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Genotoxicity Studies of the Bracken Fern Constituents Quercetin, Shikimate and Ptaquiloside in vitro in Salmonella typhimurium and in vivo in Rats and Mice.

Ngomuo, Ahmed Juma. (1993) Genotoxicity Studies of the Bracken Fern Constituents Quercetin, Shikimate and Ptaquiloside in vitro in Salmonella typhimurium and in vivo in Rats and Mice. Doctoral thesis, University of Surrey (United Kingdom)..

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Bracken fern (Pteridium aquilinum) causes acute and chronic toxicity in animals, and is associated with a high incidence of stomach and oesophageal tumours in countries where it is consumed as food, yet the toxic constituent(s) has not been unequivocally identified. None of the toxic constituents isolated from bracken have individually reproduced all the disease syndromes typical of the plant. The carcinogenicity of the plant has at one time or another been attributed to quercetin, shikimate and ptaquiloside. Studies to determine whether the genotoxicity of quercetin, shikimate (and its metabolite cyclohexanecarboxylate), and ptaquiloside could be enhanced in combined application were conducted in vitro using Salmonella typhimurium and in vivo using mice and rats. Quercetin was mutagenic in S. typhimurium TA98 and TA100 both in the absence and presence of rat hepatic activating fractions. Induction of rat hepatic metabolising enzymes by pretreatment with Aroclor-1254 did not affect the enhancing effect of microsomal, cytosol or S9 activation. Nor did shikimate or ptaquiloside influence the mutagenicity of quercetin. However, cyclohexanecarboxylate, a gastrointestinal bacterial metabolite of shikimate significantly inhibited quercetin mutagenicity, as did norharman and menadione. Ptaquiloside was mutagenic in TA98 and TA100, but only after preincubation. Its mutagenicity was completely abolished by the activation system prepared from rat liver. Neither quercetin, shikimate nor its metabolite cyclohexanecarboxylate affected the mutagenicity of ptaquiloside. Shikimate and cyclohexanecarboxylate were not mutagenic in the Salmonella mutagenicity test, nor were their activities influenced by norharman. Quercetin, shikimate and cyclohexanecarboxylate were tested for genotoxicity in vivo using the micronucleus test in rats and the unscheduled DNA synthesis in rat gastric mucosal cells. None of these compounds were genotoxic. Simultaneous administration of the compounds did not influence their in vivo genotoxic activity. Plasma concentrations of quercetin after oral or intraperitoneal administration at 200 mg/kg bwt were below 0.1 μg/ml suggesting that the negative in vivo results may have been due to poor bioavailability of the compound. Mitomycin C, which was used as a positive control in the in vivo studies, was strongly genotoxic. Studies were conducted to determine the cytotoxic activity of quercetin, shikimate (and its major metabolite cyclohexanecarboxylate), and ptaquiloside using CHO, 3T3 and NRK cells. All the compounds exhibited a low order of cytotoxicity. The concentration which inhibited cell growth by 50% (IC50) was approximately 1 x 10-4 M and 1 x 10-3 for quercetin and ptaquiloside respectively. The IC50 for shikimate and cyclohexanecarboxylate was approximately 1 x 10-3 M and 1 x 10-2 M respectively. The possible mechanisms involved in the mutagenicity of quercetin, inhibition of mutagenicity by cyclohexanecarboxylate, norharman and menadione and the possible implications in vivo are discussed.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Ngomuo, Ahmed Juma.
Date : 1993
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1993.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:23
Last Modified : 06 May 2020 14:29

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