Therapeutic effects of treatment with combination of methylprednisolone and cyclosporine-A on paraquat poisoning

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Journal Title:
CHINESE JOURNAL OF EMERGENCY MEDICINE
Issue:
Volume 19, Issue 04, 2010
DOI:
10.3760/cma.j.issn.1671-0282.2010.04.005
Key Word:
Paraquat;Poisonging;Pulmonary fibrosis;Methylprednisolone;Cyclosporine A;Pathological changes in pulmonary tissue;Indexes of oxidation-antioxidation;Specific indexes of pulmonary fibrosis

Abstract: Objective To explore the effects of early treatment with combination of high doses of methyl-prednisolone and cyclosporine-A on pathological changes of pulmonary tissue, and the specific markers of oxidation-antioxidation and pulmonary fibrosis in rats with paraquat (PQ) poisoning, and to evaluate the therapeutic effects. Method (1) Rat models of pulmonary fibrosis induced by PQ in 40 Wistar male rats were randomly divided into five groups by different doses of 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg and 40 mg/kg injected intraperi-toneally. The effective exposure dose of paraquat to establish the rat model of pulmonary fibrosis was determined by two-week mortality and pathohistological changes in pulmonary tissue and verified with biomarkers changed. (2) Observation on the therapeutic effects of treatment with combination of methylprednisolone and cyclosporine-A on rats with pulmonary fibrosis induced by paraquat was carried out. A total of 72 male Wistar rats were randomly di-vided into normal control group (n=8,25 mg/kg of 0.9% sodium chloride, i.p), model group (n= 16, 25 mg/kg of paraquat, i. p) and drug intervention group (n= 48, 25 mg/kg paraquat, i. p given in different inter-vals) . The rats in drug intervention group were further divided into three subgroups (n= 16 in each subgroup) as per the drug given 2 h, 24 and 72 h after paraquat exposure. Each rat in drug group received a single intraperi-toneal injection of methylprednisolone 90 mg/kg and cyclosporine-C 22.5 mg/kg. Seven days and 14 days after paraquat exposure, pathological changes in the pulmonary tissue were observed, and the contents of superoxide dis-mutase (SOD), malondialdehyde (MDA) and hydroxyproline (HPY) in pulmonary tissue were assayed by using alkali hydrolysis method, xanthinoxidase method and thiobarbituric acid method, retrospectively. Comparisons be-tween groups was performed with two-factor factorial design analysis of variance and intra-group comparisons were performed with three levels of single-factor analysis of variance. Results The effective exposure dose of paraquat was 25 mg/kg potent enough to produce a rat model of pulmonary fibrosis. Compared with model group, the rats in drug intervention group exhibited more intact pulmonary alveoli, slighter fibroblast proliferation and less content of collagen and fiber. In the pulmonary tissue of rats in all drug intervention groups, the content of SOD increased and the content of both HPY and MDA decreased significantly (P < 0.05 or P <0.01). Compared with 72 h drug intervention group, the fibroblast proliferation in both 2 h and 24 h drug intervention groups was slighter, the contents of both collagen and fiber were lesser, and the levels of SOD in pulmonary tissue increased significantly (P <0.05orP <0.01), but the levels of MDA decreased significantly (P< 0.01). Conclusions Early treat-ment for paraquat-poisoned rats with the combination of the high dose of methylprednisolone and cyclosporine-C can significantly reduce the oxidative injury of pulmonary tissue and the magnitude of pulmonary fibrosis, improving the outcome of the rats.

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