Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods 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. Results 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, NO.O1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

The Bidirectional Effects of Arsenic on miRNA-21: A Systematic Review and Meta-analysis

Objective Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer. Methods We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21. Results Low-dose arsenic exposure（≤ 5 μmol/L） can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3（pSTAT3） expression, and decrease programmed cell death protein 4（PDCD4） and protein sprouty homolog 1（Spry1） expression. High-dose arsenic exposure（〉 5 μmol/L）, can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure（≤ 24 h） can increase miRNA-21 and pS TAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure（〉 24 h） can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes. Conclusion Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.

Grape Seed Procyanidin Extract Reduces Arsenic- Induced Renal Inflammatory Injury in Male Mice

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）-KB 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-KB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.