Bridelia ferruginea Inhibit Rat Heart and Liver Mitochondrial Membrane Permeability Transition Pore Opening Following Myocardial Infarction

International Journal of Peptide Research and Therapeutics - Despite advances in therapy, myocardial infarction (MI) remains a leading cause of death worldwide. Recently, the mitochondrion has been...     

Modulation of adrenal cell functions by cadmium salts. 1. Cadmium chloride effects on basal and ACTH-stimulated steroidogenesis

Cultured Y-1 mouse adrenal tumor cells, which secrete 20--hydroxy-4-pregnen-3-one (20-DHP), were used to investigate the acute nonlethal effects of incremental cadmium chloride (CdCl₂) concentrations on basal and maximally stimulated steroid secretion. In addition, cumulative CdCl₂ effects during 4-hr incubations, effect reversibility, and viability were determined. Cells were incubated in 1 ml serum-free Eagle's Minimal Essential Medium (FMEM) with or without 0.5 IU (ca. 1.5 M) adrenocorticotropin (ACTH) in the presence or absence of CdCl₂. Following incubation, cell viability was quantitated using trypan blue exclusion. The 20-DHP secreted into the experimental incubation medium was measured by radioimmunoassay. CdCl₂ levels of 10.0 g/ml or greater significantly inhibited basal 30 min steroid secretion in a dose-dependent manner; ACTH-stimulated steroid secretion was significantly inhibited by levels 5.0 g/ml or greater. At least 80% of all control and stimulated cells in the presence or absence of cadmium ions excluded trypan blue. The reduction in ACTH-stimulated steroid secretion was greater than the reduction in basal steroid secretion at any cadmium concentration level. The CdCl₂ concentration that reduced stimulated steroid hormone secretion by 50% (IC₅₀) was 45.0 g/ml. Exposing Y-1 cells to either 5.0, 10.0, 45.0 or 500.0 g CdCl₂/ml FMEM for periods ranging from 0.5 to 4 hr inhibited ACTH-stimulated steroid secretion in a time-dependent manner. After 30 min exposure to 10.0, 45.0 or 500.0 g CdCl₂/ml FMEM with or without ACTH, cadmium inhibition was irreversible. When 5.0 g CdCl₂/ml was used, basal and stimulated inhibition was reversible by reincubating in medium containing ACTH alone. The relatively greater cadmium effects on ACTH stimulated steroidogenesis might suggest that cadmium modulated the rate-limited transducing system between the ACTH plasma membrane receptor complex and cholesterol side-chain cleaving mitochondrial enzymes. However, cadmium influences on basal secretion indicated effects on the non-rate-limited steroidogenic pathway.Abbreviations ACTH adrenocorticotropin - ANOVA analysis of variance - CdCl₂ cadmium chloride - Ci Curie - DNA deoxyribonucleic acid - FMEM serum-free Eagle's Minimum Essential Medium - HEPES N-2-hydroxyethylpiperazine-N-1,2-ethanesulfonic acid - IC₅₀ concentration inhibiting stimulated steroid secretion by 50% - IU international unit - MEM Eagle's Minimum Essential Medium - RIA radioimmunoassay - RNA ribonucleic acid - SEM standard error of the mean - SMEM serum-containing Eagle's Minimum Essential Medium - 20-DHP 20--hydroxy-4-pregnen-3-one