Nebivolol attenuates acute systemic inflammation induced testicular dysfunction by decreasing transendothelial migration via VCAM-1/MMP-9 signaling

Abstract

Nebivolol (NB), which is a commonly used β₁ adrenoreceptor blocker, shows protective effects against oxidative stress and inflammation-related processes. In this study, we aimed to evaluate the possible protective effects of NB via the vascular cell adhesion molecule-1/matrix metalloproteinases-9 (VCAM-1/MMP-9) signaling pathway on systemic inflammation induced testicular dysfunction. Four groups of 32 male Wistar Albino rats were divided as (n = 8 for each) the control; lipopolysaccharide (LPS; 5 mg/kg on the third day); LPS + NB (NB: 10 mg/kg for three days and 5 mg/kg LPS 30 min following the last NB dose); NB (10 mg/kg for three days). Six hours following the LPS administration, rats were sacrificed, then testicular tissues were collected for evaluating total oxidant status (TOS), total antioxidant status and oxidative stress index (OSI) levels biochemically, VCAM-1 and MMP-9 mRNA expression levels, caspase-3 (cas-3), tumor necrosis factor-alpha (TNF-α) expressions by immunohistochemically. Systemic inflammation caused significant increases in TOS and OSI levels, VCAM-1, MMP-9, cas-3, TNF-α expressions, and a decrease of the spermatozoa count compared to the control group. NB administration successfully restored all these changes significantly. Thus, NB can be a protective drug candidate for testicular dysfunction secondary to systemic inflammation with its potent antioxidant and anti-inflammatory mechanisms.