Worldwide more than 400 plant species are now known that hyperaccumulate various trace metals (Cd, Co, Cu, Mn, Ni, and Zn), metalloids (As) and nonmetals (Se) in their shoots. Of these, almost one-quarter are Brassicaceae family members, including numerous Thlaspi species that hyperaccumulate Ni up to 3% of there shoot dry weight. We observed that concentrations of glutathione, Cys, and O-acetyl-l-serine (OAS), in shoot tissue, are strongly correlated with the ability to hyperaccumulate Ni in various Thlaspi hyperaccumulators collected from serpentine soils, including Thlaspi goesingense, T. oxyceras, and T. rosulare, and nonaccumulator relatives, including T. perfoliatum, T. arvense, and Arabidopsis thaliana. Further analysis of the Austrian Ni hyperaccumulator T. goesingense revealed that the high concentrations of OAS, Cys, and GSH observed in this hyperaccumulator coincide with constitutively high activity of both serine acetyltransferase (SAT) and glutathione reductase. SAT catalyzes the acetylation of l-Ser to produce OAS, which acts as both a key positive regulator of sulfur assimilation and forms the carbon skeleton for Cys biosynthesis. These changes in Cys and GSH metabolism also coincide with the ability of T. goesingense to both hyperaccumulate Ni and resist its damaging oxidative effects. Overproduction of T. goesingense SAT in the nonaccumulator Brassicaceae family member Arabidopsis was found to cause accumulation of OAS, Cys, and glutathione, mimicking the biochemical changes observed in the Ni hyperaccumulators. In these transgenic Arabidopsis, glutathione concentrations strongly correlate with increased resistance to both the growth inhibitory and oxidative stress induced effects of Ni. Taken together, such evidence supports our conclusion that elevated GSH concentrations, driven by constitutively elevated SAT activity, are involved in conferring tolerance to Ni-induced oxidative stress in Thlaspi Ni hyperaccumulators.

Increased glutathione biosynthesis plays a role in nickel tolerance in thlaspi nickel hyperaccumulators

Increased Glutathione Biosynthesis Plays a Role in Nickel Tolerance in Thlaspi Nickel Hyperaccumulators

Lung cancer is the leading cause of cancer related mortality worldwide. Crocetin, saffron plant derivative known to play a role in cancer chemoprevention. In the present study the effects of crocetin was tested against lung cancer-bearing mice in both pre-initiation and post-initiation periods. Healthy male Swiss albino mice (6–8 weeks old) were used throughout the study. Experiment was designed with the treatment regimen of crocetin [20 mg/kg body weight dissolved in dimethyl sulphoxide (DMSO)] for 4 weeks before (pre-initiation) and from 12th week after Benzo(a) pyrene B(a)p (50 mg/kg body weight) induced lung carcinoma(post-initation). The level of lipid peroxidation (LPO) and marker enzymes markedly increased in carcinogen administered animals, which was brought back to near normal by crocetin treatment. The activities of the enzymic antioxidants and glutathione metabolizing enzymes were decreased in B(a)p induced animals and increased upon drug treatment. Crocetin profoundly reverted back the pathological changes observed in cancerous animals. From the results crocetin proves to scavenge free radical and plays an important role in cellular function. Tumor incidence and histopathological studies proves crocetin is a potent antitumour agent.

Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies.

Warfarin is clinically the most widely used oral anticoagulant and its properties have been extensively studied. Assay method for these compounds have until recently been relatively nonspecific. The advent of chromatographically based techniques has enabled re-evaluation of the pharmacokinetics of oral anticoagulants, but most work continues to involve warfarin. The most important recent work has concerned the different anticoagulant potencies and metabolic pathways of the optical isomers of some of these drugs. The effects of age and some diseases on pharmacokinetics of warfarin have been examined but much remains to be done, especially with oral anticoagulants other than warfarin. There are several well established pharmacokinetic drug interactions with warfarin. There is a wide awareness of the drugs most likely to reduce anticoagulant effects by enzyme induction and alternative drugs can be used. Mechanisms of some interactions have been re-investigated. In vivo drug displacement interactions are complicated by the correlation between hepatic clearance of these drugs and the size of the unbound fraction in plasma. The interactions between phenylbutazone and warfarin and metronidazole and warfarin, resulting in potentiation of anticoagulant effect have been suggested to be due mainly to an inhibition of the metabolism of the more potent S isomer of warfarin.

