Much work has been carried out in recent years on the beneficial effect of phenolic compounds which act as natural antioxidants and help to neutralize free radicals. We analysed the antioxidant activity of the rutin (quercetin-3-rhamnosyl glucoside) using different assays including: total antioxidant activity and reducing power, hydroxyl radical scavenging assay, superoxide radical scavenging assay, 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay and lipid peroxidation assay which uses egg yolk as the lipid-rich source. Total antioxidant capacity was determined by the assay based on the decrease in absorbance of β-carotene by the sample. Rutin exhibited strong DPPH radical scavenging activity. At the concentration of 0.05 mg/ml, ascorbic acid (Vc), butylated hydroxytoluene (BHT) and rutin showed 92.8%, 58.8%, and 90.4% inhibition, respectively. In addition, rutin had effective inhibition of lipid peroxidation. Those various antioxidant activities were compared to standard antioxidants such as BHT and Vc.

In vitro antioxidant properties of rutin

An integrated view of cisplatin-induced nephrotoxicity and ototoxicity.

Hazardous effects of chemical pesticides on human health-Cancer and other associated disorders.

Multiple lines of evidence indicate that the platinum-containing cancer drugs enter cells, are distributed to various subcellular compartments, and are exported from cells via transporters that evolved to manage copper homeostasis. The cytotoxicity of the platinum drugs is directly related to how much drug enters the cell, and almost all cells that have acquired resistance to the platinum drugs exhibit reduced drug accumulation. The major copper influx transporter, copper transporter 1 (CTR1), has now been shown to control the tumor cell accumulation and cytotoxic effect of cisplatin, carboplatin, and oxaliplatin. There is a good correlation between change in CTR1 expression and acquired cisplatin resistance among ovarian cancer cell lines, and genetic knockout of CTR1 renders cells resistant to cisplatin in vivo. The expression of CTR1 is regulated at the transcriptional level by copper via Sp1 and at the post-translational level by the proteosome. Copper and cisplatin both trigger the down-regulation of CTR1 via a process that involves ubiquitination and proteosomal degradation and requires the copper chaperone antioxidant protein 1 (ATOX1). The cisplatin-induced degradation of CTR1 can be blocked with the proteosome inhibitor bortezomib, and this increases the cellular uptake and the cytotoxicity of cisplatin in a synergistic manner. Copper and platinum(II) have similar sulfur binding characteristics, and the presence of stacked rings of methionines and cysteines in the CTR1 trimer suggest a mechanism by which CTR1 selectively transports copper and the platinum-containing drugs via sequential transchelation reactions similar to the manner in which copper is passed from ATOX1 to the copper efflux transporters.

/pdf/copper-transporters-and-the-cellular-pharmacology-of-the-4q174uuv1w.pdf

Copper Transporters and the Cellular Pharmacology of the Platinum-Containing Cancer Drugs

Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats.

The genotoxic effects of malathion was evaluated using chromosome aberration, sister chromatid exchange (SCE) and sperm abnormality assays in mice. All the three acute doses (2.5, 5 and 10 mg/kg) of malathion tested in the present study, induced significant dose-dependent increase in the frequency of chromosome aberrations and sperm abnormalities, but did not affect the total sperm count. The highest acute dose induced a >12-fold increase in the frequency of chromosome aberrations, two-fold increase in the frequency of SCEs and four-fold increase in the frequency of sperms with abnormal head morphology following intraperitoneal (i.p.) exposure. Further, a significant increase in the frequency of SCEs was observed, but the increase was not dose-dependent. At higher doses, malathion induced a moderate delay in cell cycle as evident from the increase in average generation time (AGT). The present findings suggest that technical grade malathion is a potent genotoxic agent and may be regarded as a potential germ cell mutagen also.

