PMID- 2943286 OWN - NLM STAT- MEDLINE DCOM- 19860917 LR - 20190623 IS - 0006-2952 (Print) IS - 0006-2952 (Linking) VI - 35 IP - 16 DP - 1986 Aug 15 TI - Effects of cerebro-protective agents on enzyme activities of rat primary glial cultures and rat cerebral cortex. PG - 2693-702 AB - The effects of different cerebro-protective agents on selected key enzymes of the energy metabolism of rat primary glial cultures and rat cerebral cortex were studied. As indicators for the capacity of the most important pathways of energy metabolism the following enzyme activities were determined: hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-P-DH), malate dehydrogenase (MDH), glutamate dehydrogenase (GDH), and cytochrome-c-reductase (CCR). After a one week growth period, rat glial cultures were incubated for 3 or 4 weeks with the substances to be tested. Bencyclane (5 X 10(-5) mol/l) increased the activities of HK, G-6-P-DH, and LDH, whereas PFK and CCR were reduced. Pyritinol (10(-4) mol/l) led to a higher G-6-P-DH activity, simultaneously lowering the values for PFK, CCR, PK, LDH, and MDH. Under the influence of an extract of the leaves of Ginkgo bilobae (EGB; 100 mg/l) PFK, LDH, and MDH activities were reduced. All these alterations in enzyme activities went along with simultaneous reductions in protein content, therefore not allowing to exclude toxic effects with regard to the doses used. Moreover, direct interference with the analytical procedure was demonstrable for bencyclane and EGB. Piracetam (10(-3) mol/l), flunarizine (10(-6) mol/l), dihydroergocristine (5 X 10(-6) mol/l), and nicergoline (5 X 10(-6) mol/l) failed to induce any alteration in the employed doses. The most striking effects were obtained with meclofenoxate which was tested at 10(-3) and 10(-4) mol/l. The higher dose caused an elevation of HK, PFK, CCR, G-6-P-DH, GDH and MDH activities, while slightly reducing PK. With the lower dose of meclofenoxate CCR and G-6-P-DH activities were increased. Short-term incubation of the cultures with 10(-3) mol/l meclofenoxate for 24 hr led to an increase in LDH, G-6-P-DH, and GDH activities. Chronic incubation with meclofenoxate (10(-3) mol/l) followed by 48 hr deprivation of the drug resulted in elevated HK, PFK, CCR, G-6-P-DH, GDH, and MDH activities. These changes were accompanied by alterations in related metabolite levels. These include elevations in the concentration of creatine phosphate and fructose-1,6-bisphosphate, whereas glucose-6-phosphate levels were reduced. After one week of meclofenoxate deprivation the activities of CCR and G-6-P-DH were still elevated. The metabolites of meclofenoxate dimethylaminoethanol (DMAE; 10(-3) mol/l) and p-chlorophenoxyacetic acid (10(-3) mol/l) were also investigated.(ABSTRACT TRUNCATED AT 400 WORDS) FAU - Bielenberg, G W AU - Bielenberg GW FAU - Hayn, C AU - Hayn C FAU - Krieglstein, J AU - Krieglstein J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Isoenzymes) RN - 0 (Plant Extracts) RN - 2577AQ9262 (2,4-Dichlorophenoxyacetic Acid) RN - 2N6K9DRA24 (Deanol) RN - 4EMM3U5P3K (4-chlorophenoxyacetic acid) RN - 6I97Z6S135 (Bencyclane) RN - AK5Q5FZH2R (Pyrithioxin) RN - C76QQ2I0RG (Meclofenoxate) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.1.1.37 (Malate Dehydrogenase) RN - EC 1.1.1.49 (Glucosephosphate Dehydrogenase) RN - EC 1.4.1.2 (Glutamate Dehydrogenase) RN - EC 1.6.99.3 (NADH Dehydrogenase) RN - EC 2.7.1.1 (Hexokinase) RN - EC 2.7.1.11 (Phosphofructokinase-1) RN - EC 2.7.1.40 (Pyruvate Kinase) SB - IM MH - 2,4-Dichlorophenoxyacetic Acid/analogs & derivatives/pharmacology MH - Animals MH - Bencyclane/pharmacology MH - Cerebral Cortex/drug effects/*enzymology MH - Deanol/pharmacology MH - Energy Metabolism/drug effects MH - Glucosephosphate Dehydrogenase/metabolism MH - Glutamate Dehydrogenase/metabolism MH - Hexokinase/metabolism MH - Isoenzymes MH - L-Lactate Dehydrogenase/metabolism MH - Malate Dehydrogenase/metabolism MH - Male MH - Meclofenoxate/pharmacology MH - NADH Dehydrogenase/metabolism MH - Neuroglia/drug effects/*enzymology MH - Phosphofructokinase-1/metabolism MH - Plant Extracts/pharmacology MH - Pyrithioxin/pharmacology MH - Pyruvate Kinase/metabolism MH - Rats MH - Rats, Inbred Strains MH - Trees EDAT- 1986/08/15 00:00 MHDA- 2000/06/01 09:00 CRDT- 1986/08/15 00:00 PHST- 1986/08/15 00:00 [pubmed] PHST- 2000/06/01 09:00 [medline] PHST- 1986/08/15 00:00 [entrez] AID - 0006-2952(86)90177-2 [pii] AID - 10.1016/0006-2952(86)90177-2 [doi] PST - ppublish SO - Biochem Pharmacol. 1986 Aug 15;35(16):2693-702. doi: 10.1016/0006-2952(86)90177-2.