Correlation between urinary KIM-1 and kidney protein expression of p-ERK following damage in rats exposed to gentamicin or lead acetate.

Kidney injury molecule-1 (KIM-1) is a membrane receptor upregulated in the proximal tubule cells following various types of kidney injuries. Notably, studies have suggested a correlation between KIM-1 expression and extracellular signal-regulated kinase (ERK) activation. In this study, we aimed to investigate the association between the kidney overexpression pattern of cytoplasmic phosphorylated-ERK (p-ERK) protein and increased urinary KIM-1 levels in rats exposed to gentamicin or lead acetate, both at the end of toxic exposure and after a 4-week recovery period. Although other proteins were evaluated, only kidney overexpression of cytoplasmic p-ERK protein correlated with increased urinary KIM-1 levels. For both toxic substances, the increased urinary KIM-1 levels corresponded with kidney inflammation. Our results suggest that KIM-1 and p-ERK share a common mechanism in kidney injury mediated by both toxic substances that induce proximal tubule damage.

Oral Administration of Microencapsulated B. Longum BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model.

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (Bifidobacterium longum, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and ß-glucuronidase (ß-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.

Anticarcinogenic Effect of Corn Tortilla Against 1,2-Dimethylhydrazine (DMH)-Induced Colon Carcinogenesis in Sprague-Dawley Rats.

Mexico has the highest per capita consumption of corn in the world, which is consumed mainly as tortilla. However, only a few in vivo studies have demonstrated the anticarcinogenic potential of some maize components against colon cancer, but not as a whole food product. Therefore, our objective was to evaluate the protective effect of corn tortillas against the development of colon cancer. First, blue, red, yellow and white corn grains were lime-cooked and processed to elaborate tortillas. Then, tortillas were administered into the diet (27% w/w) to male Sprague-Dawley rats induced with the colon carcinogen 1,2-dimethylhydrazine (DMH). Our results indicated that consumption of tortillas, particularly from white and blue corns, significantly decreased adenocarcinoma incidence (up to 77.5%) and mean number compared to DMH-treated animals. In addition, an inhibition of ß-glucuronidase activity, and induction of detoxifying enzymes in liver and colon, as well as a decrease in the expression of the two most important proliferative proteins (K-ras and ß-catenin) involved in colon carcinogenesis, were also observed. These results highlight some of the molecular mechanisms related to the chemopreventive effect of tortillas, thus indicating that corn products retain their biological properties even after nixtamalization and tortilla processing.

Transcriptomic analysis in diabetic nephropathy of streptozotocin-induced diabetic rats.

Diabetic nephropathy (DN) is a major complication of diabetes and is caused by an imbalance in the expression of certain genes that activate or inhibit vital cellular functions of kidney. Despite several recent advances, the pathogenesis of DN remains far from clear, suggesting the need to carry out studies identifying molecular aspects, such as gene expression, that could play a key role in the development of DN. There are several techniques to analyze transcriptome in living organisms. In this study, the suppression subtractive hybridization (SSH) method was used to generate up- and down-regulated subtracted cDNA libraries in the kidney of streptozotocin (STZ)-induced diabetic rats. Northern-blot analysis was used to confirm differential expression ratios from the obtained SSH clones to identify genes related to DN. 400 unique SSH clones were randomly chosen from the two subtraction libraries (200 of each) and verified as differentially expressed. According to blast screening and functional annotation, 20.2% and 20.9% of genes were related to metabolism proteins, 9% and 3.6% to transporters and channels, 16% and 6.3% to transcription factors, 19% and 17.2% to hypothetical proteins, and finally 24.1 and 17.2% to unknown genes, from the down- and up-regulated libraries, respectively. The down- and up-regulated cDNA libraries differentially expressed in the kidney of STZ diabetic rats have been successfully constructed and some identified genes could be highly important in DN.

Long-term toxicological effects of persistent luminescence nanoparticles after intravenous injection in mice.

The ZnGa1.995Cr0.005O4 persistent luminescence nanoparticles offer the promise of revolutionary tools for biological imaging with applications such as cell tracking or tumor detection. They can be re-excited through living tissues by visible photons, allowing observations without any time constraints and avoiding the undesirable auto-fluorescence signals observed when fluorescent probes are used. Despite all these advantages, their uses demand extensive toxicological evaluation and control. With this purpose, mice were injected with a single intravenous administration of hydroxylated or PEGylated persistent luminescence nanoparticles at different concentrations and then a set of standard tests were carried out 1day, 1 month and 6 months after the administration. High concentrations of hydroxylated nanoparticles generate structural alterations at histology level, endoplasmic reticulum damage and oxidative stress in liver, as well as rising in white blood cells counts. A mechanism involving the endoplasmic reticulum damage could be the responsible of the observed injuries in case of ZGO-OH. On the contrary, no toxicological effects related to PEGylated nanoprobes treatment were noted during our in vivo experiments, denoting the protective effect of PEG-functionalization and thereby, their potential as biocompatible in vivo diagnostic probes.

