J Nutr Sci Vitaminol (Tokyo). 2001 Apr;47(2):126-31.
Acute toxicity and mutagenicity study on branched corn syrup and evaluation of its laxative effect in humans.
Kishimoto Y, Wakabayashi S, Matsuda I, Fudaba H, Ohkuma K.
Research Institute, Matsutani Chemical Industry Company Ltd., Itami, Hyogo, Japan.
We developed a branched corn syrup (BCS, average molecular weight: 500, content of indigestible portion: 45%) by heat treatment of indigestible dextrin with hydrochloric acid. To confirm the safety of BCS, we conducted both an acute toxicity test and a mutagenicity test. Moreover, we observed gastroenteric effects of BCS in fifty healthy humans. The results are summarized as follows. 1) There was no death observed after oral administration of BCS in Sprague-Dawley-strain rats. Lethal dose (LD)50, value was estimated to be more than 10 g/kg body weight. 2) No mutagenicity was observed in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or Escherichia coli WP2uvrA. 3) Fifty adults were divided into five groups often (five of each sex) and orally administered BCS at 0.2, 0.3, 0.4. 0.5 and 0.6 g/kg body weight as indigestible portion. Although no diarrhea was observed in females, BCS at 0.6 g/kg as indigestible portion caused diarrhea in two out of five males. The maximum non-effective dose of indigestible portion of BCS was estimated to be 0.5 g/kg in males and more than 0.6 g/kg in females.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11508703&dopt=Abstract constipation laxative
J Pathol. 2001 Aug;194(4):493-9.
Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use?
van Gorkom BA, Karrenbeld A, van der Sluis T, Zwart N, de Vries EG, Kleibeuker JH.
Department of Gastroenterology, University Hospital, 9700 RB Groningen, The Netherlands.
Chronic sennoside use induces melanosis coli (MC) and possibly increases colorectal cancer risk. Sennosides alter colonic crypt length, proliferative activity, and bcl-2 expression 18 h after administration. To investigate possible mechanisms for carcinogenesis, the effects of acute sennoside use and the presence of MC on colorectal epithelium were studied. Colorectal biopsies from 15 subjects receiving sennosides 6 h before sigmoidoscopy (Sen), 15 controls (NSen), and 27 with MC [11 moderate (MMC) and 16 severe (SMC)]. were analysed for degree of apoptosis (H&E staining), immunohistochemical p53, p21/WAF and bcl-2 expression, and proliferative activity (labelling index, LI). Apoptosis (p=0.0004), intensity of p53 staining (p=0.01), and p21/WAF expression (p=0.008) were increased in Sen and SMC compared with NSen and MMC. p53 expression was increased in Sen (p=0.004). No difference in bcl-2 expression or LI was observed. Crypts were shorter in Sen (p=0.05) and longer in SMC (p=0.04) than in NSen. It is concluded that sennosides acutely induce apoptosis of colonic epithelial cells, presumably by a p53, p21/WAF-mediated pathway, resulting in shorter crypts. In severe melanosis coli, apoptosis seems to be delayed, causing longer crypts without a rise in proliferative activity or bcl-2 expression. This escape from a presumably protective mechanism may enhance the risk of carcinogenesis during chronic sennoside use. Copyright 2001 John Wiley & Sons, Ltd.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11523059&dopt=Abstract constipation laxative
Photochem Photobiol. 2001 Aug;74(2):226-36.
Generation of free radicals by emodic acid and its [D-Lys6]GnRH-conjugate.
Rahimipour S, Bilkis I, Peron V, Gescheidt G, Barbosa F, Mazur Y, Koch Y, Weiner L, Fridkin M.
Departments of Organic Chemistry and Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
In an attempt to develop an efficient chemotherapeutic agent targeted at malignant cells that express receptors to gonadotropin releasing hormone (GnRH) we coupled [D-Lys6]GnRH covalently to an emodin derivative, i.e. emodic acid (Emo) to yield [D-Lys6(Emo)]GnRH. Emodin is a naturally occurring anthraquinone which is widely used as a laxative and has other versatile biological activities. Physico-chemical studies employing electron paramagnetic resonance and electrochemistry of the conjugate as well as the (Emo) moiety showed that these compounds could be easily reduced either chemically, photochemically or enzymatically to their corresponding semiquinones. In the presence of oxygen the semiquinones generated reactive oxygen species (ROS), mainly superoxide and hydroxyl radicals, which were detected by the spin trapping method. Moreover, upon irradiation with visible light these compounds produced ROS and a highly reactive excited triplet state of Emo, which by itself may cause the oxidation of certain electron acceptors such as amino acids and bases of nucleic acids. Thus, [D-Lys6]GnRH-photosensitizer conjugates may be potentially used for targeted photodynamic chemotherapy aimed at treating cancer cells that carry GnRH receptors. These conjugates may also induce cytotoxicity in the dark similar to common conventional chemotherapeutic agents. The peptidic moiety, [D-Lys6]GnRH, was found to be stable toward highly reactive ROS generated either from enzymatic reduction or upon photoirradiation. The physico-chemical properties of Emo were only marginally influenced by the peptidic [D-Lys6]GnRH carrier.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11547560&dopt=Abstract constipation laxative
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