ABSTRACT
A common side effect to cytotoxic antibiotic bleomycin [BLM] is interstitial pneumonitis with progressive pulmonary fibrosis. At the same time, some of the angiotensin renin system [RAS] inhibitors are reported to have anti-inflammatory in addition to their antihypertensive effects. This study investigated the potential anti-inflammatory effect of angiotensin converting enzyme inhibitors captopril and enalapril and angiotensin receptor blockers losartan and candesartan on experimental BLM-induced acute lung injury in rats. BLM-induced lung injury was assessed by the total white cell count, neutrophil count and interleukin-8 [IL-8] in bronchoalveolar lavage [BAL] fluid and serum level of tumor necrosis factor-alpha [TNF- alpha]. In addition, oxidative stress in lung tissue was measured by tissue contents of malondialdehyde [MDA] and reduced glutathione [GSH], enzymatic activity of superoxide dismutase [SOD] and catalase [CAT] in lung homogenate. A single intravenous dose of BLM was given on day 14[th] of the study. The four investigated RAS inhibitors [Captopril, enalapril, losartan and candesartan] were examined in two different regimens. The first regimen [a] was to start the RAS inhibitor on day 14[th] of the study with BLM and to continue for one week after BLM. In the second regimen [b], the RAS was started 2 weeks prior to BLM and continued for one week thereafter. Administration of candesartan was accompanied with significant decrease in the total white cell and neutrophil counts. Further, significantly lower counts were found when the drug was started two weeks prior to induction of BLM-lung injury [regimen b] compared to its introduction with BLM on day 14[th] [regimen a] [p<0.001]. The associated lower level of IL-8 in BAL in all RAS inhibitors groups failed to reach level of statistical significance compared to BLM control injury [p>0.05]. However, the level of TNF-alpha in serum was decreased significantly in all RAS inhibitors-treated groups. Significant higher lung tissue content of GSH with all RAS treated groups - especially with captopril, there was a significant difference between regimen a and b- compared to BLM-injury control group. There was a significant lower activation of SOD and CAT and less MDA content with all RAS inhibitors treated groups than BLM-injury control group [p<0.001]. All the investigated drugs exhibited significant anti-inflammatory and antioxidant effect especially the prophylactic regimen with captopril. Candesartan was the only drug that affects the macrophage mobility and its chemotactic activity