Prolonged low-dose cyclophosphamide treatment after pulse therapy attenuates lung injury in rats with paraquat intoxication

ABSTRACT

BACKGROUND/AIMS: This study tested the hypothesis that prolonged low-dose cyclophosphamide (CTX) treatment after pulse therapy attenuate paraquat (PQ)-induced lung injury in rats. METHODS: PQ (25 mg/kg) was administered intraperitoneally to induce PQ-intoxicated rat model. The rats were randomly divided into four groups control group (1 mL/day saline solution for 14 days), PQ group (1 mL/day saline solution for 14 days after PQ exposure), pulse group (15 mg/kg/day CTX in 1 mL of saline solution for 2 days and subsequent 1 mL/day saline solution for 12 days), and prolonged low-dose group (15 mg/kg/day CTX in 1 mL of saline solution for 2 days and subsequent 1.5 mg/kg/day CTX in 1 mL of saline solution for 12 days). A 14-day follow-up was conducted to determine the survival rat, and lung hydroxyproline (HYP), wet-to-dry weight ratios (W/Dc) and histopathological changes were evaluated. RESULTS: Results showed similar survival rate (55% vs. 50%, p > 0.05) between prolonged low-dose and pulse groups. Lung W/Dc (4.94 ± 0.38 vs. 5.47 ± 0.28, p < 0.01), HYP (3.34 ± 0.29 µg/mg vs. 3.65 ± 0.19 µg/mg, p < 0.001), and fibrosis score (2.69 ± 0.84 vs. 3.13 ± 0.63, p < 0.05) were lower in prolonged low-dose group than those in the pulse group. CONCLUSIONS: These findings suggested prolonged low-dose CTX treatment after pulse therapy could attenuate PQ-induced lung injury in rats.