Monocrotophos Induces the Expression of Xenobiotic Metabolizing Cytochrome P450s (CYP2C8 and CYP3A4) and Neurotoxicity in Human Brain Cells

Tripathi, V. K.,Kumar, V.,Pandey, A.,Vatsa, P.,Dhasmana, A.,Singh, R. P.,Appikonda, S. H.,Hwang, I.,Lohani, M. Humana Press 2017 Molecular Neurobiology Vol. No.

<P>Expression of various cytochrome P450s (CYPs) in mammalian brain cells is well documented. However, such studies are hampered in neural/glial cells of human origin due to nonavailability of human brain cells. To address this issue, we investigated the expression and inducibility of CYP2C8 and CYP3A4 and their responsiveness against cyclophosphamide (CPA) and organophosphorus pesticide monocrotophos (MCP), a known developmental neurotoxicant in human neural (SH-SY5Y) and glial (U373-MG) cell lines. CPA induced significant expression of CYP2C8 and CYP3A4 in both types of cells in a time-dependent manner. Neural cell line exhibited relatively higher constitutive and inducible expression of CYPs than the glial cell line. MCP exposure alone could not induce the significant expression of CYPs, whereas the cells preexposed to CPA showed a significant response to MCP. Similar to the case of CPA induced expressions, neural cells were found to be more vulnerable than glial cells. Our data indicate differential expressions of CYPs in cultured human neural and glial cell lines. The findings were synchronized with protein ligand docking studies, which showed a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR and PXR. Similarly, the known CYP inducer CPA has also shown significant high docking scores with the two studied CYP regulators. We also observed a significant induction in reactive oxygen species (ROS), lipid peroxides (LPO), micronucleus (MN), chromosomal aberration (CA), and reduction in reduced glutathione (GSH) and catalase following the exposure of MCP. Moreover, the expressions of apoptotic markers such as caspase-3, caspase-9, Bax, and p53 were significantly upregulated, whereas the levels of antiapoptotic marker, Bcl2, was downregulated after the exposure of MCP in both cell lines. These findings confirm the involvement of ROS-mediated oxidative stress, which subsequently triggers apoptosis pathways in both human neural (SH-SY5Y) and glial (U373-MG) cell lines following the exposure of MCP.</P>

Cytotoxicity, Apoptosis Induction and Anti-Metastatic Potential of Oroxylum indicum in Human Breast Cancer Cells

Kumar, D.R. Naveen,George, V. Cijo,Suresh, P.K.,Kumar, R. Ashok Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Despite clinical advances in anticancer therapy, there is still a need for novel anticancer metabolites, with higher efficacy and lesser side effects. Oroxylum indicum (L.) Vent. is a small tree of the Bignoniaceae family which is well known for its food and medicinal properties. In present study, the chemopreventive properties of O. indicum hot and cold non-polar extracts (petroleum ether and chloroform) were investigated with MDA-MB-231 (cancer cells) and WRL-68 (non-tumor cells) by XTT assay. All the extracts, and particularly the petroleum ether hot extract (PHO), exhibited significantly (P<0.05) higher cytotoxicity in MDA-MB-231 when compared to WRL-68 cells. PHO was then tested for apoptosis induction in estrogen receptor (ER)-negative (MDA-MB-231) and ER-positive (MCF-7) breast cancer cells by cellular DNA fragmentation ELISA, where it proved more efficient in the MDA-MB-231 cells. Further, when PHO was tested for anti-metastatic potential in a cell migration inhibition assay, it exhibited beneficial effects. Thus non-polar extracts of O. indicum (especially PHO) can effectively target ER-negative breast cancer cells to induce apoptosis, without harming normal cells by cancer-specific cytotoxicity. Hence, it could be considered as an extract with candidate precursors to possibly harness or alleviate ER-negative breast cancer progression even in advanced stages of malignancy.

