Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells.
Journal Title: Pharmacological Reports - Year 2011, Vol 63, Issue 3
Abstract
Cisplatin is a highly effective chemotherapeutic agent, but it has significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to cisplatin. The present study examined the effects of phloretin, a natural polyphenolic compound found in apples and pears, on cisplatin-induced apoptosis. We found that phloretin induced the expression of heme oxygenase-1 (HO-1) protein in a concentration- and time-dependent manner. Phloretin induced nuclear factor-E2-related factor 2 (Nrf2) nuclear translocation, and dominant-negative Nrf2 attenuated phloretin-induced expression of HO-1. Phloretin activated the JNK, ERK and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in phloretin-induced HO-1 expression. Phloretin protected the cells against cisplatin-induced apoptosis. The protective effect of phloretin was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Furthermore, phloretin pretreatment inhibited mitochondrial dysfunction and the activation of caspases. These results demonstrate that the expression of HO-1 induced by phloretin is mediated by both the JNK pathway and Nrf2; the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells.
Authors and Affiliations
Byung-Min Choi, Xiao Chen, Shang Gao, Rizhe Zhu, Bok-Ryang Kim
Keywords
Related Articles
- EP ID EP150396
- DOI -
- Views 84
- Downloads 0
Protective effect of non-selective and selective COX-2-inhibitors in acute immobilization stress-induced behavioral and biochemical alterations.
Acute stress has been known to produce several behavioral, neurochemical and biochemical alterations. Cyclooxygenase (COX) enzymes are involved in pathogenesis of several brain disorders including Alzheimer disease, epil...
Mebeverine influences sodium ion transport in the distal colon.
The study was performed to check if the well-known intestinal spasmolytic effect of mebeverine is paralleled by any changes in intestinal transepithelial currents. The transepithelial potential difference related to ioni...
Impact of ursolic acid on chronic ethanol-induced oxidative stress in the rat heart.
Oxidative stress plays an important role as a mediator of myocardial damage produced by ethanol. This work was designed to investigate the effect of ursolic acid (UA), a reported radical scavenger and antioxidant, on oxi...
Activation of the NMDA/glutamate receptor complex antagonizes the NMDA antagonist-induced antidepressant-like effects in the forced swim test.
The antidepressant activity of NMDA receptor antagonists has been demonstrated, and their mechanism of action was based on the assumption of their selectivity for the NMDA receptor only. However, no direct evidence for t...
Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.
Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial commun...