The combination of plant-derived compounds with anti-diabetic agents to manage hepatic steatosis closely associated with diabetes mellitus may be a new therapeutic approach. Silymarin, a complex of bioactive substances extracted from Silybum marianum, evinces an antioxidative, anti-inflammatory, and hepatoprotective activity. In this study, we investigated whether metformin (300 mg/kg/day for four weeks) supplemented with micronized silymarin (600 mg/kg/day) would be effective in mitigating fatty liver disturbances in a pre-diabetic model with dyslipidemia. Compared with metformin monotherapy, the metformin-silymarin combination reduced the content of neutral lipids (TAGs) and lipotoxic intermediates (DAGs). Hepatic gene expression of enzymes and transcription factors involved in lipogenesis (Scd-1, Srebp1, Pparγ, and Nr1h) and fatty acid oxidation (Pparα) were positively affected, with hepatic lipid accumulation reducing as a result. Combination therapy also positively influenced arachidonic acid metabolism, including its metabolites (14,15-EET and 20-HETE), mitigating inflammation and oxidative stress. Changes in the gene expression of cytochrome P450 enzymes, particularly Cyp4A, can improve hepatic lipid metabolism and moderate inflammation. All these effects play a significant role in ameliorating insulin resistance, a principal background of liver steatosis closely linked to T2DM. The additive effect of silymarin in metformin therapy can mitigate fatty liver development in the pre-diabetic state and before the onset of diabetes.

• Klíčová slova
• combination therapy, liver steatosis, metformin, pre-diabetes, silymarin,
• Publikační typ
• časopisecké články MeSH

Hypolipidemic and cardioprotective effects of statins can be associated with the development of myopathies and new-onset type 2 diabetes. These adverse effects may be related to increased oxidative stress. The plant extract silymarin (SM) is known for its antioxidant and anti-inflammatory actions. We tested the hypothesis that the combination of atorvastatin (ATV) with SM could improve therapy efficacy and eliminate some negative effects of statin on hypertriglyceridemia-induced metabolic disorders. Hereditary hypertriglyceridemic rats were fed a standard diet for four weeks without supplementation; supplemented with ATV (5 mg/kg b. wt./day) or a combination of ATV with 1 % micronized SM (ATV+SM). ATV treatment elevated plasma levels of HDL-cholesterol (p<0.01), glucose and insulin and decreased triglycerides (p<0.001). The combination of ATV+SM led to a significant reduction in insulin, an improvement of glucose tolerance, and the hypolipidemic effect was enhanced compared to ATV alone. Furthermore, ATV supplementation increased skeletal muscle triglycerides but its combination with SM decreased triglycerides accumulation in the muscle (p<0.05) and the liver (p<0.01). In the liver, ATV+SM treatment increased the activities of antioxidant enzymes, glutathione and reduced lipid peroxidation (p<0.001). The combined administration of ATV with SM potentiated the hypolipidemic effect, reduced ectopic lipid accumulation, improved glucose metabolism, and increased antioxidant and anti-inflammatory actions. Our results show that SM increased the effectiveness of statin therapy in a hypertriglyceridemic rat model of metabolic syndrome.

• MeSH
• anticholesteremika škodlivé účinky   MeSH
• antioxidancia farmakologie   MeSH
• atorvastatin škodlivé účinky   MeSH
• diabetes mellitus 2. typu chemicky indukované   farmakoterapie   patologie   MeSH
• hypercholesterolemie krev   MeSH
• hyperlipidemie farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• krysa rodu Rattus MeSH
• metabolický syndrom farmakoterapie   genetika   patologie   MeSH
• modely nemocí na zvířatech MeSH
• oxidační stres účinky léků   MeSH
• silymarin farmakologie   MeSH
• triglyceridy krev   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anticholesteremika MeSH
• antioxidancia MeSH
• atorvastatin MeSH
• silymarin MeSH
• triglyceridy MeSH

Veterinarians can recommend milk thistle for the treatment of equine liver disease and laminitis. Milk thistle seed cakes were fed in the range of normal feed doses in this study. The milk thistle seed cakes were fed (twice a day) to the experimental group of the horses (n = 5) and biochemical blood markers (TP, Albumin, ALT (alanine transaminase), AST (aspartate transaminase), ALP (alkaline phosphatase), GGT (gamma-glutamyltransferase), Bilirubin, Cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), TAG (triacylglycerol), BHB (beta-hydroxybutyric acid), NEFA (non-esterified fatty acids), creatine kinase, creatinine, Urea, GSH-Px (glutathione peroxidase), TAS (total antioxidant status), lactate, glucose, cortisol, Ca, Pi) were monitored. The control group of horses (n = 5), bred and trained in the same conditions, was used for comparison. The control group received the entire feed dose as accepted by the horses in the experimental group before the beginning of the experiment. The aim was to find out whether the preparation of milk thistle seed cakes could have positive effects on the health of the horses. All ten horses received one feeding form before the beginning of the experimental monitoring. All horses were exposed to heavy physical exercise (regular combined driving training) after 56 days of milk thistle seed cakes feeding (up to 400 g/day). Three blood samples were taken (before physical exercise; about 15 min and 60 min after physical exercise). Significant differences (p < 0.05) were detected in the values of AST, NEFA, cortisol and Pi in the experimental group. The exercise effect was detected in the values of albumin, lactate, cortisol, NEFA, and calcium. Our results suggest that the feeding of milk thistle seed cakes could have a positive effect on the health of the horses.

• Klíčová slova
• biochemical parameters, horse nutrition, physical exercise, phytogenics, silymarin,
• Publikační typ
• časopisecké články MeSH