Toxic effects of 70-hydroxycholesterol on rat liver primary cultures, epithelial lines and co-cultures.

Abstract

The toxic effects of 7 beta-hydroxycholesterol (7 beta-OHC) on cultures and co-cultures of rat hepatocytes, rat liver epithelial cell lines, and rat liver fibroblast lines were investigated. Hepatocytes in primary culture or co-cultured with proliferative epithelial cells, were not affected by the presence of 7 beta-OHC at a concentration of 400 microM over a period of 72 hours. In contrast, proliferative cultures of liver epithelial cell lines and liver fibroblast lines were killed by 50 microM 7 beta-OHC within the first 24 hours. Established liver epithelial cells (hyperploid) were more sensitive to 7 beta-OHC than the same line at early passages (diploid). When hepatocytes and liver epithelial cells were co-cultured and treated with 100 microM 7 beta-OHC, only epithelial cells were lysed. A concentration of 50 microM 7 beta-OHC was toxic to co-cultures of liver epithelial cell and fibroblasts together. In a serum-free medium, the cytotoxic concentration of 7 beta-OHC was lower than that in the serum-supplemented medium. Thus, liver epithelial cells cultured alone or co-cultured with hepatocytes were killed at 12.5 microM and 50 microM 7 beta-OHC, respectively. Finally, cholesterol concentrations four-fold that of 7 beta-OHC antagonized the lethal effects of 7 beta-OHC in the serum-free medium.

Comparative In Vitro Sensitivities of Human Immune Cell Lines, Vaginal and Cervical Epithelial Cell Lines, and Primary Cells to Candidate Microbicides Nonoxynol 9, C31G, and Sodium Dodecyl Sulfate

“…6 suggest that epithelial cells become less sensitive to N-9 and more sensitive to C31G with the transition from primary cell to passaged cell to immortalized cell line. Similar changes in sensitivity accompanying cellular differentiation and extensive passaging were observed in studies of 7 ␤-hydroxycholesterol cytotoxicity, in which primary rat liver epithelial cells and early-passage cells were less sensitive to 7 ␤-hydroxycholesterol than the highpassage rat liver cell line (23). Since VK2/E6E7 cells divide at a higher rate than cells in the primary (or tertiary) HVK cultures (data not shown), results observed in long-term assays, such as those illustrated in Fig.…”

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

“…Several in vitro studies demonstrated that 7β-OHC, 7KC and triol are able to induce mitochondrial dysfunction and mitochondria-dependent apoptosis [40] , [41] , [42] . We observed that such oxysterols do not affect cell viability because hepatocytes rapidly metabolize 7KC, the major dietary oxysterol [43] , [44] . However, triol significantly impaired mitochondrial respiration.…”

Toxicological profile, phytochemical analysis and anti-inflammatory properties of leaves of Vitex doniana Sweet. (Verbenaceae)

“…bw, the substance is said to be moderately toxic, and finally, if its 50% lethal dose is greater than 5000 mg/kg. bw, the substance is said to be non-toxic to health [ 26 ]. In doing so, one could then say that V. doniana extract is non-toxic.…”