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Purpose: The histone deacetylases (HDAC) inhibitor, valproic acid (VPA), is a common antiepileptic drug and is attractive for its broad range of therapeutic effects on many diseases. It has been employed as an inducer of pluripotency in some cultured cells. Conversely, VPA has also been employed as an inducer of in vitro differentiation in many other cells. Therefore, we employed WJMSCs as a cellular target to evaluate the differential effects of of VPA on potency state and differentiation level of Wharton's Jelly mesenchymal stem cells (WJMSCs) in various concentrations and different culture mediums. Methods: The isolated WJMSCs were cultured in DMEM (MSC medium). According to previous protocols, WJMSCs were treated with 0, 0.5 and 1 mM VPA in MSC or embryonic stem cell (ESC) medium and 2 mM VPA in neural differentiation medium. Real-time polymerase chain reaction (PCR) and western blot analysis were performed for evaluating the expression of pluripotency markers. MTT and caspase assays were also performed on VPA-treated cells. Results: The expression of pluripotency markers and the viability of the WJMSCs - determined by MTT assay - were significantly increased after 0.5 mM VPA treatment in ESC medium. A 2 mM VPA treatment in neural differentiation medium significantly diminished the expression of pluripotency markers and the viability of WJMSCs. Conclusion: According to our results, both VPA concentration and the medium context can influence VPA effects on WJMSCs. The differential effects of VPA on WJMSCs can reflect its wide range of effects in the treatment of various diseases.
RESUMO
Cerium oxide nanoparticles (CeNPs) are one of the most widely used and important nanoparticles in addition to possessing strong antioxidative properties and inhibiting free radicals. Paraoxonase-1 (PON1) is one of the enzymes that protect the body against damage caused by oxidative stress. The purpose of this study was to investigate the effect of CeNPs on the activity of PON1 as well as biomarkers of oxidative stress in the toxicity of malathion. 48 Albino Wistar male rats with weight range of 180-250 g were randomly divided into 8 groups, Group 1: healthy control, injection of normal saline, Group 2: administration by the malathion 100 mg/kg/day, Group 3: treated with CeNPs 15 mg/kg/day, Group 4: treated with CeNPs 30 mg/kg/day, Group 5: combination of malathion with dose of 100 mg/kg/day and CeNPs 15 mg/kg, Group 6: combination of malathion with dose of 100 mg/kg/day and CeNPs 30 mg/kg for 14 days and 24 h after termination of treatment period, serum and liver tissue samples were collected from all rats. Biochemical test of PON1 activity, oxidative stress biomarkers including total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), were carried out. Malathion reduced plasma TTG levels, TAC and increased LPO in malathion group. However, CeNPs increased TTG, TAC and reduced PON1 activity. Results showed that CeNPs alone had antioxidant properties while with malathion it shows different properties.
RESUMO
BACKGROUND: Malathion is an organophosphorus pesticide that commonly used in many agricultural and non-agricultural processes. Previous studies have reported the effects of melatonin on the reproductive system. Cerium dioxide nanoparticles (CeNPs) due to their antioxidative properties are promising to impact on the development of male infertility. OBJECTIVE: The aim of this study was to evaluate the effect of CeNPs on oxidative stress and sperm parameters after malathion exposure of male rats. MATERIALS AND METHODS: 36 adult male Wistar rats were divided into 6 groups (n=6/each): Control, CeNPs -treated control (15 and 30 mg/kg/day), malathion (100 mg/ kg/day), and CeNPs -treated malathion groups (15 and 30 mg/ kg/day). At the end of the study (4 wk), the sperm counts, motility, and viability in the testis of rats were measured, also lipid peroxidation, total antioxidant capacity, and total thiol groups in homogenate testis were investigated. RESULTS: Malathion significantly reduced sperm count, viability, and motility than the control rats (p<0.001). Co-treatment of malathion with CeNPs 30 mg/kg had a protective effect on sperm counts (p=0.03), motility (p=0.01), and viability (p<0.001) compare to malathion group. Also, the results showed that malathion reduced testis total anti-oxidant capacity, the total thiol group, and increased testis malondialdehyde than the control rats (p<0.001). CeNPs 30 mg/kg are increased total antioxidant capacity (p<0.001) and total thiol group (p=0.03) compared to malathion group. CeNPs at both doses (15 and 30 mg/kg) improved malondialdehyde than the malathion group (p<0.001 and p=0.01 respectively). CONCLUSION: CeNPs 30 mg/kg administered considerably restored testicular changes induced by malathion. The improvement of oxidative stress by CeNPs may be associated with increased sperm counts, motility and viability in the testis.