Serum and CSF Mineral Profile of Himalayan Yak (Bas grunniens) in their Natural Habitat

Singh, S.P.,Kumar, N.,Sharma, K.B.,Kumar, R. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.2

Mineral profile of serum and cerebrospinal fluid (CSF) of 15 Himalayan Yak (adult female, n=8; adult male n=4 and young male,n=3) was studied in their natural habitat at an altitude of 3300 meters above mean sea level at Sangla in north western Himalayas. The macro and micro minerals estimated in serum and CSF were; Sodium, Potassium, Calcium and Magnesium and Zinc, Copper and Iron respectively. The values recorded among different Yak groups did not significantly differ from each other except serum iron and haemoglobin which were significantly higher (p<0.05 ) in young male Yaks compared to the adult male and female Yaks. An observation of great significance was considerably higher potassium and lower sodium level in Yaks compared to other bovine species of plains. The serum potassium values in some adult female Yaks were recorded as high as 10.4 mEq/l and the values varied between 6.6 to 9.8 mEq/l in young male Yaks. The serum Sodium values and Na:K ratios in Yak serum ranged between 117.5 to 122.6 mEq/l and 13.7 to 15.3 respectively. The possible relationship of high serum Potassium value with hypoxic conditions and hostile mountain environment has been discussed.

Quantitative Assessment of the Relative Antineoplastic Potential of the n-butanolic Leaf Extract of Annona Muricata Linn. in Normal and immortalized Human Cell Lines

George, V. Cijo,Kumar, D.R. Naveen,Rajkumar, V.,Suresh, P.K.,Kumar, R. Ashok Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

Natural products have been the target for cancer therapy for several years but there is still a dearth of information on potent compounds that may protect normal cells and selectively destroy cancerous cells. The present study was aimed to evaluate the cytotoxic potential of n-butanolic leaf extract of $Annona$ $muricata$ L. on WRL-68 (normal human hepatic cells), MDA-MB-435S (human breast carcinoma cells) and HaCaT (human immortalized keratinocyte cells) lines by XTT assay. Prior to cytotoxicity testing, the extract was subjected to phytochemical screening for detecting the presence of compounds with therapeutic potential. Their relative antioxidant properties were evaluated using the reducing power and $DPPH^*$radical scavenging assay. Since most of the observed chemo-preventive potential invariably correlated with the amount of total phenolics present in the extract, their levels were quantified and identified by HPLC analysis. Correlation studies indicated a strong and significant (P<0.05) positive correlation of phenolic compounds with free radical scavenging potential. The results revealed that the extract was moderately cytotoxic to normal cells with a mean IC50 value of 52.4 ${\mu}g$ when compared with those obtained for cancerous cells (IC50 values of 29.2 ${\mu}g$ for MDA-MB-435S and 30.1 ${\mu}g$ for HaCaT respectively). The study confirms the presence of therapeutically active antineoplastic compounds in the n-butanolic leaf extract of $Annona$ $muricata$. Isolation of the active metabolites from the extract is in prospect.

Vitellogenin Induction and Histo-metabolic Changes Following Exposure of Cyprinus carpio to Methyl Paraben

Barse, A.V.,Chakrabarti, T.,Ghosh, T.K.,Pal, A.K.,Kumar, Neeraj,Raman, R.P.,Jadhao, S.B. Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.12

