Protective Effect of Kaempferol on the Transgenic Drosophila Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by the accumulation and deposition of ß-amyloid peptides leading to a progressive neuronal damage and cell loss. Besides several hypotheses for explaining the neurodegenerative mechanisms, oxidative stress has been considered to be one of them. Till date, there is no cure for AD, but the pathogenesis of the disease could be delayed by the use of natural antioxidants. In this context, we decided to study the effect of kaempferol against the transgenic Drosophila expressing human amyloid beta-42. METHOD: The AD flies were allowed to feed on the diet having 10, 20, 30 and 40µM of kaempferol for 30 days. After 30 days of exposure, the amyloid beta flies were studied for their climbing ability and Aversive Phototaxis Suppression assay. Amyloid beta flies head homogenate was prepared for estimating the oxidative stress markers, Caspase and acetylcholinesterase activity. RESULTS: The results of the present study reveal that the exposure of AD flies to kaempferol delayed the loss of climbing ability, memory, reduced the oxidative stress and acetylcholinesterase activity. CONCLUSION: Kaempferol could be used as a possible therapeutic agent against the progression of the Alzheimer's disease.

Toxic potential of copper-doped ZnO nanoparticles in Drosophila melanogaster (Oregon R).

AIMS: In the present study, copper-doped ZnO nanoparticles (doped ZnO NPs Cu) were synthesized, characterized and evaluated for their possible toxic effects in Drosophila melanogaster (Oregon R). METHODS AND RESULTS: X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and energy dispersive X-ray spectrometry confirm the formation of doped ZnO NPs Cu. Doped ZnO NPs Cu (3%) were mixed in the diet at final concentrations of 1, 2, 4 and 8 µg/µl. The starved male flies were allowed to feed on it for 4 days. After completion of the desired duration, climbing ability, activity pattern, activity of acetylcholinesterase (AChE), glutathione (GSH), glutathione-S-transferase (GST), lipid peroxidation (LPO), total protein content and caspases were studied. SDS-PAGE was also performed for whole fly homogenate of control as well as treated flies. No loss in the climbing and activity pattern was observed at the selected doses of doped ZnO NPs Cu. No significant change in the levels of AChE, GSH, GST, LPO, caspase 9/3 and total protein content was observed. The brain sections showed no gross changes in the structure and SDS-PAGE patterns also revealed no change in the protein expression. CONCLUSIONS: The results suggest that doped ZnO NPs Cu are non-toxic at 1, 2, 4 and 8 µg/µl of concentration in D. melanogaster.

Antigenotoxic effect of the Plumbago zeylanica extract against the genotoxic damage induced by potassium canrenoate in cultured human peripheral blood lymphocytes.

In India, natural preparations derived from the plants are widely use for the treatments of various diseases. Hence, it becomes necessary to assess the modulating action of the plant extract when associated with other substances. Potassium canrenoate (PC) is a synthetic steroid and is used in the treatment of hypertension. It is not only a genotoxic agent, but also a tumor-initiating agent. In the present study, the effect of various doses (i.e., 5, 10, 20, and 30 µM) of PC were studied for their genotoxic effects in the presence of S9 mix in cultured human lymphocytes, using mitotic index, chromosomal aberrations, sister chromatid exchanges, and replication index as parameters. PC was found to be genotoxic at 20 and 30 µM. Treatment of 30 µM of PC was given along with different doses of Plumbago zeylanica extract (i.e., 107.5, 212.5, 315, and 417 µg/mL) of the culture medium. A dose-dependent decrease in the genotoxic effects of PC was observed. The result suggested that the plant extract per se does not have genotoxic potential, but can modulate the genotoxicity of PC in cultured human lymphocytes.

Antigenotoxic effect of allicin against estradiol-17beta-induced genotoxic damage in cultured mammalian cells.

Antigenotoxic activity of allicin, one of the sulphur compounds of garlic (Allium sativum) which possesses antioxidant and thiol disulphide exchange activity, was studied against estradiol-17beta-induced genotoxic damage using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameters. Approximately 10, 20 and 40 microM of estradiol-17beta was tested for its genotoxic effect in the presence of metabolic activation and was found to be genotoxic at 20 and 40 microM. Approximately 20 microM of estradiol-17beta was treated along with 5, 10 and 15 microM of allicin, separately, in the presence of metabolic activation. Similar treatments were given with 40 microM of estradiol-17beta. Treatments along with allicin result in the reduction of CAs and SCEs, suggesting its anti-genotoxic activity in human lymphocytes in vitro against estradiol-17beta-induced genotoxic damage.

Anticlastogenic effect of apigenin in human lymphocytes treated with ethinylestradiol.

