ABSTRACT
The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.
Subject(s)
Animals , Male , Mice , Arsenic , Toxicity , Grape Seed Extract , Therapeutic Uses , Inflammation , Drug Therapy , Kidney Diseases , Drug Therapy , Proanthocyanidins , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity.</p><p><b>METHODS</b>Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed.</p><p><b>RESULTS</b>ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST.</p><p><b>CONCLUSION</b>GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.</p>