The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(LD)2]I2∙CH3OH (1), [CoLD(NCS)2] (2) and [VOLD(NCS)2]∙C6H5CH3 (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.
IntroductionThe standard therapy for exocrine pancreatic insufficiency (EPI) is porcine-derived pancreatic enzyme replacement therapy (PERT). In the present study we tested a new approach with a mixture of pancreatic-like enzymes of microbial origin (PLEM) in a 1-week efficacy study in EPI pigs. In addition to the conventionally used coefficient of fat and nitrogen absorption (CFA and CNA), parameters that more accurately reflect the nutritional and health status, such as changes in the lipemic index (LI), plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels, and somatic growth, were determined.Material and methodsA PLEM dose containing 120 000 active lipase units, 80 000 active protease units and 12 000 active amylase units (all from Sigma, St. Louis, MO) was given as a powder, twice daily with a meal (40 g fat/meal) to 8 EPI pigs for 7 days. Ten healthy pigs were used as a comparator.ResultsThe PLEM enhanced fat and protein digestion, and reversed growth impairment in EPI pigs. With treatment, CFA and CNA increased by 59% and 43% (p < 0.05), respectively. Although fat and protein absorption were lower than in the comparator, the postprandial blood lipid profile was normal as in healthy pigs. The mucosal thickness significantly increased by 27%, 50% and 26%, in the proximal, middle, and distal jejunum (p < 0.05) with treatment and resembled that of healthy animals.ConclusionsPancreatic-like enzymes of microbial origin supported somatic growth and normalized the postprandial lipid profile. As a measure of efficacy, postprandial LI, TG and NEFA are viable endpoints to be explored in human trials.
Baicalin is a flavonoid that has an influence on molecular processes. It possesses anticancer, anti-inflammatory, antiviral, antioxidative, and antithrombotic properties. It was found that baicalein treatment attenuated the damage of the mammary gland induced by LPS, suppressed the activity of myeloperoxidase, TNFα, and IL-1β in mice with mastitis. The aim of the study was a pilot analysis of baicalin tolerability after intramammary (IMM) administration and its impact on somatic cell count (SCC) after multiple IMM treatment on dairy cows with clinical mastitis. Moreover, the determination of baicalin in milk was performed by the sensitive ultra-high performance liquid chromatography with tandem mass spectrometry. The pharmacokinetic analyses were performed using Phoenix® WinNonlin® 6.4 and ThothPro v 4.1 software. Twelve dairy cows with clinical mastitis were selected for this study. The pharmacodynamic endpoint was SCC level and the clinical investigation was also carried out. Baseline SCC analysis was performed every 24 h among all cows three days before the first dose (B1–B3). After the baseline monitoring, 8 days of treatment (T1–T8) was performed and 8 days within recovery period SCC level was observed (R1–R8). Starting from T1 to T8, a decrease of SCC in relation to baseline was characterized by a declining trend. The presented results confirm the effect of baicalin on the reduction of SCC in mastitis in dairy cows after this therapy. The current study has shown that baicalin accumulation was not confirmed.
Hesperidin (HE), chrysin (CH) and naringenin (NA) are flavonoids, being the most important group of polyphenols, and show anti-inflammatory properties which have been demonstrated on various models. Polyphenols have a lot of biological properties, such as antioxidative, antiviral, immunomodulatory and anticancer activities. However, the effect on mastitis has not been yet described. This research aimed to analyze the tolerability of selected polyphenols after multiple intramammary administrations (IMM) as well as to investigate their potential impact on somatic cell count (SCC) in mastitis dairy cows. The study was performed on 12 Polish Holstein Black-White cows in their 4th – to 6th lactation. Only animals with inflammation in one-quarter of the udder were selected. The selection was based on SCC and clinical assessment. The experiment was performed with multiple IMM administrations with each of these polyphenols in dairy cows affected with mastitis. Polyphenols were administered at a dose of 30 mg/quarter/day. Milk samples for SCC, blood plasma samples for pharmacokinetics and blood hematology and biochemistry (selected blood parameters were tested) were collected at baseline, treatment period and within the recovery period. Positive effects concerning the number of SCC in milk of mastitic cows were confirmed for all tested polyphenols.
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