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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Santa Cecília Programa de Pós-graduação em Sustentabilidade de Ecossistemas Costeiros e Marinhos Laboratório de Pesquisa em Produtos NaturaisUniversidade Estadual de Campinas Departamento de Fisiologia e Biofísica Laboratório de Produtos NaturaisUniversidade Santa Cecília Laboratório de EcotoxicologiaUniversidade Federal de São Paulo (UNIFESP) Instituto do MarUniversidade Camilo Castelo Branco Instituto de Engenharia BiomédicaUNIFESP, Instituto do MarFAPESP: 2009/01788-5SciEL

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis