Safflower Oil: An Integrated Assessment Of Phytochemistry, Antiulcerogenic Activity, And Rodent And Environmental Toxicity

Gastric ulcers are a significant medical problem and the development of complications lead to significant mortality rates worldwide. In Brazil, Carthamus tinctorius L., Asteraceae, seeds essential oil, the safflower oil, is currently used as a thermogenic compound and as treatment for problems related to the cardiovascular system. In this study, by Raman spectroscopy, it was shown that oleic and linoleic acids are the compounds present in higher concentrations in the safflower oil. We demonstrated that safflower oil (750 mg/kg, p.o.) decrease the ulcerogenic lesions in mice after the administration of hydrochloric acid-ethanol. The gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) in mice treated with cholinomimetics were treated with four different doses of safflower oil, of which, the dose of 187.5 mg/kg (p.o.) showed significant antiulcerogenic properties (p < 0.01). Moreover, the safflower oil at doses of 187.5 mg/kg (i.d.) increased the pH levels, gastric volume (p < 0.01) and gastric mucus production (p < 0.001), and decreased the total gastric acid secretion (p < 0.001). The acute toxicity tests showed that safflower oil (5.000 mg/kg, p.o.) had no effect on mortality or any other physiological parameter. Ecotoxicological tests performed using Daphnia similis showed an EC50 at 223.17 mg/l, and therefore safflower oil can be considered “non-toxic” based on the directive 93/67/EEC on risk assessment for new notified substances by European legislation. These results indicate that the antiulcer activity of Safflower oil may be due to cytoprotective effects, which serve as support for new scientific studies related to this pathology.245538544ABNT, Ecotoxicologia aquatica: Toxicidade aguda-metodo de ensaio com (2004) Daphnia, 21p. , spp (Cladocera, Crustacea). NBR 12713, Rio de JaneiroAmandeep, K., Robin, S., Ramica, S., Sunil, K., Peptic ulcer: A review of etiology and pathogenesis (2012) Int. J. Clin. Pharm, 3, pp. 34-38Arakawa, T., Watanabe, T., Tanigawa, T., Tominaga, K., Fujiwara, Y., Morimoto, K., Quality of ulcer healing in gastrointestinal tract: Its pathophysiology and clinical relevance (2012) World J. Gastroenterol, 18, pp. 4811-4822Bae, C.S., Park, C.H., Cho, H.J., Han, H.J., Kang, S.S., Choi, S.H., Uhm, C.S., Therapeutic effects of safflower (Carthamus tinctorius L.) seed powder on osteoporosis (2002) Korean J. Electron. Microscopy, 32, pp. 285-290Baeten, V., Dardenne, P., Aparicio, R., Interpretation of Fourier transform Raman spectra of the unsaponifiable matter in a selection of edible oils (2001) J. Agric. Food Chem, 49, pp. 5098-5107Brito, A.R.M.S., (1994) Manual de ensaios toxicologicos in vivo, 116p. , 1a ed., Campinas, Editora UnicampCEC, (1996) Technical guidance document in support of commission directive 93/67/EEC on risk assessment for new notified substances, , Part II, environmental risk assessment. Commission of the European Communities, Luxembourg: Office for official publication of the European CommunitiesCorley, D.A., Kubo, A., Zhao, W., Quesenberry, C., Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients (2010) Gastroenterol, 139, pp. 93-101Deplege, M., Pharmaceuticals: Reduce drug waste in the environment (2011) Nature, 36, p. 478Fent, K., Weston, A.A., Caminada, D., Ecotoxicology of human pharmaceuticals (2006) Aquat. Toxicol, 76, pp. 122-159George, P., Concerns regarding the safety and toxicity of medicinal plants-An overview (2011) J. Appl. Pharm. Sci, 1, pp. 40-44Gilbert, N., Drug-pollution law all washed up (2012) Nature, 491, pp. 503-504Isidori, M., Parrella, A., Pistillo, P., Temussi, F., Effects of ranitidine and its photoderivatives in the aquatic environment (2009) Environ. Intern, 35, pp. 821-825Jain, K.S., Shah, A.K., Bariwal, J., Shelke, S.M., Kale, A.P., Jagtap, J.R., Bhosale, A.V., Recent advances in proton pump inhibitors and management of acid-peptic disorders (2007) Bioorg. Med. Chem, 15, pp. 1181-1205Kim, S.K., Cha, J.Y., Jeong, S.J., Chung, C.H., Choi, Y.R., Cho, Y.S., Properties of the chemical composition of safflower (Carthamus tinctorius L.) sprout (2000) Korean J. Life Sci, 10, pp. 68-73Madanick, R.D., Proton pump inhibitor side effects and drug interactions: Much ado about nothing? Cleve (2011) Clin. J. Med, 78, pp. 39-49Malfertheiner, P., Chan, F.K.L., McColl, K.E.L., Peptic ulcer disease (2009) Lancet, 374, pp. 1449-1461Mizui, T., Doteuchi, M., Effect of polyamines on acidified ethanol-induced gastric lesion in rats (1983) Jpn. J. Pharmacol, 33, pp. 939-945Olfert, D., Cross, B.M., McWilliam, A.A., (1993) Guide to the Care and Use of Experimental Animal, 213p. , Canadian Council on Animal Care, OntarioPintao, A.M., Da Silva, I.F., A verdade sobre o acafrao (2008) Workshop Plantas Medicinais e Fitoterapeuticas nos Tropicos. IICT/CCCM, 29, pp. 30, 31. , de Outubro, 1-19Rainsford, K.D., The effects of aspirin and other non-steroid anti-inflammatory/analgesic drugs on gastro-intestinal mucus glycoprotein biosynthesis in vivo: Relationship to ulcerogenic actions (1978) Biochem. Pharmacol, 27, pp. 877-885Rudolphi, S., Becker, H.C., Schierholt, A., Witzke-Ehbrecht, S.V., Improved estimation of oil, linoleic and oleic acid and seed hull fractions in safflower by NIRS.J (2012) Am. Oil Chem. Soc, 89, pp. 363-369Santos, L.H.L.M., Araujo, A.N., Fachinia, A., Pena, A., Delerue-Matos, C., Montenegro, M.C.B.S.M., Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment (2010) J. Hazard Mater, 175, pp. 45-95Saraf, A., Saraf, S., Legal regulations of complementary and alternative medicines in different countries (2012) Pharmacogn. Rev, 6, pp. 154-160Shay, H., Komarov, S.A., Fels, S.S., Meranze, D., Gruenstein, M., Siplet, H., A simple method for the uniform production of gastric ulceration in the rat (1945) Gastroenterol, 5, pp. 43-61Silveira, F.L., Silveira, L., Jr., Villaverde, A.B., Pacheco, M.T.T., Pasqualucci, C.A., Use of dispersive Raman Spectroscopy in the determination of unsaturated fat in commercial edible oil-and fat-containing industrialized foods (2010) Instrum. Sci. Technol, 38, pp. 107-123Silveira, L., Silveira, F.L., Bodanese, B., Zangaro, R.A., Pacheco, M.T.T., Discriminating model for diagnosis of basal cell carcinoma and melanoma in vitro based on the Raman spectra of selected biochemicals (2012) J. Biomed. Opt, 17Stachowska, E., Dolegowska, B., Dziedziejk, V., Rybicka, M., Kaczmarczyh, M., Bober, J., Rac, M., Chlubek, D., Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugate linoleic acids (CLA) in human macrophages (2009) J. Physiol. Pharmacol, 60, pp. 77-85Sun, X.B., Matsumoto, T., Yamada, H., Effects of a polysaccharide fraction from the root of Bupleurum falcatum L on experimental gastric ulcer models in rats and mice (1991) J. Pharm. Pharmacol, 43, pp. 669-704Szelenyi, I., Thiemer, K., Distention ulcer as a model for testing of drugs for ulcerogenic side effects (1978) Arch. Toxicol, 41, pp. 99-105Takeuchi, H., Matsuo, T., Tokuyama, K., Shimomura, Y., Suzuki, M., Diet-induced thermogenesis is lower in rats fed a lard diet than in those fed a high oleic acid safflower oil diet, a safflower oil diet or a linseed oil diet (1995) J. Nutr, 125, pp. 920-925US EPA, (2002) Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms, 266p. , 5th ed. United States Environmental Protection Agency, EPA-821-R-02-012Webb, S., A data-based perspective on the environmental risk assessment of human pharmaceuticals I. collation of available ecotoxicity data and II. aquatic risk characterisation (2001) Pharmaceuticals in the environment sources, fate, effects and risks, pp. 175-230. , Kummerer K editor. 1st ed. Heidelberg, Germany: Springer-Verlag pWHO, (1997) Adverse Drug Reaction Database, , World Health Organization, Uppsala Sweden. 36. Institute of Safe Medication Practices Medication Safety Alert. June 4, V 01. 2 No. llWHO, (2002) Monographs on the Evaluation of Carcinogenic Risks to Humans, , (Some Traditional Herbal Medicines), World Health Organization Vol. 82, IARC Press Lyon, FranceZapata-Colindres, J.C., Zepeda-Gomez, S., Montano-Loza, A., Jesus-Villalobos, J.E., Valdovinos-Andraca, F., The association of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in peptic ulcer disease (2006) Can. J. Gastroenterol, 20, pp. 277-28

