title: Protective potential of 17β-estradiol against co-exposure of 4-hydroxynonenal and 6-hydroxydopamine in PC12 cells.
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.
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: M P
authors.initials: MP
authors.lastname: Kashyap
authors.forename: A A
authors.initials: AA
authors.lastname: Al-Khedhairy
authors.forename: J
authors.initials: J
authors.lastname: Musarrat
authors.forename: V K
authors.initials: VK
authors.lastname: Khanna
authors.forename: S
authors.initials: S
authors.lastname: Yadav
authors.forename: A B
authors.initials: AB
authors.lastname: Pant
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats
chemical_list: D000447:Aldehydes; D018696:Neuroprotective Agents; D004958:Estradiol; D016627:Oxidopamine; C027576:4-hydroxy-2-nonenal