Abstract:
:4-hydroxynonenal (4-HNE) and 6-hydroxydopamine (6-OHDA)-mediated damage in dopaminergic neurons is well documented. Protective potential of steroidal hormone (17β-estradiol) has also been suggested. However, therapeutic potential of such promising hormone is hampered due to complex brain anatomy and physiology. Thus, the present investigations were studied to suggest the applicability of dopamine expressing PC12 cells as in vitro tool to screen the pharmacological potential of 17β-estradiol against 4-HNE and 6-OHDA. MTT assay was conducted for cytotoxicity assessment of both 4-HNE (1 μM to 50 μM) and 6-OHDA (10(-4) to 10(-7) M). Non-cytotoxic concentrations, that is, 4-HNE (1 μM) and 6-OHDA (10(-6) M) were selected to study the synergetic/additive responses. PC12 cells were found to be more vulnerable towards co-exposure of individual exposure of 4-HNE and 6-OHDA, even at non-cytotoxic concentrations. Then, cells were subjected to pre-treatment (24 hours) of 17β-estradiol (1 μM), followed by a permutation of combinations of both 4-HNE and 6-OHDA. Pretreatment of 17β-estradiol was found to be significantly effective against the cytotoxic responses of 4-HNE and 6-OHDA, when the damage was at lower level. However, 17β-estradiol was found to be ineffective against higher concentrations. Physiological-specific responses of PC12 cells against 4-HNE/6-OHDA and 17β-estradiol suggest its applicability as first tier of screening tool.
journal_name
Hum Exp Toxicoljournal_title
Human & experimental toxicologyauthors
Siddiqui MA,Kashyap MP,Al-Khedhairy AA,Musarrat J,Khanna VK,Yadav S,Pant ABdoi
10.1177/0960327110382130subject
Has Abstractpub_date
2011-08-01 00:00:00pages
860-9issue
8eissn
0960-3271issn
1477-0903pii
0960327110382130journal_volume
30pub_type
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