Pharmacological doses of vitamin A increase caspase-3 activity selectively in cerebral cortex.
Vitamin A exerts a wide range of physiological roles from embryonic to adulthood stages of the mammalian life. However, there is a great concern regarding the deleterious effects of vitamin A use even therapeutically. It was shown that vitamin A induces behavioral impairments, for instance, anxiety-like behavior and depression, in experimental animals and humans. Caspases are enzymes associated with cell death; however, there is a role for such enzymes also in synaptic plasticity. Then, based on previously published data, we have investigated the effects of vitamin A supplementation at clinical doses (1000-9000 IU/kg/day) for 28 days on caspase-3 and caspase-8 activities in adult rat cerebral cortex, cerebellum, striatum, and hippocampus. Furthermore, we have quantified TNF-alpha levels, a pro-inflammatory cytokine that, besides other biological roles, trigger the extrinsic apoptotic pathway in several cellular types, in those rat brain regions. Interestingly, we found increased caspase-3 activity only in rat cerebral cortex. In all the other regions caspase-3 and caspase-8 activities did not change, as well as the levels of TNF-alpha. The presented results, herein, indicate that more caution is needed regarding vitamin A clinical use and, also importantly, the consumption of vitamin A-fortified foods, which are not exclusively distributed among vitamin A-deficient subjects.
de Oliveira
Marcos Roberto
MR
Centro de Estudos em Estresse Oxidativo, Lab 32, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Av Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil. mrobioq@yahoo.com.br
Oliveira
Max William Soares
MW
Moreira
José Cláudio Fonseca
JC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000084562:Retinyl Esters; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology
D004224:Diterpenes; D000084562:Retinyl Esters; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D014801:Vitamin A; C014794:retinol palmitate; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8