Long term toxicity of chelerythrine on lung tissue of rats and its effect on expression of NF-κB in lung tissue / 吉林大学学报(医学版)

ABSTRACT

Objective: To observe the long-term toxicity of chelerythrine on the morphology of lung tissue and the expression level of nuclear factor-kappa B (NF-κB) in lung tissue of the rats, and to investigate the related mechanism which causing the lung tissue damage of rats. Methods: A total of 120 Wistar rats were divided into control group (given normal saline) and low (3. 7 mg middot; kg-1), moderate (5. 6 mg middot; kg-1), high (8. 4 mg middot; kg-1) dosages of chelerythrine groups (n=30). The general condition of rats in various groups was observed; HE staining was used to observe the morphology of lung tissue of the rats in various groups; the serum interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels of the rats in various groups were measured by ELISA method; real-time fluorescence quantitative PCR and Western blotting methods were used to detect the mRNA and protein levels of NF-κB and intercellular adhesion molecule-1 (ICAM-1). Results: The accumulative mortality of the rats in high dosage of chelerythrine group was the highest, followed by moderate and low dosages of chelerythrine groups. The body weights and food intakes of the rats in different dosages of chelerythrine groups were significantly lower than that in control group (P<0. 05), while the body weight and food intake of the rats in high dosage of chelerythrine group were lower than those in low and moderate dosages of chelerythrine groups (P<0. 05). Chelerythrine led to pulmonary congestion and bloody ascites of the rats. The HE staining results showed that the injuries of lung tissue in different dosages of chelerythrine groups were aggravated with the increasing of the dosage of chelerythrine. Compared with control group, the levels of IL-6, IL-8, and TNF-α in serum of the rats in different dosages of chelerythrine groups were increased significantly (P< 0.05); compared with low and moderate dosages of chelerythrine groups, the levels of IL-6, IL-8, and TNF-α in serum of the rats in high dosage of chelerythrine group were increased significantly (P<0. 05). Compared with control group, the expression levels of NF-κB and ICAM-1 mRNA and proteins in lung tissue of the the rats in different dosages of chelerythrine groups were increased significantly (P<0. 05) in a dose-dependent manner; compared with low and moderate dosages of chelerythrine groups, the expression levels of NF-κB and ICAM-1 mRNA and proteins in lung tissue of the rats in high dosage of chelerythrine group were increased (P<0. 05). Conclusion: Chelerythrine has a long-term toxic effect on lung tissue in a dose-dependent manner of the rats. Moderate and high dosages of chelerythrine may aggravate the toxic lung injury through activation of NF-κB and production of inflammatory cytokines.