ABSTRACT. Isoflurane can induce widespread cytotoxicity. We hypothesized that isoflurane induces apoptosis partly by causing excessive calcium release from the endoplasmic reticulum (ER) via direct activation of inositol 1,4,5-trisphosphate receptors (IP 3 R). Rat pheochromocytoma cells cultured for seven days with nerve growth factor were divided into four groups: control group (C), IP 3 R antagonist group (X), isoflurane group (I) and isoflurane + IP 3 R antagonist group (I+X). Groups I and I+X were treated with 1 MAC isoflurane for 12 h. Groups X and I+X were pretreated with IP 3 R antagonist. Annexin V/PI apoptosis and TUNEL assays were performed to evaluate cell apoptosis. TEM was used to observe changes in cell ultrastructure. Changes in ] i increased in groups I and I+X (P < 0.05). Compared to group C, IP 3 R mRNA expression was lower in group X and higher in group I (P < 0.05). Compared to group X, cell apoptosis rate, [Ca 2+ ] i and IP 3 R mRNA expression increased in groups I and I+X (P < 0.05). Compared to group I, cell apoptosis rate, [Ca 2+ ] i and IP 3 R mRNA expression decreased in group I+X (P < 0.05). These results suggest that exposure to 1 MAC isoflurane for 12 h causes excessive calcium release partly by direct activation of IP 3 R on the ER membrane and triggers cell apoptosis.

ABSTRACT. We studied the activity of matrix metalloproteinases (MMP) 2 and 9 generated by cultured rabbit corneal epithelium cells that had been stimulated with tumor necrosis factor alpha (TNF-a), to investigate the possible regulative mechanisms of MMP-2/9 and their potential effect on corneal inflammatory diseases. The rabbit corneal epithelium cells were cultured in vitro and incubated with different concentrations of TNF-a (0, 1, 10, and 100 ng/mL) for 24 h. The activity of MMP-2/9 was examined using gelatin zymography. The results were analyzed by computer image analysis and statistical tests. TNF-a stimulated the secretion of MMP-2/9 in a dose-dependent manner, and MMP-2 was activated by TNF-a. Inflammatory factors such as TNF-a can stimulate MMP-2/9 activity in corneal epithelium cells. This may be a potential manipulating mechanism of MMP expression in the 6361 MMP-2/9 in TNF-α-stimulated rabbit corneal epithelium cells ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 6360-6368 (2015) pathogenesis of corneal diseases, and could play an important role in the prevention and treatment of corneal inflammatory diseases.

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