard deviation with significance between the controls and the treated groups (n = 6). Collected data were subjected to the analysis of variance and Tukey test; P < 0.05 was considered as statistically significant. Results BTE produced significant alterations in urinary calcium, creatinine, and urea during prenatal period; exhibited proteinuria, ketonuria, and histology showed nephrotoxicity during postnatal period, and BTE also showed a significant increase in serum proinflammatory cytokines and decreased anti-inflammatory cytokines level compared to control group. BTE caused significant changes in biomorphometric parameters in the pups as compared with pups of control mothers. Conclusion This study confirmed the BTE-induced toxicity in pregnant rats and their pups. SUMMARY Black tea (Camellia sinensis) is the most widely drank beverage. This study was to evaluate the toxicity BTE in experimental pregnant rats and on their pups during prenatal and postnatal developmental periods. Animals were examined through their urinary and serum parameters, histopathological studies, and biomorphometric studies in pups. BTE.induced toxicity in pregnant rats and their pups. Abbreviations used: BTE: Black tea extract, IL-1α: Interleukin 1 alpha, IL-1 β: Interleukin 1 beta, IL-6: Interleukin 6, IL-10: Interleukin 10, TNF-α: Tumor necrosis factor alpha.

This study was to evaluate the changes in blood and liver parameters caused by oral dose of black tea extract (BTE) in experimental albino rats throughout pregnancy and lactation periods. Pregnant female Wister albino rats were chosen for this study. Group 1 was control group treated with saline. Group 2 and Group 3 were pregnant female rats treated with 50 and 100 mg BTE/kg/day respectively throughout pregnancy and lactation periods. All three groups of rats were provided with food and drinking water ad libitum. Animals were examined through their hematological profile, SEM of RBC and liver function test. BTE (100 mg/kg/day) produced significant alterations in hemoglobin concentration, total RBC and WBC count compared to control groups. BTE (100 mg/kg/day) also induced significant changes in the histology of liver and serum enzymes for liver function test compared to control groups. This study confirmed that BTE altered the parameters of blood and liver in pregnant and lactating experimental albino rats.

Background & objectives: Increased severity of osteoarthritis (OA) and adverse side effects of its treatment led to the search for alternative therapies. It was previously reported that snake venom protein toxin Naja kaouthia cytotoxin 1 (NKCT1) and gold nanoparticle (GNP) individually have potential against excremental arthritis. In this study, we analyzed the protective activity of GNP conjugated protein toxin NKCT1 (GNP-NKCT1) against experimental OA. Methods: Gold nanoparticle conjugation with NKCT1 (GNP-NKCT1) was done and its physiochemical properties were studied. OA was induced in male albino rats by intra-articular injection of bacterial collagenase and treatment was done with NKCT1/GNP-NKCT1/standard drug (indomethacin). Physical parameter (ankle diameter), urinary markers (hydroxyproline, glucosamine, pyridinoline, deoxypyridinoline), serum and synovial membrane pro-inflammatory markers [tumour necrosis factoralpha (TNF-α), interleukin-1β (IL-1β), IL-17, vascular endothelial growth factor (VEGF)] and matrix metalloproteinase 1 (MMP1) were measured. Joint histopathology and scanning electron microscopy imaging of articular cartilage surface were also done. Results: Physical parameters, urinary markers, serum and synovial membrane pro-inflammatory makers and MMP1 were increased in arthritic rats and significantly restored after GNP-NKCT1/ NKCT1 treatment. Joint histopathology and scanning electron microscopy imaging of articular cartilage surface also indicated the protective effect of GNP-NKCT1 against inflammatory response and cartilage degradation in osteoarthritic rats. Interpretation & conclusions: In this study restoration of the arthritic markers and bone degradation by GNP-NKCT1 treatment indicated the anti-osteoarthritic property of GNP-NKCT1. Further studies need to be done to confirm these findings.

Aim: The aim of this study was to determine whether gold nanoparticles conjugated cytotoxic protein NKCT1 (GNP-NKCT1) acted through the estrogen receptor mediated pathway in MCF-7 cells and to establish the MAPK and PI3k/Akt signal transduction pathway. Methods: Apoptosis was done by flow cytometry. BrdU incorporation and nuclear proliferating antigen was measured by flow cytometry. Wound healing assay along with matrigel chamber invasion and migration was done. Expression of MMP9 was checked by flow cytometry and also by gelatin zymography. To analyze the regulation of signalling protein, western blot was done. MTT assay was done to evaluate the ligand receptor pathway using the estrogen receptor negative cell line (MDA-MB-231) for inhibitor effects. Results: Treatment of GNP-NKCT1 (3.9 μg/ml) exhibited 38.04% early apoptosis and 4.29% late apoptotic cell. GNP-NKCT1 significantly inhibited both cell migration and invasion with suppressed expression of MMP9. In addition, treatment of cultured human breast cancer MCF7 cells with GNP-NKCT1 reversely suppressed the incorporation of BrdU, with reduced expression of Ki-67. The western blot analysis showed that GNP-NKCT1 arrested cell cycle progression through upregulation of the kinase inhibitor protein p21 and inactivation of G1-cylin dependent kinase (CDK4). GNP-NKCT1 suppressed nuclear translocation of nuclear factor kappa B (NF-κB) and also abrogated the phosphorylation of p38 mitogen activated protein kinase (MAPK), phosphatidylinositide-3-kinase (PI3k), Akt and extracellular regulated kinase (ERK1/2). MTT assay indicated that GNP-NKCT1 reduced proliferation in the estrogen receptor induced ER negative breast cancer cell line (MDA-MB-231). Addition of, ER inhibitor (tamoxifen) and PI3K inhibitor (wortmannin) to cells resulted in reduced expression of Ki-67 and MMP-9. Conclusion: The data suggested that GNP-NKCT1 induced MCF7 cell inhibition may occur through estrogen receptor pathway via inactivation of CDK4 and inactivation of PI3K/Akt, ERK1/2 and p38 MAPK signalling pathway with inhibitory effects on NF-κB, reducing the activity of MMP9. This result provides a new mechanism to explain the role of gold nanoparticles conjugated NKCT1 as a potent anti-metastatic agent in MCF7 cells.