Necrosis compared with apoptosis

The benzyl-substituted titanocene 3, which showed a significant higher cytotoxicity when tested in vitro against LLC-PK, was evaluated in a series of biomedical studies as well. Watson et al. tested titanocene 3 in comparison to two aryl-substituted tf .va-titanocenes on prostate cancer cells, as advanced prostate cancer is not curable up to now [37]. Therefore, it was shown that all three titanocenes induced more apoptosis (programmed cell death, in contrast to necrosis) compared with cisplatin in a dose-dependent manner. Titanocene 3 had the most significant effect on the cell cycle and apoptosis. 

The actions of chemicals that cause disease or death occur at the cellular level therefore, it is necessary to conduct an array of in vitro cell culture tests to determine cytotoxicity. The bulk absorbable material is tested also, hydrolyzed products as well as extracts are assessed. The most obvious marker of toxicity is cell death. Necrosis, as compared with normal cellular apoptosis, is characterized by cellular and organelle swelling followed by rupture. Apoptosis, in contrast, is programmed cell death, which is characterized by a reduction in cell volume and basophilic staining of the chromatin. There are three common in vitro screens for toxicity — agar, direct contact, and elution assays. 

Exposure of OK and NRK-25E cells to ochratoxin A in the presence of an inhibitor of ERK 1/2 showed that the toxicity of ochratoxin A, as measured by cell number, protein, epithelial tightness, apoptosis and necrosis, was increased. Biomarkers of inflammation, fibrosis and epithelial mesenchymal transition were also enhanced in the presence of the inhibitor of ERK 1/2, compared with ochratoxin A alone. The authors speculated that the toxicity of ochratoxin A may be influenced by the balance between the profibrotic ERK 1/2 and the antifibrotic JNK and p38, which are not affected by inhibition of ERK 1/2, and that naturally occurring inhibitors of ERK 1/2, such as anthocyanidins, may amplify the effects of ochratoxin A (Sauvant et al., 2005c). 

In mice administered a single 20 mg dose (per 28-30 g animal) of diterpenoids isolated from skullcap, an increase in hepatic caspases was observed as compared to controls. In one skullcap-treated mouse, apoptosis affected a few hepatocytes, while in two other skullcap-treated mice, necrosis affected a few hepatocytes. No adverse effects were observed in the 13 other skullcap-treated mice. No apoptosis or necrosis was observed in the control group, nor in a group administered skullcap and pretreated with a caspase inhibitor (Haouzi et al. 2000). 

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