The role of glutathione in modulating organ injury in a bleomycin, etoposide and cisplatin-induced fibrosis model

Aims: The bleomycin, etoposide, and cisplatin (BEP) regimen is associated with organ fibrosis.In this study, the potential beneficial effect of the antioxidant glutathione (GSH) against BEP-induced fibrosis was investigated in a rat model.Methods: This randomized controlled study was performed on male rats, which were divided into control, BEP, or BEP+GSH groups.BEP was administered for nine weeks, and the BEP+GSH group received concomitant GSH treatment.The primary endpoints were multi-organ fibrosis and tissue injury, evaluated in the liver, lung, kidney, and skin using histopathological scoring systems.Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and urea levels were analyzed as secondary endpoints for functional organ impairment.Results: Twenty-four 12-week-old male Sprague-Dawley rats were included in this study.Histopathological fibrosis scores were significantly increased in the BEP group in comparison with the control group (Ishak score 4.00±0.00vs. 0.50±0.53,Ashcroft score 7.00±0.76vs. 1.00±1.41,renal injury score 5.50±0.53 vs. 0.00±0.00,dermal thickness 241.82±24.83 vs. 203.90±26.83µm; p<0.0001, p<0.0001, p<0.0001, p<0.05, respectively).Conversely, GSH co-administration significantly reduced tissue injury and fibrosis in the liver (1.88±0.83;p<0.0001), lungs (4.38±0.92;p<0.0001), kidneys (3.7±0.71;p<0.0001), and skin (193.64±23.70µm; p<0.01).AST levels exhibited a slight decrease in the BEP+GSH group relative to both the control (105.76±14.71U/L vs. 144.79±25.81U/L; p<0.01) and BEP groups (142.61±8.31U/L; p<0.01), yet remained within the reference range in all groups.No significant differences were observed in ALT (31.09±3.93U/L, 29.49±4.57U/L, and 33.08±4.46U/L, respectively) and urea levels (13.11±2.41mg/dL, 12.96±1.60mg/dL, and 13.20±1.98mg/dL, respectively) in control, BEP, and BEP+GSH groups.Conclusions: GSH supplementation may attenuate BEP-induced fibrosis and tissue injury in the liver, lung, kidney, and skin.