title: BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro.
abstract: OBJECTIVE
  The study was conducted to observe whether brain-derived neurotrophic factor (BDNF) has cytoprotective actions against alloxan (AL), streptozotocin (STZ), doxorubicin (DB) and benzo(a)pyrene (BP) compounds in vitro that may account for its beneficial action in diabetes mellitus.
  
  
  METHODS
  This in vitro study was performed using rat insulinoma (RIN5F) cells. Possible cytoprotective action of BDNF (using pre-treatment, simultaneous and post-treatment schedules of RIN5F cells with BDNF) against the four chemicals tested was evaluated using MTT and apoptosis assays. Possible mechanism of cytoprotective action of BDNF was assessed by measuring BCl2/IKB-β/Pdx mRNA transcripts and anti-oxidant levels in RIN5F cells. Effect of alloxan, STZ, doxorubicin and BP on the production of BDNF by RIN5F cells was also studied.
  
  
  RESULTS
  Results of the present study revealed that BDNF in the doses (100ng>50ng>10ng/ml) has significant cytoprotection (P<0.001, P<0.01) on cytotoxic action of AL, STZ, DB and BP against rat insulinoma RIN5F (5×10(4) cells/100μl) cells in vitro. It was observed that AL, STZ, DB and BP inhibited BDNF production significantly (P<0.001) in a dose-dependent manner by RIN5F cells (0.5×10(6) cells/500μl) in vitro, while BDNF not only prevented apoptosis induced by these four chemicals but also significantly increased (P<0.001) BCl2/IKB-β/Pdx mRNA transcripts and restored anti-oxidant levels (P<0.01) in RIN5F cells to normal.
  
  
  CONCLUSIONS
  These results suggest that BDNF has potent cytoprotective actions, restores anti-oxidant defenses to normal and thus, prevents apoptosis and preserves insulin secreting capacity of β cells. In addition, BDNF enhanced viability of RIN 5F in vitro. Thus, BDNF not only has anti-diabetic actions but also preserves pancreatic β cells integrity and enhances their viability. These results imply that BDNF functions as an endogenous cytoprotective molecule that may explain its beneficial actions in some neurological conditions as well.
authors.affiliation: BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India.
authors.forename: Siresha
authors.initials: S
authors.lastname: Bathina
authors.affiliation: National Institute of Pharmaceutical Education and Research, Hyderabad, India.
authors.forename: Nanduri
authors.initials: N
authors.lastname: Srinivas
authors.affiliation: BioScience Research Centre, Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India; UND Life Sciences, 2020 S 360th St, #K-202, Federal Way, WA 98003, USA.
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
mesh_terms: D000496:Alloxan / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000633:toxicity; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity; D004351:Drug Resistance; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D011042:Poisons / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013311:Streptozocin / Q000037:antagonists & inhibitors* / Q000633:toxicity
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007328:Insulin; D011042:Poisons; D011994:Recombinant Proteins; D001564:Benzo(a)pyrene; D013311:Streptozocin; D000496:Alloxan; C579455:BDNF protein, human; D004317:Doxorubicin
keywords: Anti-oxidants; Apoptosis; Brain-derived neurotrophic factor; Free radicals; RIN5F cells