Possible mechanisms involved in the protective effect of lutein against cyclosporine-induced testicular damage in rats

Oxidative stress and aberrant inflammatory response have important implications in cyclosporin-induced reproductive functions. Previous studies have shown that agents with antioxidant and anti-inflammatory activities might be beneficial in reversing cyclosporin-induced reproductive impairment. Lutein is a naturally occurring compound with antioxidant and anti-inflammatory properties. However, the effect of lutein against cyclosporin-induced reproductive impairment remains in complete. Hence, we investigated the protective effect of lutein, specifically focusing on the role of nuclear factor erythroid 2 related factor-2 (Nrf2)/heme-oxygenase-1 (HO-1)/connexin-43 (Cx-43) upregulation system against cyclosporine-induced reproductive impairment. Six male Wistar rats were allotted into 5 groups and given daily gavage of cyclosporine (40 mg/kg) and/or lutein (30 mg/kg) for four (4) weeks or in combination, respectively. The testicular antioxidant scaffolds: superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), add to sulfhydryl (T-SH), non-protein sulfhydryl (NP-SH), glutathione reductase (GR), glutathione-S -transferase (GST), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), myeloperoxidase (MPO), testicular proinflammatory cytokines, apoptotic related protein, nucleic acids, sialic acid, testicular proton pump ATPase, stress responsive protein, BTB-related protein and total protein levels in the testes were assayed thereafter. Cyclosporin significantly increased NOX-1, TNF-α, IL-1β, MPO, caspase-3 and -9 levels, which were reversed by lutein. Lutein reversed cyclosporin-induced decreases in Nrf2, HO-1, BCL-2, cytochrome C, with corresponding increase in CAT, SOD, GSH, T-SH, NP-SH, GST, GR, GSH-Px, and Cx-43 levels compared to cyclosporin groups. Lutein also abates cyclosporin-induced alterations Na + -K + -ATPase activities. Our findings showed that lutein's protective effect against cyclosporin-induced reproductive impairment might be associated with mechanisms linked to its antioxidant, anti-apoptotic, and anti-inflammatory properties, notably through up-regulation of Nrf2/HO-1/Cx-43 signaling and down-regulation of NOX-1 signaling.