title: Bioactive 1,4-dihydroisonicotinic acid derivatives prevent oxidative damage of liver cells.
abstract: 1,4-Dihydroisonicotinic acid derivatives (1,4-DHINA) are compounds closely related to derivatives of 1,4-dihydropyridine, a well-known calcium channel antagonists. 1,4-DHINA we used were derived from a well-known antioxidant Diludin. Although some compounds have neuromodulatory or antimutagenic properties, their activity mechanisms are not well known. This study was performed to obtain data on antioxidant and bioprotective activities of: 2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydroisonicotinic acid (Ia); sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)glutamate (Ib) and sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)ethane-sulphate (Ic). 1,4-DHINA's activities were studied in comparison to Trolox by: N,N-Diphenyl-N'-picrylhydrazyl (DPPH*), deoxyribose degradation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical scavenging and antioxidative capacity assays; copper-induced lipid peroxidation of cultured rat liver cells (malondialdehyde determination by high performance liquid chromatography and 4-hydroxynonenal-protein conjugates by dot-blot); (3)H-thymidine incorporation and trypan blue assay for liver cells growth and viability. In all assays used Ia was the most potent antioxidant. Ia was also a potent antioxidant at non-toxic concentrations for liver cell cultures. It completely abolished, while Ic only slightly decreased copper-induced lipid peroxidation of liver cells. Thus, antioxidant capacities are important activity principle of Ia, which was even superior to Trolox in the cell cultures used, while activity principles of Ic and Ib remain yet to be determined.
authors.affiliation: Rudjer Boskovic Institute, Division of Molecular Medicine, Bijenicka street 54, HR-10000, Zagreb, Croatia.
authors.forename: Suzana
authors.initials: S
authors.lastname: Borovic
authors.forename: Gunars
authors.initials: G
authors.lastname: Tirzitis
authors.forename: Dace
authors.initials: D
authors.lastname: Tirzite
authors.forename: Ana
authors.initials: A
authors.lastname: Cipak
authors.forename: Gholam A
authors.initials: GA
authors.lastname: Khoschsorur
authors.forename: Georg
authors.initials: G
authors.lastname: Waeg
authors.forename: Franz
authors.initials: F
authors.lastname: Tatzber
authors.forename: Mira
authors.initials: M
authors.lastname: Scukanec-Spoljar
authors.forename: Neven
authors.initials: N
authors.lastname: Zarkovic
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D005260:Female; D007539:Isonicotinic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D007539:Isonicotinic Acids; D008315:Malondialdehyde; D003300:Copper