Clinical Pharmacokinetics of Oral Anticoagulants

One of the most promising strategies for cancer prevention today is chemoprevention using readily availablenatural substances from vegetables, fruits, herbs and spices . Among the spices, saffron (Crocus sativus, L) a memberof the large family Iridaceae, has drawn attention because apart from its use as a flavouring agent, pharmacologicalstudies have demonstrated many health promoting properties including radical scavenging, anti- mutagenic andimmuno-modulating effects. In the present study the effects of an aqueous infusion of saffron on two stage skinpapillogenesis / carcinogenesis in mice initiated by 7-12 dimethyl benz[a] anthracin (DMBA) and promoted withcroton oil were investigated. Significant reduction in papilloma formation was found with saffron application in thepre-initation and post-initation periods, and particular when the agent was given both pre- and post-initation. Theinhibition appeared to be at least partly due on modulatory effects of saffron on some phase II detoxifying enzymeslike glutathione-S-transferase (GST) and glutahinoe peroxidase (GPx), as well as catalase (CAT) and superoxidedismutase (SOD).Key Words : Saffron - skin carcinogenesis - detoxification enzymes - chemopreventionprotective effects of saffron extract together with cysteineand vitamin E against cisplatin induced toxicity in rats.However, to our knowledge there has been no systematiccytotoxicity analysis of saffron compounds, crocin, crocetin,picrocrocin, and safranol performed separately. In the presentstudy we the examined the anti carcinogenic effects ofaqueous infusion of saffron, administered orally using twostage skin carcinogenesis model in mice. Since phase IIdetoxification enzymes play a major role in the onset ofcarcinogenesis by helping eliminating the damaging agents,modulatory effects of saffron treatment on a number ofenzyme species in the same model were also ascertained.

Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice.

A spectrophotometric method for the estimation of reserpine in crude drugs and pharmaceutical preparations has been described. The method is capable of detecting microquantities of reserpine (0.25 μg./ml.). It is capable of estimating reserpine in crude drugs, alkaloidal mixtures, reserpine and serpentina tablets. The reserpine content in samples of Dehradun and Bengal varieties of R. serpentina has been found to be 0.117 and 0.103 per cent respectively.

A spectrophotometric method for the estimation of reserpine.

A spectrophotometric method for the estimation of guanethidine sulphate, based on the development of blue colour in alkaline medium after reaction with lithium and sodium molybdophosphotungstate B.P. reagent, is described. The method is more sensitive and rapid than the existing British Pharmacopoeia methods. Both powder and tablets can be estimated by this method.

Spectrophotometric method for the estimation of guanethidine.

The effect of eight tranquillisers, widely differing chemically, on monoamine and l-amino acid oxidases of liver, d-amino acid oxidase of kidney and the catalase of liver, have been investigated. Reserpine was found to stimulate d- and l-amino acid oxidases and to inhibit monoamine oxidase. Rescinnamine was much less effective in this respect. Phenothiazine derivatives showed significant inhibitory action on the catalase activity. Benactyzine and diphenhydramine had a mild inhibitory action on monoamine oxidase while meprobamate and mephenesin did not show any effect.

Observations on the mechanism of action of tranquillisers--a study of their effect on monoamine oxidase, D- and L-amino acid oxidases and catalase.

A spectrophotometric method for the estimation of phenindione in pharmaceutical preparations and body fluids and tissues is described. It has a greater sensitivity than the existing British Pharmacopoeia method. Advantage has been taken of the solubility of the drug in toluene and the sensitivity of measurement has been found to be enhanced by the addition of alcoholic potassium hydroxide solution. This method accurately estimates 1–2 mg. of the substance as opposed to the 300 mg. required for the B.P. method. Further, as little as 2.5 μg./ml. of the substance can be detected in biological fluids after eliminating interfering substances.

A spectrophotometric method for the estimation of phenindione

Detection of Tryptophan Synthesising Enzyme in Rauwolfia serpentina Benth Sm,-The presence of tryptophan synthase, which catalyses the condensation of serine and indole to form tryptophan is mostly demonstrated in microorganisms like neurospora (Tatum, 1944). The observation by Tyler and Schwarting (1954) on the availability of such a system in Claviceps purpurea, which forms indole alkaloids, is interesting. During a detailed study of the biosynthesis of indole alkaloids in Rauwolfia serpentina plants, tryptophan synthesising enzyme was detected. Fresh homogenates of roots and leaves were prepared in M/15, phosphate buffer, pH 7 8 , and the ratio of homogenate to buffer adjusted to 1 : 2. The activity of the enzyme was determined by measuring the rate of disappearance of indole and subsequent formation of tryptophan. Samples containing indole, serine, glutathione, pyridoxal phosphate, enzyme extract and the buffer, were incubated for 4 hr. and the unreacted free indole was extracted with toluene and estimated colorimetrically (Yanofsky, 1955). Tryptophan concentrations were measured in the remaining aqueous liquid by the method of Nason, Kaplan and Colowick (1951). The content of tryptophan formed, corresponded to the quantity of indole disappearing during the reaction (Table I).

B. C. Bose

Papers

A spectrophotometric method for the estimation of reserpine.

Spectrophotometric method for the estimation of guanethidine.

Observations on the mechanism of action of tranquillisers--a study of their effect on monoamine oxidase, D- and L-amino acid oxidases and catalase.

A spectrophotometric method for the estimation of phenindione

Detection of tryptophan synthesising enzyme in Rauwolfia serpentina Benth.