Molecular and cellular effects of vitamin B12 forms on human trophoblast cells in presence of excessive folate.
Folic acid (FA) and iron are essential supplements during pregnancy. Similarly effects of vitamin B12 (B12) inadequacy and high folate and low B12 status, on pregnancy outcome are available. However there are no mandatory recommendations for B12. There are many forms of B12 viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl), and Hydroxycobalamin (HCbl) though there is limited consensus on which form has better efficacy. In the present study we have determined effect of various forms of B12 in the presence of two FA concentrations namely normal physiological (20ng/mL; NPFA) and supra-physiological (2000ng/mL; SPFA) concentration to mimic real time situation where FA is in excess due to supplementation. We assessed trophoblastic proliferation, viability, TNFα and EGFr mRNA expression, homocysteine, β-hCG and MDA levels. Trophoblastic viability was significantly suppressed at SPFA concentration and was restored by B12 treatment with Cbl, AdCbl and combination of MeCbl+AdCbl. The mRNA expressions of TNFα were up-regulated, while EGFr were down-regulated at SPFA concentrations, as validated by RT-PCR. Treatment with MeCbl+AdCbl significantly decreased homocysteine and MDA levels at SPFA concentrations. High levels of FA alone had a detrimental effect on placental health and functions as reflected by decreased viability, EGFr expression and increased TNFα expression, homocysteine and MDA levels. Combination of B12 active forms i.e. MeCbl+AdCbl was found to be most effective in neutralising excess folate effect in-vitro.
Dr. Prabhakar Kore Basic Science Research Centre, KLE University, Nehru Nagar, Belagavi 590010, Karnataka, India.
Tejas
T
Shah
Department of Biotechnology, Sinhgad College of Engineering, Vadgaon Budruk, Pune 411041, Maharashtra, India. Electronic address: joshikalpana@gmail.com.
Kalpana
K
Joshi
Dr. Prabhakar Kore Basic Science Research Centre, KLE University, Nehru Nagar, Belagavi 590010, Karnataka, India.
Sanjay
S
Mishra
Department of Gynaecology, KEM Hospital, Rasta Peth, Pune 411041, Maharashtra, India.
Suhas
S
Otiv
Dr. Prabhakar Kore Basic Science Research Centre, KLE University, Nehru Nagar, Belagavi 590010, Karnataka, India.
Vijay
V
Kumbar
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism; D003038:Cobamides / Q000494:pharmacology*; D019610:Cytoprotection; D019587:Dietary Supplements / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000494:pharmacology* / Q000633:toxicity; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D006879:Hydroxocobalamin / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism; D011247:Pregnancy; D020011:Protective Agents / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
D018997:Chorionic Gonadotropin, beta Subunit, Human; D003038:Cobamides; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine; D008315:Malondialdehyde; D005492:Folic Acid; C019476:mecobalamin; C512478:EGFR protein, human; D066246:ErbB Receptors; C000913:cobamamide; D014805:Vitamin B 12; D006879:Hydroxocobalamin
Adenosylcobalamin; Folic acid; Gene expression; Methylcobalamin; Placenta; Vitamin B12