Alteration of Diazinon-Induced pmaip1, gstm1, cyp1a1, and diras3 Gene Expression Levels in MRC-5/Human Lung Fibroblast Cell Line by Sambucus ebulus (L)

Abstract

Background: Diazinon is an organophosphorus pesticide extensively used to control pests. Although much evidence suggests that diazinon may have toxic effects in humans, it is still used in large amounts in many countries. Objectives: The current study investigated the effect of diazinon on human lung fibroblast cell line (MRC-5) and the possible protective effect of Sambucus ebulus methanol leaf extract. Methods: We treated MRC-5 cells with 5, 10, 25, 50, and 100 μM concentrations of diazinon and analyzed the expression levels of two genes from phase I and phase II detoxification (cyp1a1 and gstm1, respectively) and two DNA damage sensor and apoptosis marker genes (pmaip1 and diras3, respectively) in treated cells. Furthermore, the effects of 5, 10, 20, 40, and 80 μg/mL of the extract in combination with 50 μM of diazinon were investigated on the mRNA levels of the selected genes in MRC-5 cells. Results: Diazinon could strongly upregulate cyp1a1 and diras3. The diazinon concentrations of less than 100 μM significantly induced gstm1 and pmaip1 expression in treated cells compared to controls. The mixture of diazinon and extract dramatically downregulated gstm1 and pmaip1 expression in treated cells but strongly elevated the mRNA levels of diras3 and slightly induced cyp1a1 expression in MRC-5 cells. Conclusions: Based on the study, exposure to high concentrations of diazinon may induce DNA damage and apoptosis. In addition, S. ebulus extract had a high potential for free radical scavenging; however, the genotoxic effects of the extract were also observed.