Browsing by Author "de Lourdes Bastos, Maria"
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- Chemical characterization and in vitro cyto- and genotoxicity of ‘legal high’ products containing Kratom (Mitragyna speciosa)Publication . Oliveira, Ana Sofia; Fraga, Sónia; Carvalho, Félix; Araújo, Ana Margarida; Pereira, Cristiana Costa; Teixeira, João Paulo; de Lourdes Bastos, Maria; de Pinho, Paula GuedesKratom is a popular ‘legal high’ mainly constituted by alkaloids extracted from the Mitragyna speciosa plant with mitragynine (MG) as the dominant active substance. The increasing use of Kratom for recreational purposes has alerted risk assessment bodies of the lack of information on the real composition and its potential health risks. The present study aimed to determine and compare the MG composition of 13 commercial products of Kratom sold online and in “smartshops”, by gas chromatography–mass spectrometry. For the first time, the cytotoxicity induced by pure MG and Kratom, extracts was evaluated in in vitro models of human intestinal (Caco-2) and neuronal (SH-SY5Y) cells after 6 and 24 h. Genotoxicity was also evaluated in intestinal Caco-2 cells following 24 h of exposure to subtoxic concentrations using the comet assay. The obtained results revealed an inconsistency between the information (‘power’) provided in labels and the MG content. Cytotoxicity tests revealed a concentration-dependent decrease in cell viability in both cellular models, with the SH-SY5Y cells being more sensitive to the Kratom extracts. The resin and the ‘powered extracts’ were the most cytotoxic samples, with IC50 values significantly lower than the leaf extracts and pure MG (P < 0.0001 vs. leaf extracts and MG). In addition, significant DNA damage was observed in Caco-2 cells exposed to these extracts but not to pure MG, which suggests that other substances present in the extracts or interactions involving Kratom components might be responsible for the observed effects.
- l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in ratsPublication . Leal, Joana; Teixeira-Santos, Luísa; Pinho, Dora; Afonso, Joana; Carvalho, Jorge; de Lourdes Bastos, Maria; Albino-Teixeira, António; Fraga, Sónia; Sousa, TeresaWe evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg-1·day-1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg-1.min-1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.