Effect of Orchidectomy on Hepatic Ischemia/Reperfusion Injury

Abstract

Abstract Background Little attention has been paid to investigate the effect of orchidectomy on hepatic ischemia/reperfusion (I/R) injury, which is lacking. The Aim of This Study is to evaluate the possible impact of orchidectomy and/or testosterone treatment on the function and structure of liver in rat model of hepatic I/R injury and, also, to explore the possible underlying mechanism(s). Materials and Methods 65 male Wistar albino-rats were divided into 5 groups; sham- operated control group (Sham), hepatic ischemia/reperfusion group (hepatic I/R), orchidectomized hepatic ischemia/reperfusion group (Orch+I/R), Testosterone- treated hepatic ischemia/reperfusion group (T+I/R) and Orchidectomized testosterone-treated hepatic ischemia/reperfusion group (Orch+T+I/R). All rats were subjected to determination of serum levels of alanine transaminase (ALT), aspartate transaminase (AST), testosterone and estradiol, and hepatic tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor- alpha (TNF-α) and gene expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Also, hepatic tissues were histopathologically assessed. Results Hepatic I/R was associated with significant rise of serum ALT and AST, and hepatic tissue TNF-α, NF-κB and MDA, and significant reduction of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2. Histopathological analysis showed vacuolization of the cytoplasm, dilated sinusoids, inflammatory cells infiltration, increased collagen fibers and significantly increased caspase-3. Hepatic I/R -mediated effects were aggravated following orchidectomy, however preischemic treatment with testosterone protected the liver as shown by the significant decline in ALT and AST, and hepatic tissue MDA, TNF-α and NF-κB, and significant enhancement of serum testosterone and estradiol, and hepatic tissue SOD and Nrf2, and restoration of hepatic architecture. Conclusion Orchidectomy hypersensitizes the liver to ischemic injury, due to exaggeration of oxidative and inflammatory states and apoptosis, while testosterone treatment improved the hepatic I/R detrimental effects on liver function and morphology due to its suppressive effect on oxidative and inflammatory states and apoptosis.