Hydroxychloroquine attenuates sepsis-induced acute respiratory distress syndrome in rats

Abstract

Background: This study investigates the effects of hydroxychloroquine (HCQ) on a sepsis-induced acute respiratory distress syndrome (ARDS) model in rats, initiated by a fecal intraperitoneal injection procedure (FIP).

Methods: Three groups were established: control (n=8), FIP + saline (n=7), and FIP + HCQ (20 mg/kg/day) (n=9). Blood samples were collected for arterial blood gas and biochemical analyses, and bilateral pneumonectomy was performed for histopathologic examination.

Results: In the FIP + saline group, PaO2 decreased and PaCO2 increased, whereas these levels normalized in the FIP + HCQ group compared to the control (p<0.001 and p<0.05, respectively). Histopathological scores for alveolar congestion, perivascular/interstitial edema, hemorrhage in alveolar tissue, leukocyte infiltration or aggregation in air spaces/vascular walls, and alveolar wall/hyaline membrane thickness increased in the FIP + saline group compared to the control group (p<0.01). These scores decreased in the FIP + HCQ group compared to the FIP + saline group (p<0.01). HCQ reversed the sepsis-induced increase in malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and lactic acid.

Conclusion: HCQ may be an effective and safe option to mitigate the severe progression of ARDS.

Figure 1

Microscopic images of lung tissue stained with Hematoxylin and Eosin (H&E, magnification: x20 and x40). a,b: Control group, displaying normal alveolar and interstitial structure (indicated by an arrow). c,d: FIP (fecal intraperitoneal injection procedure, sepsis induced) + saline group, showing leukocyte infiltration in air spaces and vessel walls (marked with*) and perivascular/interstitial edema (indicated by an arrow). e&f: FIP + 10 mg/kg hydroxychloroquine (HCQ) group, demonstrating reduced leukocyte infiltration and interstitial edema (indicated by an arrow).