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

ZELARAYAN DANIELA; ABALLAY FEDERICO; PEREZ CHACA MV; RAZZETTO G; GOMEZ NN; BIAGGIO VS; CIMINARI E

San Luis

Congreso; XXXIX Sociedad de Biología de Cuyo; 2021

XXXIX Sociedad de Biología de Cuyo

Sex is clearly a biological variable to consider in clinical research, as well as in medical practice. Testosterone deficiency is a relatively common condition and may negatively affect health and quality of life. Additionally, bleomycin (BLM) is a chemotherapeutic agent used in the treatment of different types of cancers (cytotoxic), however it generates free radicals, which induce single- and double-strand breaks in DNA. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. The present study examines potential differences in oxidative stress parameters and histological changes in control and castrated Wistar rats under two different BLM doses. Adult male rats were divided in six groups: 1) control (Co); 2) Co+BLM I (doses: 1, 5 mg/kg); 3) Co+BLM II (doses: 10 mg/kg); 4) Ca (castrated); 5) Ca+BLM I and 6) Ca+BLM II. After 40 days of treatment, rats were sacrificed. TBARS and catalase (CAT) parameters were measured and histopathological analyses of different sections of the liver from the six sample groups were also perfomed. Our results show that TBAR’S, increases in Co+ BLM II, but not significantly with respect to Co; however within androgen deficiency treatments, together with BLM administration, TBARS decrease significantly in Ca+BLM II with respect to Ca (p<0.05). CAT´s activity reacts in the same way as TBARS do in control animals. CAT activity is higher significantly in Co+BLM II vs Co and Co+BLM I (p<0.00001) and else vs all androgen deprivation treatments (p<0.0001) but no significant changes were observed between BLM different doses with androgen deficiency. Histopathology analysis showed hepatic alterations in Co+BLM; the liver has peripheral areas where hepatocytes have lipid vacuoles that increase with BLM concentration. Inside androgen deficiency, higher BLM dose exhibit liver inflammation, as well as bile ducts proliferation. Histological studies clearly demonstrated that bleomycin model induces pathological alterations in the liver producing partial systemic sclerosis. These data, although preliminary, could indicate that androgen deprivation and BLM administration induces an increase in oxidative parameters. The main changes would be that BLM produces differenteffects in control animals’ liver, with respect to androgen deficient animals liver. We can conclude that BLM responses are directly proportional to the concentration applied.