Application of Neutral Red Retention Assay in the clam Ruditapes philippinarum and the crab Carcinus maenas as a screening tool for sediment quality assessment in marine environment

Dredged material can cause several negative impacts to the ecosystems. Its management is a key issue for the protection of the aquatic environments. Sediment quality guidelines alone are not able to estimate the potential adverse effects that contaminants bound to sediment can cause. The in situ approach using caged bioindicator species has been chosen lately as a new sensitive tool for the assessment of dredged material. In a tier testing approach, Neutral Red Retention Assay (NRRA) has been applied as a screening tool in order to detect adverse changes in health status associated to contaminated environments. Nevertheless, to the authors' knowledge, little is known about the application and validation of NRRA in sediment bioindicator species and under field conditions. Caged Ruditapes philippinarum and Carcinus maenas were exposed during 28 days to 3 potentially contaminated sites in the Algeciras Bay (SW Spain) and to a reference site in the Cadiz Bay (SW Spain). Health status of exposed organisms was measured through NRRA in haemolymph samples. No significant differences of Neutral Red Retention Time (NRRT) were measured neither in clams nor in crabs over time in the organisms from control site (70 ± 10min). However significant differences (p < 0.05) were found at the end of the exposure period in clams and crabs exposed to contaminated sediments from Algeciras Bay, showing a decrease of NRRTs from 30 to 70% compared to the control organisms. The results obtained confirmed the use of NRRA as a suitable and sensitive method to be used in the assessment of sediment quality