Protective effect and mechanisms of pituitrin on acute paraquat-induced lung injury in rats

Abstract

To explore the protective effect of pituitrin on the development of paraquat-induced lung injury in rats. Sixty healthy Sprague Dawley female rats were randomized into 3 groups of control, paraquat and treatment (80 mg/kg, intragastric) groups (n = 20 each) Each group was divided into 4, 6, 12 and 24 h subgroups (n = 5 each). The treatment group received pituitrin, injection via internal jugular vein 30 minutes after paraquat dosing. As controls, control and paraquat groups were injected with an equal volume of saline. The paraquat content in serum and lung tissue was measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). And the levels of tumor necrosis factor-alpha (TNF-α) in sera and nuclear factor-kappa B (NF-κB) in lung tissue and the content of protein in bronchoalveolar lavage (BAL) fluid were detected at various timepoints. Lung wet-to-dry weight ratio (W/D) was recorded after pituitrin dosing. In addition, pathological changes were also observed. The highest drug concentration of paraquat in lung tissue was far lower in the treatment group than that in the paraquat group ((7.67 ± 0.91) vs (13.27 ± 0.95) µg/g, P = 0.002). There were the same result in sera ((1 695 ± 274) vs (5 377 ± 576) ng/ml, P = 0.003). The area under the concentration-time curve in the treatment group was significantly lower than that in the paraquat group (10 482 vs 43 441, P = 0.000). The levels of NF-κB in lung tissue and TNF-α in sera in the treatment group were lower than those in the paraquat group (TNF-α: 24 h: (1.85 ± 0.22) vs (2.59 ± 0.13) ng/ml, P = 0.020; NF-κB: 24 h: (88.0 ± 2.7) vs (101.8 ± 2.8) ng/g, P = 0.003). And there was a decrease in the content of protein in BAL fluid in the treatment group versus the paraquat group (BALF protein: 24 h: (125.9 ± 4.2) vs (192.7 ± 6.5)µg/ml, P = 0.003), lung W/D significantly decreased in the treatment group versus the paraquat group (12 h: 3.50 ± 0.14 vs 3.73 ± 0.15, P = 0.043; 24 h: 3.41 ± 0.06 vs 3.61 ± 0.09, P = 0.047). In addition, when compared with the paraquat group, the pituitrin-treated rats showed a mitigation of inflammatory response in lungs and reduced pulmonary edema. Pituitrin treatment decreases the content of paraquat in sera and lung homogenate in intoxicated rats and alleviates lung injury so that it may become a useful adjuvant in the treatment of acute lung injury.