Bleomycin induces molecular and structural changes in rat liver with androgen deficiency

EGGEL ML; BIAGGIO VS; GOMEZ NN; CIMINARI E; PEREZ CHACA MV

San Luis

Congreso; XXXIX Sociedad de Biología de Cuyo; 2021

XXXIX Sociedad de Biología de Cuyo

Bleomycin (BLE) is an anti-neoplastic agent used as first-line therapy in many human cancers treatment; also is used in many experimental model because it induces pulmonary fibrosis. Testosterone deficiency generate morphological and biochemical alterations in lung, increasing oxidant molecules which lead to redox imbalance. Our goal is dilucidated molecular and biochemical changes produced by BLE in rat lungs with androgen deficiency (AD). Present study used Wistar male control and castrated rats (200 ±20 gr) administered with two different BLE doses (BLE1 0.15 mg/kg and BLE2 10 mg/kg): 1) control (Co); 2) Co+BLE1; 3) Co + BLE2; 4) Ca (castrated); 5) Ca+BLE1 and 6) Ca+BLE2. After 40 days of treatment, rats were sacrificed. Malondialdehyde (MDA) content was determined and Co+BLE2 (p<0.001), Ca (p<0.01) Ca+BLE2 (p<0.0001) and Ca+BLE1 (p<0.05) increased significantly with respect to Co. Also antioxidant enzymes activity were measured like catalase (CAT) activity which rise significantly in Co+BLE1, Co+BLE2, Ca, Ca+BLE1 y Ca+BLE2 compared with Co (p <0.0001) while Ca+BLE2 (p<0,001) and Co+BLE1 (p<0,0001) decreased significantly regarding to Ca. Superoxide dismutase (SOD) expression augmented significantly in Co+BLE2 (p<0,001), Ca+BLE1 (p<0,0001) with respect to Co whereas increased significantly in Co+Bleo 1, Co+Bleo 2 y Ca+Bleo 1 (p<0,0001) in relation to Ca. At the same time diminished significantly in Ca and Ca+BLE2 compared to Co (p<0.0001). Antioxidant Glutathione Peroxidase (GPx) gene expression decreased in Ca and Ca+BLE2 (p<0, 0001) with respect to Co, although it rises (p<0.0001) Ca+BLE1 compared to Co. Finally in all treated BLE groups, GPx increased significantly in relation to Ca (p<0.0001). We can conclude that in lung lower Bleomycin dose (BLE1) activate antioxidant defense system where enzymes can respond adequately, while a higher Bleomycin concentration (BLE2), increased ROS levels by lipoperoxidation, at which point antioxidant defense system is not enough to face oxidative stress. Likewise state descripted is exacerbated by androgen deprivation.