Evaluation of the hepatoprotective effects of curcumin and nanocurcumin against paraquat-induced liver injury in rats: Modulation of oxidative stress and Nrf2 pathway.

Paraquat (PQ) is a widely used herbicide all over the world, which is highly toxic for animals and humans. Its cytotoxicity is based on reactive radical generation. The aim of this study is to evaluate and compare the hepatoprotective effects of curcumin and nanocurcumin against liver damage caused by sub-acute exposure with PQ via modulation of oxidative stress and genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Rats were exposed to PQ (5 mg/kg/day, orally) + curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and serum and liver samples were collected. Next, serum enzymatic activities, liver histopathology, oxidative stress, and expression of genes involved in Nrf2 signaling pathway were assessed by biochemical and enzyme-linked immunosorbent assay methods, hematoxylin and eosin staining, and real-time polymerase chain reaction analysis. PQ significantly increased malondialdehyde, alanine transaminase, aspartate aminotransferase, alkaline phosphatase levels, and Kelch-like ECH-associated protein 1 gene expression and also decreased total antioxidant capacity, total thiol group levels, Glutathione S-transferases, heme oxygenase 1, Nrf2, and NAD(P)H:quinone oxidoreductase 1 genes expression, causing histological damages to liver tissue. These changes were significantly modulated by curcumin and nanocurcumin treatments. Our findings showed that nanocurcumin had better hepatoprotective effect than curcumin in liver damage after PQ exposure most likely through modulation of oxidative stress and genes expression of Nrf2 pathway.

Cerium and Yttrium Oxide Nanoparticles and Nano-selenium Produce Protective Effects Against H2O2-induced Oxidative Stress in Pancreatic Beta Cells by Modulating Mitochondrial Dysfunction.

BACKGROUND: Type 1 diabetes mellitus is characterized by the destruction of insulin- producing Beta cells in the pancreas. Researchers hope that islet transplantation will help to patients with insulin-dependent diabetes mellitus (IDDM). Oxidative stress is the most important challenge that beta cells face to it after isolation, and mitochondrial dysfunction is a crucial mediator in beta cells death. Hence, therapeutic approaches can shift to antioxidants through the application of nanoparticles such as cerium and yttrium oxide nanoparticles (Cer and Ytt Ox NPs) and nano-selenium (Nan Se). OBJECTIVE: This study evaluates the effects of Cer and Ytt Ox NPs and Nan Se on H2O2- induced oxidative stress in pancreatic beta cells with focus on mitochondrial dysfunction pathway. METHODS: CRI-D2 beta-cell line were pretreated with Cer Ox NPs (200 µM) + Ytt Ox NPs (0.5 µg/mL) for 3 days and/or Nan Se (0.01 µM) for 1 day. Then markers of oxidative stress, mitochondrial dysfunction, insulin and glucagon secretion were measured. RESULTS: We reported a decrease in H2O2-induced reactive oxygen species (ROS) level and glucagon secretion, and an increase in H2O2-reduced ATP/ADP ratio, MMP, as well as UCP2 protein expression, and insulin secretion by pretreatment of CRI-D2 cells with Cer and Ytt Ox NPs and/or Nan Se. CONCLUSION: We found maximum protective effect with Cer and Ytt Ox NPs on CRI-D2 beta-cell line exposed by H2O2 for keeping beta cells alive until transplant whereas combination of Cer and Ytt Ox NPs and Nan Se had very little protective effect in this condition.