par Sinaeve, Sebastien 
;Husson, Cécile ;Antoine, Marie-Hélène ;Welti, Stéphane;Decock, Cony;Delporte, Cédric ;Stévigny, Caroline ;Nortier, Joëlle
Référence 11th International Medicinal Mushroom Conference (IMMC 11) (11: 27-30/09/2022: Belgrade, Serbie)
Publication Non publié, 2022-09-29
;Husson, Cécile ;Antoine, Marie-Hélène ;Welti, Stéphane;Decock, Cony;Delporte, Cédric ;Stévigny, Caroline ;Nortier, Joëlle Référence 11th International Medicinal Mushroom Conference (IMMC 11) (11: 27-30/09/2022: Belgrade, Serbie)
Publication Non publié, 2022-09-29
Communication à un colloque
| Résumé : | Cisplatin is currently used as a first-line cancer treatment, such as testicular, ovarian orpulmonary cancers. Their nephrotoxicity remains a real problem. Acute kidney injury inducedby cisplatin is located on proximal tubular cells, causing necrosis and possibly subsequentinterstitial fibrosis and chronic dysfunction. These severe side effects can lead to a cessationof the patient’s treatment. Currently, there is no effective prophylactic action to reduce cisplatinnephrotoxicity, beside hyperhydration of the patient [1].The aim of the present work is therefore to identify new prophylactic therapy. For this, naturalproducts can be studied, in this case, the interest of potential new medicinal mushroomsextracts. Among 13 mushroom extracts, the methanolic extracts of Ganoderma parvigibbosumWelti & Courtecuisse, Ganoderma tuberculosum Murrill and their association were selected tostudy their effects on human proximal tubular cells (HK-2) intoxicated with cisplatin.HK-2 cells are grown in 75cm² sterile flasks using DMEM low glucose (1mg/mL), supplementedwith FBS (10%), L-Glutamin and a mix of Penicillin/Streptomycin. Dried mushrooms weregrounded and extracted 3 times by methanol, evaporated extracts are stored at -20°C. Aviability assay allowed to determine the work concentration of extracts range have been done.After that, tests were performed after a pretreatment of 1h with the extracts before addingcisplatin at a concentration of 20 μM. Viability assays (CCK-8) and antioxidant activity (DPPH)were done in 96-well. The intracellular concentration of β-catenin and calcium, Caspase-3,p53, cytochrome C, IL-6, NFκB, the membranal expression of KIM-1 and finally the ROSproduction (H2DCFDA) were studied by flow cytometry.Tests have shown that methanolic extracts of G. parvigibbosum and G. tuberculosum (10μg/mL) and their association (5 + 5 μg/mL) prevented the loss of viability after a 24hincubation. They also have prevented the apoptosis and the induction pathway after 24h. G.parvigibbosum and the association of the two mushrooms extracts have also prevented theincrease of caspase-3 and intracellular β-catenin. Finally, G. parvigibbosum was the only toprevent the ROS overproduction and having a scavenger activity at work concentration. Noneof them showed a prevention in the increase of IL-6 and NFκB or the membrane expression ofKIM-1.Ganoderma parvigibbosum appears to be therefore more beneficial than Ganodermatuberculosum and the association of the two mushrooms extracts by acting also on the ROSoverproduction. In conclusion, in this study, the extracts have shown a significant activity onthe prevention of the pro-apoptosis pathway rather than a pro-inflammatory prevention. Furtherinvestigation about metabolomic analysis are undergoing and will be presented to identify theprecise activity and chemical content of these extracts.References[1] Bunel V., et al, Pharm Biol. 2015 |
