No abstract

Curcumin (diferuloylmethane), a natural cancer chemopreventive compound, has been tested for its action in acute myeloblastic leukemia cell line HL-60. The results clearly show that curcumin induces apoptosis in these cells as evidenced by the release of cytochrome c from mitochondria to the cytosol and increase in the DNA content in sub G1 region as observed in FACS analysis. Apoptosis is apparently mediated by up-regulation of apoptotic gene bax and simultaneous down-regulation of anti-apoptotic gene bcl-2 followed by activation of caspases 3 and 8 and degradation of PARP. Telomerase, a reverse transcriptase, has been found to be activated in more than 80% of human cancers and, therefore, can be considered as a potential marker for tumorigenesis. Certain natural compounds have the potential of inhibiting telomerase activity leading to suppression of cell viability and induction of apoptosis. The present study shows that curcumin-induced apoptosis coincides with the inhibition of telomerase activity in a dose dependent manner.

Objective: To study the effect of α−cypermethrin (α−CP) on some neuropharmacological paradigms like motor coordination, pentobarbitone-induced sleeping time and pentylenetetrazole-induced (PTZ) convulsion as well as γ-aminobutyric acid (GABA) level in rat brain. Materials and Methods: Albino Wistar rats were the experimental animals. Different neuropharmacological paradigms like motor coordination (determined by rotarod), pentobarbitone-induced sleeping time and PTZ-induced convulsion were carried out following oral administration of α−CP at two dose levels i.e., 145 mg/kg (LD 50) and 14.5 mg/kg (1/10LD 50), while the level of GABA in the brain of rats was estimated by HPLC after single-dose oral administration of α−CP at 145 mg/kg. Results: α−CP induced significant motor incoordination, decreased the time of onset and increased the duration of sleeping time induced by pentobarbitone; and also decreased the time of onset and increased the duration of convulsion induced by PTZ at the dose levels of 145 mg/kg (LD 50) and 14.5 mg/kg (1/10 LD 50) respectively. Further α−CP decreased brain GABA levels in the cerebellum and in whole brain (except cerebellum) significantly at LD 50 dose level. Conclusion: A correlation between the effect of α−CP on central GABA levels and its neuropharmacological effects can be hypothesized.

This study examined the effect of deltamethrin on some of the neuropharmacological paradigms in a rat brain such as the motor co-ordination test using a rotarod, the pentobarbitone-induced sleeping time and pentylenetetrazole (PTZ)-induced convulsion as well as the gamma aminobutyric acid (GABA) level. Albino Wistar rats were used as the experimental animals. Different neuropharmacological paradigms such as the motor co-ordination by the rotarod, pentobarbitone-induced sleeping time and the PTZ-induced convulsion were examined after administering deltamethrin orally at two doses, 150 mg/kg (LD50) and 15 mg/kg (1/10 LD50). The GABA level in the rat brain was estimated by HPLC after a single oral dose of 150mg/kg deltamethrin. Deltamethrin significantly reduced the motor coordination, decreased the onset time and increased the sleeping time duration induced by pentobarbitone. In addition, it also decreased the onset time and increased the duration of convulsions induced by PTZ at 150 mg/kg (LD50) and 15 mg/kg (1/10 LD50), respectively. Further deltamethrin administration decreased the GABA levels in the cerebellum as well as in the whole brain (except the cerebellum) significantly at the LD50 dose level. There was some correlation between the effect of deltamethrin on the central GABA levels and its neuropharmacological effects.

Summary Chronic exposure of humans to high concentrations of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, blackfoot disease and a high risk of cancer. Arsenic induces single strand breaks, DNA-protein crosslinks and apurinic sites in DNA, which are prerequisites for induction of cancer. Amelioration of such damages with natural compounds could be an effective strategy to combat arsenic toxicity. Curcumin is the active ingredient of turmeric, a common household spice, which is a rich source of polyphenols and this compound has been extensively studied as a chemopreventive agent against many types of cancer. The present study investigates whether curcumin could counteract the DNA damage caused by arsenic as assessed by single cell gel electrophoresis (SCGE) using peripheral blood lymphocytes, from healthy donors. It was observed that DNA damage induced by arsenic could be efficiently reduced by curcumin and the effect was more pronounced when lymphocytes were pre-incubated with curcumin prior to arsenic insult. Arsenic caused DNA damage by generation of reactive oxygen species (ROS) and enhancement of lipid peroxidation levels. Curcumin counteracted the damage by quenching ROS, decreasing the level of lipid peroxidation and increasing the level of phase II detoxification enzymes like catalase, superoxide dismutase and glutathione peroxidase. Curcumin also enhanced the DNA repair activity against arsenic induced damage. The expression of polymerase, a repair enzyme, was found to be highly elevated when arsenite induced damaged cells were allowed to repair in presence of curcumin. Results indicate that curcumin has significant role in confronting the deleterious effect caused by arsenic, which could be an economic mode of arsenic mitigation among rural population in West Bengal, India.