The purpose of this study was to develop, optimize, and fully validate a high-sensitivity methodology using UHPLC-MS/MS to simultaneously quantify hesperidin and naringenin in microsamples (100 µL) of murine plasma after intragastric administration of single pure flavonoids and a mixture. The optimization process allowed for high sensitivity with detection limits of approximately picogram order using an electrospray ionization (ESI) source in negative mode and an experiment based on multiple reaction monitoring (MRM). The validation parameters showed excellent linearity and detection limits, with a precision of less than 8% and a recovery of over 90%. This methodology was applied to compare the pharmacokinetic parameters for the administration of hesperidin and naringenin in individual form or in the form of a mixture. The results showed an absence of significant effects (p > 0.05) for Tmax and Cmax; however, the AUC presented significant differences (p < 0.05) for both flavonoids when administered as a mixture, showing an improved absorption ratio for both flavonoids.

Photochemical degradation of methylparathion (O,O,-dimethyl O-4 nitrophenylphosphorothioate) in the presence of humic acid between pH 2 and 7 was monitored by differential pulse polarography. Humic acid was not electro-active under the experimental conditions used in this study. Only the pesticide and its main degradation product at pH 2 exhibited polarographic signals. Photolysis of methylparathion in acid media was sensitized by humic acid since the pesticide did not degrade in the absence of this compound. Methylparathion degradation in the presence of humic acid was observed at each of the studied pHs. The reaction was first-order with rate constant values ranging from 2 x 10(-3) to 6.3 x 10(-3) min(-1).

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD50 was LD50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.

Trichomonas vaginalis is the etiological agent of human trichomoniasis. Metronidazole has high treatment success rate among trichomoniasis patients. However, metronidazole-resistant T. vaginalis has been reported, contributing in an increasing number of refractory cases. The mechanism of metronidazole resistance in this parasite is still unclear. In the vaginal environment, where the microaerophilic conditions prevail but the iron concentration is constantly fluctuating, the metronidazole resistance profile of T. vaginalis could be altered. In this study, we developed metronidazole-resistant strains of T. vaginalis and evaluate if iron availability is important to the action of the drug. The modulation of iron levels and iron chelation affected the actions of metronidazole both in susceptible and resistant strains. Interestingly, the early resistant strains exhibited minor iron content. The results of transcription analysis in the early resistant strains showed dysregulation in the expression of genes that codified proteins involved in iron transporter, iron-sulfur cluster assemblage, and oxidative stress response, which could not be observed in the late resistant and susceptible strains. Our results indicate that iron content plays an important role in the metronidazole action in T. vaginalis and likely to be related to iron-sulfur proteins involved in metronidazole activation and oxidative stress via Fenton reaction.

Phenolic compounds and major steviol glucosides by HPLC-DAD-RP and invitro evaluation of the biological activity of aqueous and ethanolic extracts of leaves and stems: S.rebaudiana Bertoni (creole variety INIFAP C01),