In vitro and histological investigation of antitumor effect of some triazole compounds in colon cancer cell line.

1,2,4-Triazoles are used as antifungal, antibacterial, antimicrobial, and antioxidant against some oxidative radical species. Recently, many 1,2,4-triazoles continue to be synthesized. In this study, the effect of the 1,2,4-triazole derivatives on human colon cancer (HT29) was investigated in vitro and in vivo in rats. MTT test was applied to in in vitro experiments. For in vivo study, rats were divided into seven groups as follows: Control group (negative control), azoxymethane (AOM), AOM + cisplatin 15, AOM + L1, AOM + L2, AOM + L3, and AOM + L4. To create colon cancer, the AOM injection was injected subcutaneously at a dose of 15 mg/kg, three times (once weekly). The in vivo studies were completed at 28 weeks. It was found that the 1,2,4-triazole derivatives reduced the cell viability (P < 0.05). In all animals in the experimental groups, mild dysplasia was detected in 100% of the colon mucosal epithelium. Severe dysplasia and adenocarcinoma were observed in L1 groups. As a result, this study determined that the 1,2,4-triazole derivatives exhibit antitumor activity.

Combination of Soy Protein, Amylopectin, and Chromium Stimulates Muscle Protein Synthesis by Regulation of Ubiquitin-Proteasome Proteolysis Pathway after Exercise.

The present study was undertaken to investigate the effect of the combination of soy protein, amylopectin, and chromium (SAC) on muscle protein synthesis and signal transduction pathways involved in protein synthesis (mTOR pathways, IGF-1, and AktSer473) and proteolysis (FOXO1Ser256; MURF1, MAFbx) after exercise. Thirty-five Wistar rats were randomly divided into five groups: (1) control (C); (2) exercise (E); (3) exercise + soy protein (3.1 g/kg/day) (E + S); (4) exercise + soy protein + chromium (E + S + Cr); (5) exercise + soy protein + amylopectin + chromium (E + S + A + Cr). Post-exercise ingestion of SAC significantly increased the fractional rate of protein synthesis (FSR), insulin, glycogen, and amino acid levels with the highest effect observed in E + S + A + Cr group (P Ë‚ 0.05). However, SAC supplementation decreased the lactic acid concentration (P Ë‚ 0.05). A reduction in forkhead box protein O1 (FOXO1) and forkhead box protein O3 (FOXO3) (regulators of ubiquitin-related proteolysis) and muscle atrophy F-box (MAFbx) levels was noted after treatment with SAC (P < 0.05). Insulin-like growth factor 1(IGF-1) level was increased in the E + S, E + S + Cr, and E + S + A + Cr groups (P < 0.05). While the phosphorylation of 4E-BP1Thr37/46, AktSer473, mTORSer2448, and S6K1Thr389 levels increased after SAC supplementation, phosphorylated muscle ring finger 1 (MuRF-1, an E3-ubiquitin ligase gene) was found to be significantly lower compared with the E group (P Ë‚ 0.05). These results indicate that SAC supplementation improves FSR, insulin, and glycogen levels after exercise. SAC improves protein synthesis by inhibiting the ubiquitin-proteasome pathway and inducing anabolic metabolism.

Biotin and chromium histidinate improve glucose metabolism and proteins expression levels of IRS-1, PPAR-γ, and NF-κB in exercise-trained rats.

BACKGROUND: Chromium histidinate (CrHis) and biotin are micronutrients commonly used to improve health by athletes and control glycaemia by patients with diabetes. This study investigates the effects of 8-week regular exercise training in rats together with dietary CrHis and biotin supplementation on glucose, lipids and transaminases levels, as well as protein expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ), insulin receptor substrate-1 (IRS-1) and nuclear transcription factor kappa B (NF-κB). METHODS: A total of 56 male Wistar rats were randomly divided into 8 groups of 7 animals each and treated as follows: Control, CrHis, Biotin, CrHis+Biotin, Exercise, CrHis+Exercise, Biotin+Exercise, and CrHis+Biotin+Exercise. The doses of CrHis and biotin were 400 µg/kg and 6 mg/kg of diet, respectively. The training program consisted of running at 30 m/min for 30 min/day at 0% grade level, 5 days per week, once a day for 6 weeks. Serum glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL), triglycerides (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured with an automatic biochemical analyzer. Muscle and liver PPAR-γ, IRS-1 and NF-κB expressions were detected with real-time polymerase chain reaction. RESULTS: Regular exercise significantly (p < 0.001) decreased glucose, TC and TG levels, but increased HDL cholesterol. Dietary CrHis and biotin supplementation exhibited a significant (p < 0.001) decrease in glucose (effect size = large; ƞ2 = 0.773) and TG (effect size = large; ƞ2 = 0.802) levels, and increase in HDL cholesterol compared with the exercise group. No significant change in AST and ALT (effect size = none) levels was recorded in all groups (p > 0.05). CrHis/biotin improves the proteins expression levels of IRS-1, PPAR-γ, and NF-κB (effect size: large for all) in the liver and muscle of sedentary and regular exercise-trained rats (p < 0.001). CONCLUSIONS: CrHis/biotin supplementation improved serum glucose and lipid levels as well as proteins expression levels of PPAR-γ, IRS-1 and NF-κB in the liver and muscle of exercise-trained rats, with the highest efficiency when administered together. CrHis/biotin may represent an effective nutritional therapy to improve health.

The effects of Mucuna pruriens on the renal oxidative stress and transcription factors in high-fructose-fed rats.

In the present study, we evaluated the effects of M. pruriens administration on metabolic parameters, oxidative stress and kidney nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways in high-fructose fed rats. Male rats (n = 28) were divided into 4 groups as control, M. pruriens, fructose, and M. pruriens plus fructose. All rats were fed a standard diet supplemented or no supplemented with M. pruriens (200 mg/kg/d by gavage). Fructose was given in drinking water for 8 weeks. High fructose consumption led to an increase in the serum level of glucose, triglyceride, urea and renal malondialdehyde (MDA) levels. Although M. pruriens treatment reduced triglyceride and MDA levels, it did not affect other parameters. M. pruriens supplementation significantly decreased the expression of NF-Ò¡B and decreased expression of Nrf2 and HO-1 proteins in the kidney. This study showed that the adverse effects of high fructose were alleviated by M. pruriens supplementation via modulation of the expression of kidney nuclear transcription factors in rats fed high fructose diet.