Daidzein nanosuspension in combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in vitro evaluation.

Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-ß1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.

Effects of Emulsion Formulations of Oleuropein Isolated from Ethanol Extract of Olive Leaf in Diabetic Rats.

This study was designed to investigate the effects of emulsion formulations of oleuropein isolated from ethanol extract of olive leaf in streptozotocin-diabetic rats. The rats were treated with the administration of the emulsion containing oleuropein at a low (150 mg/kg b.wt.) and high (225 mg/kg b.wt.) dose for 30 days. At the end of the study, blood samples were drawn from the heart of the rats to determine blood glucose, alanine transaminase, and aspartate transaminase levels. In addition, their liver tissues were dissected to determine the levels of glutathione and thiobarbituric acid-reactive substances, and superoxide dismutase activity. According to the results for both dose treatments, a statistically significant increase in superoxide dismutase activities and glutathione levels of the treated diabetic rats was observed when compared with those of the diabetic control rats. On the other hand, a statistically significant decrease in the levels of thiobarbituric acid-reactive substances, aspartate transaminase and alanine transaminase of the treated diabetic rats was determined. It should be highlighted that the administrations at the high dose were more effective compared to that of the low dose. Furthermore, a substantial decrease in the blood glucose levels of the diabetic rats exposed to the high dose was observed.

Ionic high-osmolar contrast medium causes oxidant stress in kidney tissue: partial protective role of ascorbic acid.

It has been known that contrast medium may cause contrast-induced nephropathy in risk groups. This study sought to establish possible effects of ionic high-osmolar contrast medium administration with or without antecedent cisplatin treatment on oxidant/antioxidant status in rat kidney tissues, as well as to investigate a possible protective role of antioxidant ascorbic acid in this regard. Thirty-five female, 14-week-old Wistar-albino rats were used in this study. They were divided into five groups of seven rats (sham, contrast, contrast + ascorbic acid, contrast + cisplatin, and contrast + cisplatin + ascorbic acid). Ascorbic acid was given in a dose of 250 mg/kg/day orally throughout the study period, and cisplatin (10 mg/kg) as a single i.v. dose on the fourth day. Ionic high-osmolar contrast medium (3 gr/kg iodine as a single dose) was administered by i.v. route on the fifth day. After the animals were sacrificed on the sixth day, their kidney tissues were removed surgically to be used in the analyses. Malondialdehyde (MDA) level and activities of antioxidant (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px] and catalase [CAT]) and oxidant (xanthine oxidase [XO]) enzymes were measured in these samples. Serum urea and creatinine levels were measured to evaluate kidney functions. Histopathological investigation of the tissues was also performed. It was observed that contrast medium administration caused increases in MDA levels in the kidney tissues, either alone or together with antecedent cisplatin treatment. However, ascorbic acid prevented the increases in MDA levels in the kidney tissues. Histopathological findings revealed that ionic high-osmolar contrast medium administration alone led to mild acute structural damage, but contrast medium administration together with antecedent cisplatin usage caused severe tubular necrosis. Ascorbic acid supplementation prevented these changes, to a great extent. The results suggest that ionic high-osmolar contrast medium administration, either alone or together with antecedent cisplatin treatment, leads to accelerated oxidative reactions in rat kidney tissues, and ascorbic acid protects in part the kidney tissues against this oxidant stress.