/pdf/genotoxic-effects-of-malathion-an-organophosphorus-4elat4syvm.pdf

Genotoxic effects of malathion: an organophosphorus insecticide, using three mammalian bioassays in vivo

Cisplatin treatment brings about complete regression of ascites Dalton's lymphoma in mice. In the present study various steps involved during the tumor regression are examined using some biochemical and morphological parameters. During tumor regression, ascites fluid volume decreases sharply and there is an increase in carbohydrates and decrease in protein contents in the ascites supernatant after cisplatin treatment in vivo. Cisplatin treatment brings about definite changes in the arrangement/movement of surface membrane ruffles/blebs of tumor cells and causes infiltration of leukocytes (neutrophils, monocytes, lymphocytes) towards tumor cells. Membrane vesicles and vacuoles are also formed before the disintegration and lysis of tumor cells.

Antitumor effect of cisplatin against murine ascites Dalton's lymphoma.

In present studies the development of chromosomal aberrations, micronuclei in bone marrow cells and sperm head abnormalities were used as mutagenic bioassay in Swiss albino mice treated with cisplatin alone or ascorbic plus cisplatin. It was noted that in the combined treated hosts the frequency of all the mutagenic parameters were always significantly less than that treated with cisplatin alone. These findings suggest a protective role of ascorbic acid against cisplatin induced mutagenic potentials. Interestingly, in combined treated hosts glutathione (GSH) level in bone marrow cells increased significantly which may suggest a possible mechanism of ascorbic acid mediated protection against cisplatin induced mutagenic potentials in the hosts.

Vitamin C mediated protection on cisplatin induced mutagenicity in mice.

Total five plants, three from Mizoram (Dillenia pentagyna, Ageratum conyzoides, Blumea lanceolaria) and two from Meghalaya (Potentilla fulgens, Taxus baccata) were studied for their antitumour activity against murine ascites Dalton's lymphoma (DL) in vivo. Only three plants showed the different magnitude of antitumour activity. Out of these three plants, the antitumour activity was maximally observed with the methanol extract of the stem bark of D. pentagyna as compared to the aqueous extract of the roots of A. conyzoides and aqueous extract of the root of P. fulgens. An increase in glutathione levels in Dalton's lymphoma cells was observed during tumour growth. Changes in glutathione and protein levels were also investigated in the liver and Dalton's lymphoma cells of tumour-bearing mice following the treatment with the extract of D. pentagyna which showed the highest antitumour activity as compared to the other two plant extracts. Glutathione in the liver and DL cells of treated tumour-bearing mice was found to be decreased. The protein concentration in liver and DL cells decreased mainly at 96 hr of treatment. It may be concluded that the natural product of D. pentagyna promises to be more active against Dalton's lymphoma than others and the decrease in glutathione level may be one of the important steps in resulting this antitumour effect.

http://nopr.niscair.res.in/bitstream/123456789/23764/1/IJEB%2042%2810%29%20981-988.pdf

Antitumour activity of some plants from Meghalaya and Mizoram against murine ascites Dalton's lymphoma

The genotoxic effects of carbosulfan were evaluated using chromosome aberration (CA), bone marrow micronucleus (MN) and sperm abnormality assays in mice. All the three acute doses (1.25, 2.5 and 5 mg/kg) of carbosulfan induced significant dose-dependent increase in the frequency of CA ( P P P 7-fold increase in the frequency of CA, >3.5-fold increase in the frequency of micronucleated PCEs and >4.6-fold increase in the frequency of sperms with abnormal head morphology following intraperitoneal exposure as compared to the untreated controls. The present findings suggest that carbosulfan is a potent genotoxic agent and may be regarded as a potential germ cell mutagen also.

Surya Bali Prasad

Papers

Genotoxic effects of malathion: an organophosphorus insecticide, using three mammalian bioassays in vivo

Antitumor effect of cisplatin against murine ascites Dalton's lymphoma.

Vitamin C mediated protection on cisplatin induced mutagenicity in mice.

Antitumour activity of some plants from Meghalaya and Mizoram against murine ascites Dalton's lymphoma

Mutagenic effects of carbosulfan, a carbamate pesticide