Lycopene Improves Diet-Mediated Recuperation in Rat Model of Nonalcoholic Fatty Liver Disease.

The aim of the present study was to evaluate the synergic effect of lycopene (LYC) treatment with a dietary control in a nonalcoholic fatty liver disease (NAFLD) model induced with a high-fat diet (HFD). Sprague-Dawley rats were fed during 4 weeks with a normal diet (ND·4w) or an HFD (HFD·4w) to produce an NAFLD model. Then, rats from the ND·4w group continued during 4 weeks with the same diet (ND·8w), and rats from HFD were fed during 4 weeks with an ND (HFD·4w+ND·4w) or an ND plus LYC (HFD·4w+ND+LYC·4w). LYC (20 mg/kg) was administered daily by gavage. ND and ND+LYC diets partially reverted the following alterations due to HFD: liver weight, serum low-density lipoproteins (LDL), hepatic total cholesterol (TC), and catalytic activity of hepatic superoxide dismutase, catalase, and glutathione peroxidase, as well as macroscopic and microscopic images of livers. A higher recuperation to reach normality was obtained with ND+LYC in: liver weight, hepatic TC, serum LDL, and, in some instances, macroscopic and microscopic images of livers. Failures to recovery with both NDs were observed for malondialdehyde level and serum aspartate aminotransferase activity. Taken together, the results from this study suggest the potentially protective role of LYC against NAFLD; however, more clinical trials are needed to support this idea.

Salicylic acid elicitation during cultivation of the peppermint plant improves anti-diabetic effects of its infusions.

Peppermint (Mentha piperita) infusions represent an important source of bioactive compounds with health benefits, which can be enhanced by applying salicylic acid (SA) during plant cultivation. The aim of this study was to evaluate the effect of SA (0, 0.5 and 2 mM) during peppermint cultivation on the chemical profile of saponins and alkaloids, as well as the anti-diabetic properties of the resulting infusions. The results showed that a 2 mM SA treatment significantly improved the chemical profiles of the infusions. Furthermore, the administration of 2 mM SA-treated peppermint infusions for 4 weeks to a high-fat diet/streptozotocin-induced diabetic rats decreased serum glucose levels (up to 25%) and increased serum insulin levels (up to 75%) as compared with the diabetic control. This can be related to the observed protection on pancreatic ß-cells. Furthermore, 0.5 and 2 mM SA-treated peppermint infusions decreased LDL (24 and 47%, respectively) and increased HDL levels (18 and 37%, respectively). In addition, all groups treated with peppermint infusions had lower serum and liver triglyceride contents, where 2 mM SA peppermint infusion showed the highest effect (44% and 56%, respectively). This is probably caused by its higher capacity to inhibit pancreatic lipase activity and lipid absorption. Moreover, SA-treated peppermint infusions improved the steatosis score in diabetic rat liver and decreased serum transaminase levels, probably as a result of the increase in steroidal saponins and alkaloids, such as trigonellin. Therefore, the application of 2 mM SA during cultivation of peppermint could be used to improve the anti-diabetic properties of peppermint infusions.

Antioxidant, anti-inflammatory and anticarcinogenic activities of edible red oak (Quercus spp.) infusions in rat colon carcinogenesis induced by 1,2-dimethylhydrazine.

Red oak (Quercus spp.) leaves are traditionally used as food in Mexico, and some of their infusions have potential anticarcinogenic and anti-inflammatory effects; however, these properties have not yet been scientifically tested. The aim of this work was to explore the anti-inflammatory activity in HT-29 cells and anticarcinogenic effect in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis of red oak infusions. Quercus infusions were prepared and administered as the sole source of drink to male Sprague-Dawley rats (1% w/v) for the entire 26-week experimental period. On week 4, rats received 8 subcutaneous injections of DMH (21 mg/kg body weight) once a week. The results showed that mean tumor (0.9 ± 0.2 vs. 2.6 ± 0.3) and multiplicity (1.2 ± 0.1 vs. 2.0 ± 0.23), and ß-catenin protein level (2.2-fold) in adenocarcinomas were significantly lower in Quercus sideroxyla-treated group compared with DMH group. By contrast, Quercus durifolia and Quercus eduardii infusions had no protective effect. Additionally, the experiments in HT-29 cells confirmed that Q. sideroxyla infusion effectively decreased the levels of the inflammatory markers COX-2 and IL-8 by modulating the expression of NF-κB. These results highlight some of the molecular mechanisms related to the chemopreventive effect of Q. sideroxyla infusion and its potential value as a source of bioactive compounds.