Methyl paraben (MP), which is used as a preservative in pharmaceutical and cosmetic (shampoo) products, foods and beverages, enters into the aquatic environment and can pose a potential fish health hazard. In this experiment, effects of MP were evaluated in adult male common carp (Cyprinus carpio) by exposing them to fractions (1/$143^{rd}$ to 1/29th) of the $LC_{50}$ dose with every change of water for 28 days. Vitellogenin induction, metabolic enzymes, somatic indices and bioaccumulation were studied at weekly intervals. The $96^{th}$ h $LC_{50}$ of MP in fingerlings was 120 mg/L. Compared to the control, except for increases (p<0.01) in alkaline phosphatase (EC 3.1.3.1), alanine aminotransferase (EC 2.6.1.2) and liver size, there were decreases (p<0.01) in activity of acid phosphatase (EC 3.1.3.2), aspartate aminotransferase (EC 2.6.1.1), and testiculosomatic index following exposure to any dose of MP. Vitellogenin induction was significantly higher (p<0.01) in exposed than unexposed (control) fish. The bioaccumulation of MP in testis, liver, brain, gills and muscle tissues of fish increased significantly (p<0.01) with increase of dose from 0.84 ppm to 1.68 ppm. Dose and duration of exposure (p<0.01) indicated that an exposure period of 1 to 2 weeks was sufficient to cause changes in the quantifiable parameters studied. Fish exposed to 4.2 ppm MP became lethargic after the $26^{th}$ d. Histologically, degeneration, vacuolization and focal necrotic changes in liver and fibrosis-like changes in testicular tissue were noted.

Effect of microwave processing on structural, dielectric and ferroelectric properties of calcium-doped BaTiO3 ceramics

Sonia,R.K. Patel,C. Prakash,P. Kumar 한양대학교 세라믹연구소 2011 Journal of Ceramic Processing Research Vol.12 No.6

Calcium-doped barium titanate, Ba(1−x)CaxTiO3 (where x = 0.02,0.04,0.06 & 0.08)/BCT1,BCT2, BCT3 & BCT4, ferroelectric ceramics were synthesized by a microwave processing technique. For the formation of a single perovskite phase with a dense grain morphology, microwave sintering temperature was optimized at 1100 oC for 1 h. SEM characterization of the microwave sintered BCT samples showed dense and homogeneous packing of sub-micrometer size grains. The BCT2 system showed the highest room temperature (RT) dielectric constant (εr). The dielectric property vs. temperature behavior revealed a diffuse phase transition nature. The occurrence of polarization vs. electric field (P-E) loops confirmed the ferroelectric nature of the microwave sintered BCT samples.

Effect of Graded Dietary Levels of Neem (Azadirachta indica) Seed Kernel Cake on Carcass Characteristics of Broiler Rabbits

Vasanthakumar, P.,Sharma, K.,Sastry, V.R.B.,Kumar, S. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.8

Rabbits (48) of Soviet chinchilla (24) and White giant (24) were fed from 6 weeks to 12 weeks of age intensively on either of four isonitrogenous - isocaloric diets containing 0 ($D_1$), 5($D_2$), 10($D_3$) and 20($D_4$) percent raw neem seed kernel cake (NSKC), respectively as per NRC (1977) requirements in a Randomized block design and slaughtered at the end to find out differences in their carcass traits due to NSKC feeding. Dietary treatment had no significant effect on weight of edibles and inedibles and their percentages and dressing percentage in terms of carcass, carcass with pluck and carcass with pluck and head. Similarly, the meat-bone ratio of various primal cuts and overall carcass, yield of edibles per unit of inedibles and eye muscle area were not influenced due to the dietary variations. Chemical composition of fresh meat, and organoleptic evaluation of cooked meat with and without salt did not vary significantly due to incorporation of NSKC in the diets. The rabbits fed 20% NSKC ($D_4$) though consumed more (p<0.05) DM and DE per kg meat production, the intake of crude protein and total digestible nutrients was similar with other dietary treatments. Feed cost per unit meat production was, however, lower on 5 and 10% NSKC containing diets by 7.75 and 12.56%, respectively, as compared to deoiled ground nut cake containing control diet. It appears that NSKC could be used as a wholesome vegetable protein supplement upto 10% in diet of rabbits without any adverse effect on commercial carcass traits.

