PMID- 21125813 OWN - NLM STAT- MEDLINE DCOM- 20101230 LR - 20131121 IS - 0004-4172 (Print) IS - 0004-4172 (Linking) VI - 60 IP - 10 DP - 2010 TI - Inhibition by folic acid of tumor necrosis factor alpha and apoptosis following normothermic ischemia-reperfusion. PG - 621-6 LID - 10.1055/s-0031-1296336 [doi] AB - Folate is necessary for the production and maintenance of new cells and important during periods of rapid cell division and growth. Tumor necrosis factor-alpha (TNF-alpha) is known as a stimulant of apoptotic cell death. The present study was aimed to evaluate the efficacy of folic acid (CAS 59-30-3) in prevention of apoptosis by inhibiting TNF-alpha action in ischemia-reperfusion (I/R) induced liver injury. Eighteen Wistar rats were subjected to 1 h of hepatic ischemia followed by 3 h reperfusion and were divided into sham-operated control Group (I) (n = 6), ischemia and reperfusion group administered 0.9% saline (5 ml/kg, p.o.) for 7 days (II) (n = 6), folic acid treated group (1 mg/kg body weight/treated daily by oral route for 7 days before induced ischemia-reperfusion maneuver) (III) (n = 6). Hepatic damage in rats was assessed in terms of serum alanine transaminases and aspartate transaminases. TNF-alpha concentration was measured in serum by enzyme linked immuno assay. Necrosis and apoptosis were measured by flow cytometry and fluorescence microscopy. Apoptotic marker Bcl-2 gene expression was measured by reverse transcriptase polymerase chain reaction (RTPCR) and Western Blot Analysis. Pathological changes were measured by transmission electron microscopy (TEM). Serum alanine transaminase (ALT), aspartate transaminase (AST) and TNF-alpha concentration increased significantly (p < 0.05) in rats with I/R induced injury as compared to sham operated control rats. Pretreatment with folic acid effectively counteracted the alternation in hepatic enzymes. TEM, expression of Bcl-2 protein and flow cytometry studies confirmed the restoration of cellular normalcy and accredits the cytoprotective role of folic acid against I/R induced hepatic injury. The present study demonstrated that elevated TNF-alpha activity directly related to apoptosis and folic acid inhibits apoptosis by inhibiting the action of TNF-alpha. FAU - Chattopadhyay, Pronobesh AU - Chattopadhyay P AD - Cellular and Microbiology Laboratory, College of Pharmacy, Institute of Foreign Trade and Management, Moradabad, Uttar Pradesh, India. chatto_pronobesh@rediffmail.com FAU - Wahi, Arun Kumar AU - Wahi AK LA - eng PT - Journal Article PL - Germany TA - Arzneimittelforschung JT - Arzneimittel-Forschung JID - 0372660 RN - 0 (Tumor Necrosis Factor-alpha) RN - 935E97BOY8 (Folic Acid) RN - EC 1.1.1.49 (Glucosephosphate Dehydrogenase) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Alanine Transaminase/blood MH - Animals MH - Apoptosis/*drug effects MH - Aspartate Aminotransferases/blood MH - Blotting, Western MH - Flow Cytometry MH - Folic Acid/*pharmacology MH - Gene Expression/drug effects MH - Genes, bcl-2/drug effects MH - Glucosephosphate Dehydrogenase/metabolism MH - Hepatocytes/drug effects MH - Male MH - Microscopy, Electron, Transmission MH - Microscopy, Fluorescence MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/*pathology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/blood/*pharmacology EDAT- 2010/12/04 06:00 MHDA- 2010/12/31 06:00 CRDT- 2010/12/04 06:00 PHST- 2010/12/04 06:00 [entrez] PHST- 2010/12/04 06:00 [pubmed] PHST- 2010/12/31 06:00 [medline] AID - 10.1055/s-0031-1296336 [doi] PST - ppublish SO - Arzneimittelforschung. 2010;60(10):621-6. doi: 10.1055/s-0031-1296336.