Baraka OZ et al. (1996) Eur J Clin Pharmacol "Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus."

Marschke CK, Williams JF, Baraka OZ, Mahmoud BM, Homeida MM, Geary TG

[Eur J Clin Pharmacol, 1996]

OBJECTIVE: To determine the distribution of ivermectin in plasma and tissues of onchocerciasis patients following a single oral dose of 150 micrograms kg-1. SETTING: Medical Department at Soba University Hospital, Khartoum. PATIENTS: Twenty five patients and fourteen healthy volunteers. METHODS: Serial blood samples were obtained from both groups. Tissue samples were removed from various patients as full thickness skin punch biopsies or during nodulectomy. Ivermectin concentration was determined by radioimmunoassay. RESULTS: The plasma pharmacokinetic variables for patients were; maximum plasma concentration 52.0 ng ml-1; time to achieve maximum concentration, 5.2 h.; elimination half life, 35.0 h; and the area under the plasma concentration curve versus time, 2852 ng.h.ml-1. In healthy volunteers, the plasma ivermectin distribution was similar to that in patients, and both groups showed a tendency for a second rise in plasma concentration of the drug suggestive of enterohepatic recirculation. Ivermectin was detected in tissues obtained from patients. Fat showed the highest and most persistent levels, whilst values for skin, nodular tissues, and worms were comparable. Subcutaneous fascia contained the lowest concentrations. CONCLUSIONS: Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.

Lee JH et al. (2011) J Ginseng Res "Effects of Minor Ginsenosides, Ginsenoside Metabolites, and Ginsenoside Epimers on the Growth of Caenorhabditis elegans."

Kang J, Choi SH, Kim HJ, Shin TJ, Hwang SH, Nah SY, Ahn JY, Lee BH, Lee JH, Park CW

[J Ginseng Res, 2011]

In the previous report, we have demonstrated that ginsenoside Rc, one of major ginsenosides, is a major component for the restoration for normal growth of worms in cholesterol-deprived medium. In the present study, we further investigated the roles of minor ginsenosides, such as ginsenoside Rh1 and Rh2, ginsenoside metabolites such as compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) and ginsenoside epimers such as 20(R)- and 20(S)-ginsenoside Rg3 in cholesterol-deprived medium. We found that ginsenoside Rh1 almost restored normal growth of worms in cholesterol-deprived medium in F1 generation. However, supplement of ginsenoside Rh2 caused a suppression of worm growths in cholesterol-deprived medium. In addition, CK and PPD also slightly restored normal growth of worms in cholesterol-deprived medium but PPT not. In experiments using ginsenoside epimers, supplement of 20(S)- but not 20(R)-ginsenoside Rg3 in cholesterol-deprived medium also almost restored worm growth. These results indicate that the absence or presence of carbohydrate component at backbone of ginsenoside, the number of carbohydrate attached at carbon-3, and the position of hydroxyl group at carbon-20 of ginsenoside might plays important roles in restoration of worm growth in cholesterol-deprived medium.

Huang J et al. (2020) Int J Mol Sci "Short-Term Mild Temperature-Stress-Induced Alterations in the C. elegans Phosphoproteome."

Wu Z, Huang J, Zhang X

[Int J Mol Sci, 2020]

Exposure to mild early-life stresses can slow down aging, and protein phosphorylation might be an essential regulator in this process. However, the mechanisms of phosphorylation-based signaling networks during mild early-life stress remain elusive. Herein, we systematically analyzed the phosphoproteomes of <i>Caenorhabditis elegans</i>, which were treated with three mild temperatures (15 C, 20 C, and 25 C) in two different short-term groups (10 min and 60 min). By utilizing an iTRAQ-based quantitative phosphoproteomic approach, 18,187 phosphosites from 3330 phosphoproteins were detected in this study. Volcano plots illustrated that the phosphorylation abundance of 374 proteins and 347 proteins, were significantly changed at 15 C and 25 C, respectively. Gene ontology, KEGG pathway and protein-protein interaction network analyses revealed that these phosphoproteins were primarily associated with metabolism, translation, development, and lifespan determination. A motif analysis of kinase substrates suggested that MAPK, CK, and CAMK were most likely involved in the adaption processes. Moreover, 16 and 14 aging-regulated proteins were found to undergo phosphorylation modifications under the mild stresses of 15 C and 25 C, respectively, indicating that these proteins might be important for maintaining long-term health. Further lifespan experiments confirmed that the candidate phosphoproteins, e.g., EGL-27 and XNP-1 modulated longevity at 15 C, 20 C, and 25 C, and they showed increased tolerance to thermal and oxidative stresses. In conclusion, our findings offered data that supports understanding of the phosphorylation mechanisms involved in mild early-life stresses in <i>C. elegans</i>. Data are available via ProteomeXchange with identifier PXD021081.