Fracture energy and tension softening relation for nanomodified concrete

A. Ramachandra Murthy,P. Ganesh,S. Sundar Kumar,Nagesh R. Iyer 국제구조공학회 2015 Structural Engineering and Mechanics, An Int'l Jou Vol.54 No.6

This paper presents the details of size independent fracture energy and bi-linear tension softening relation for nano modified high strength concrete. Nano silica in powder form has been used as partial replacement of cement by 2 wt%. Two popular methods, namely, simplified boundary effect method of Karihaloo et al. (2003) and RILEM (1985) fracture energy with P-δ tail correction have been employed for estimation of size independent fracture energy for nano modified high strength concrete (compressive strength ranges from 55 MPa to 72 MPa). It is found that both the methods gave nearly same values, which is an additional evidence that either of them can be employed for determination of size independent fracture energy. Bi-linear tension softening relation corresponding to their size independent fracture energy has been constructed in an inverse manner based on the concept of non-linear hinge from the load-crack mouth opening plots of notched three-point bend beams.

Effect of aluminum doping on the structural and luminescent properties of ZnO nanoparticles synthesized by wet chemical method

Kumar, R. Saravana,Sathyamoorthy, R.,Sudhagar, P.,Matheswaran, P.,Hrudhya, C.P.,Kang, Yong Soo Elsevier 2011 Physica E, Low-dimensional systems & nanostructure Vol.43 No.6

<P><B>Abstract</B></P><P>The critical role that dopants play in semiconductor devices has stimulated research on the properties and the potential applications of semiconductor nanocrystals. Hence the investigation of the role of dopant concentration on the properties of semiconductor nanoparticles is very important from the viewpoints of basic physics as well as applications. In this context, in the present work Al-doped ZnO (AZO) nanoparticles were synthesized by simple wet chemical route. The structure and morphology of the nanoparticles analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed hexagonal wurtzite structure with flower-like clusters consisting of multi-nanorods. Energy Dispersive Spectrum (EDS) confirms the substitution of Al into ZnO lattice. Defect analysis and excitonic effect of the nanoparticles were investigated by photoluminescence (PL) and UV–Vis absorption measurements, respectively. Optical absorption showed band gap broadening due to quantum confinement effect. PL measurements exhibited both near band edge (NBE) and deep level (DL) emissions. The effect of doping concentration on the growth, crystallization and defect distribution of AZO nanoparticles was studied.</P> <P><B>Research highlights</B></P><P>► Al-doped ZnO nanoparticles were synthesized by facile wet chemical approach. ► Influence of Al doping on the physical properties of ZnO nanoparticles was investigated. ► Crystallinity of the ZnO nanoparticles deteriorated with Al incorporation. ► Broadening of the band gap due to quantum confinement effect was observed upon Al doping. ► Al doping causes annihilation of defect emission and enhancement of UV emission in ZnO.</P>

Metal oxide curcumin incorporated polymer patches for wound healing

R., Thamarai Selvi,A.P.S., Prasanna,R., Niranjan,M., Kaushik,T., Devasena,J., Kumar,Chelliah, Ramachandran,Oh, Deog-Hwan,S., Swaminathan,G., Devanand Venkatasubbu Elsevier 2018 APPLIED SURFACE SCIENCE - Vol.449 No.-

<P><B>Abstract</B></P> <P>Sodium alginate and Poly vinyl alcohol (PVA) based scaffolds are very well used for wound healing purpose. Sodium alginate is a natural polymer which is used for many biomedical applications. PVA is a biocompatible polymer used in many biomedical applications. Incorporation of Titanium dioxide (TiO<SUB>2</SUB>) nanoparticles in the scaffold increases the wound healing property of the scaffold. TiO<SUB>2</SUB> nanoparticles are biocompatible. They enhance the wound healing activity by photo catalytic property. Curcumin is used for the treatment of inflammation. It is the main active compound of turmeric Curcumin is used for treatment of wound and inflammation. It had antimicrobial and antioxidant property.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The work deals with the fabrication of patches for wound healing. </LI> <LI> Matal oxide nanoparticle is incorporated in the patch. </LI> <LI> Curcumin is incorporated in the patch. </LI> <LI> The patch surface is used for wound healing. </LI> <LI> Antibacterial and antifungal studies are done. </LI> </UL> </P>