In the present study the antigenotoxic effect of apigenin was studied against a genotoxic dose of ethinylestradiol using the damage parameters of chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and cell cycle kinetics (CCK). Human peripheral blood lymphocytes were cultured and treated with 10 microM of ethinylestradiol along with doses of 5, 10, 15 and 20 microM of apigenin. A clear decrease in the genotoxic damage induced by ethinylestradiol was observed with increasing doses of apigenin, suggesting a protective role for apigenin during ethinylestradiol therapy.

Assessment of cell viability, lipid peroxidation and quantification of DNA fragmentation after the treatment of anticancerous drug mitomycin C and curcumin in cultured human blood lymphocytes.

Mitomycin C (MMC) is an antineoplastic agent used to fight a number of different cancers including cancer of the stomach, colon, rectum, pancreas, breast, lung, uterus, cervix, bladder, head, neck, eye and oesophagus. It is a potent DNA cross-linker. The prolonged use of the drug may result in permanent bone marrow damage and other various types of secondary tumors in normal cells. The toxic effect of anticancerous drugs may be reduced if supplemented with natural antioxidants/plant products. With this view, the effect of 5, 10 and 15 microM of curcumin was studied against the genotoxic doses of MMC, i.e. 10 and 20 microM, in cultured human lymphocytes using cell viability, lipid peroxidation and DNA damage quantification as parameters. The treatment of curcumin with MMC results in a significant dose-dependent increase in cell viability and decrease in lipid peroxidation and DNA damage suggesting a protective role of curcumin against the anticancerous drug mitomycin C.

Gene diversity and biochemical markers among some Muslim populations of Uttar Pradesh.

A sample of 312 individuals belonging to Sheikh (80), Pathan (54), Ansari (82), Syed (33), Saifi (33) and Hindu Bania (30) populations were surveyed for four protein and three enzyme loci comprising 12 alleles. The markers used were protein (transferrin, haptoglobin, haemoglobin) and enzyme (lactate dehydrogenase, phosphogluconate dehydrogenase, adenylate kinase). Except caeruloplasmin, variants were found among all loci, though no rare variant appears. The populations show genetic equilibrium for all of the loci. Our gene frequencies show some difference from earlier studies for Muslims in general, there being no biradari wise study among Sunni Muslims earlier done anywhere in India or abroad. Heterozygosity ranged from 0.0123 to 0.1994 (Sheikh), 0.0182 to 0.2046 (Pathan), 0.0239 to 0.1844 (Ansari), 0.0587 to 0.3966 (Syed), 0 to 0.3909 (Bania); the average DST and GST values for the seven marker loci were 0.001032 and 0.00879, respectively. The results are discussed. The gene frequency study shows closer relationship of Ansaris and Saifis with native Hindu Banias, and may reflect on their probable conversion in the not remote past.

Protective effect of ascorbic acid against oxidative damage induced by hydrogen peroxide in cultured human peripheral blood lymphocytes.

Hydrogen peroxide is one of the reactive oxygen species for cellular injury. It is overproduced during oxidative stress and is known to damage proteins, nucleic acids and cell membranes. The present study was aimed to study the protective effect of ascorbic acid against the toxic doses of hydrogen peroxide using lipid peroxidation and cytokinesis blocked micronucleus assay. Hydrogen peroxide was studied at 50, 100 and 200µM and was found to increase a dose dependent increase in lipid peroxidation and micronuclei frequency. The treatment of 100 and 200µM of hydrogen peroxide separately along with 20, 40 and 80µM of ascorbic acid showed a dose dependent decrease in the lipid peroxidation and micronuclei frequency. The results suggest a protective effect of ascorbic acid against the hydrogen peroxide induced oxidative damage in cultured human peripheral blood lymphocytes.

Antigenotoxic effect of nordihydroguaiaretic acid against chlormadinone acetate-induced genotoxicity in mice bone-marrow cells.

Nordihydroguaiaretic acid (NDGA), a phenolic lignan, was tested for its antigenotoxic potential against chlormadinone acetate (CMA)-induced genotoxic damage in mice bone-marrow cells. Doses of about 22.50 mg/kg body weight of CMA were given along with 1, 5 and 10 mg/kg body weight of NDGA intraperitoneally. The treatment resulted in the reduction of sister chromatid exchanges and chromosomal aberrations induced by CMA, suggesting an antigenotoxic potential of NDGA. Earlier studies show that CMA generates reactive oxygen species, responsible for genotoxic damage. The free radical-scavenging property of NDGA is responsible for the reduction of genotoxic damage induced by CMA in mice bone-marrow cells.