title: [Study on the therapeutic effects of tetrandrine combined with N-acetylcysteine on experimental silicosis of rats].
abstract: OBJECTIVE
  To compare the effects of oral treatment with tetrandrine (TD) and N-acetylcys-teine (NAC) separately or jointly on silica-exposed rats.
  
  
  METHODS
  40 sprague-Dawly (SD) rats were randomly divided into normal saline group, quartz group, TD treatment group (50 mg/kg), NAC treatment group (500 mg/kg) and combined treatment group (TD: 50 mg/kg + NAC: 500 mg/kg). Rats in normal saline group and other groups received intratracheal instillation of normal saline and quartz dust suspension respectively. Treatment groups were given TD, NAC separately or jointly via esophagus the next day after instillation, once a day and six times a week for 30 consecutive days. At the end of experiment, the pathological changes of lung tissues were evaluated by the methods of Foot, HE and Masson staining, the level of hydroxyproline (HYP), malondjalde-hyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lung tissues were measured by alkaline hydrolysis method, the barbituric acid method and enzyme-linked immunosorbent assay (ELISA) respectively.
  
  
  RESULTS
  Compared with the quartz group, lymph nodes/body coefficients in all treatment groups and lung/body coefficient in combined treatment group were significantly decreased (P < 0.05). Pathology results showed that the normal saline group demonstrated no obvious evidence of lung damage. The quartz group lungs silicotic lesions focused on II~III level, the TD treatment group was mainly with I level, the NAC treatment group was mainly with I~II level, and the combined treatment group only showed little silicotic nodule, no obvious fibrosis. HYP content in TD treatment group and combined treatment group were significantly lower than that in the quartz group (P < 0.05), while it showed no obvious change in NAC treatment group. MDA content in lung tissues of each treatment group (TD treatment group, NAC treatment group and combined treatment group) were 18.80 ± 2.94, 20.13 ± 4.01 and 17.05 ± 3.52 nmol/ml respectively, which lower than in the quartz group (23.99 ± 3.26 nmol/ml). The level of IL-6 in lung tissues of the quartz group were 89.57 ± 8.78 pg/ml. After TD and NAC monotherapy, the IL-6 content decreased to 79.22 ± 9.65 pg/ml and 81.63 ± 5.72 pg/ml, and it decreased more significantly after combined medication (74.37 ± 3.17 pg/ml). The level of TNF-α in the quartz group were 59.05 ± 4.48 pg/ml. After TD and NAC monotherapy, the TNF-α content decreased to 50.48 ± 2.76 pg/ml and 54.28 ± 4.30 pg/ml, and it decreased more significantly after combined medication (49.10 ± 4.98 pg/ml).
  
  
  CONCLUSIONS
  NAC and TD could reduce MDA, TNF-α and IL-6 levels in lung tissue, and alleviate SiO2-induced pulmonary fibrosis in rats. Combined treatment with TD and NAC was more effective than TD or NAC treatment separately.
authors.affiliation: Institute of Occupational Disease Prevention, Zhejiang Academy of Medical Sciences Hangzhou, Zhejiang 310013, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Hailing
authors.initials: H
authors.lastname: Xia
authors.forename: Lijin
authors.initials: L
authors.lastname: Zhu
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Li
authors.forename: Riping
authors.initials: R
authors.lastname: Chen
authors.forename: Xianhong
authors.initials: X
authors.lastname: Yin
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Jiang
authors.forename: Lingfang
authors.initials: L
authors.lastname: Feng
authors.forename: Junqiang
authors.initials: J
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Jianlin
authors.initials: J
authors.lastname: Lou
authors.affiliation: E-mail: xingtyou@mail.hz.zj.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004391:Dust; D006909:Hydroxyproline / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D011791:Quartz / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D004391:Dust; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011791:Quartz; C009438:tetrandrine; D008315:Malondialdehyde; D012822:Silicon Dioxide; D006909:Hydroxyproline; D000111:Acetylcysteine