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Background & Objective: Tetra Carbon Cholride has been known as reference hepatotoxin because it can cause necrosis, fatty change, cirrhosis and cancer liver. Silymarin has hepatoprotective and anti hepatoxin effect. This study was done to determine the protective effect of Silymarin in acute hepatotoxicity of CCl4 in rats.

Materials & Methods: In this experimental study, we chose 25ml/kg dose of CCl4 (in mineral oil solvent) as an optimum dose. The hepatotoxic effects of intraperiotoneal injection of CCl4 for obtaining parameters of toxicity and therapeutic effects have been examined. According to enzymatic results (increase in ALT and AST) and histopathologic changes (grading the changes in liver including cytoplasmic granularity, cloudy swelling, necrosis and fatty change), the interval between prescribing silymarin and sampling  was determined. Silymarin as a suspension in propylene glycol CMC 2% (3/2 ratio) has been prescribed in 50, 200 and 800mg/kg doses and serum and liver samples were obtained. Negative control group received silymarin vehicle in CCl4 solvent, drug control received 800 mg/kg of silymarin in CCl4 solvent and positive control received silymarin vehicle after injecting CCl4.

Results: The results showed that prescribing 50mg/kg silymarin one hour after injecting CCl4, in addition to inhibiting transaminase activity, prevents progress of liver injury up to 50% of positive control group. Cellular repair and regeneration are also enhanced, So the grade 3necrosis in positive control group is decreased to grade 0.5 in silymarin gourp in 48 hours prescribing silymarin (50mg/kg).

Conclusion: This study showed that up to six hours after injecting CCl4 significantly prevents hepatotoxicity, and cause acceleration in repair of liver injuries.

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Background and Objective: Chronic diabetes mellitus is accompanied with enhanced oxidative stress and reduce the activity of antioxidant defense system. Due to significant role of enhanced oxidative stress in development of renal damage in diabetices, this study was conducted to evaluate the effect of chronic administration of Silymarin on oxidative stress markers in renal tissue of diabetic rats. Materials and Methods: In this experimental study, 40 male Wistar rats were divided into 5 groups: control, silymarin-treated control (100 mg/kg bw), diabetic, and silymarin -treated diabetic groups (50 and 100 mg/kg bw). Silymarin was administered (daily and intraperitonealy) ten days after Streptozotocin injection for 4 weeks. Tissue level of malondialdehyde and nitrite and nitrate and activity of superoxide dismutase in kidney tissue were measured. Data were analyzed using ANOVA and Tukey tests. Results: A significant increase in tissue level of malondialdehyde, nitrite and nitrate in diabetic rats were observed (P<0.05). Silymarin treatment (100 mg/kg/bw) significantly reduced the tissue level of Malondialdehyde, nitrate and nitrate (P<0.05). Non-significant recduction of activity of superoxide dismutase was oberved in diabetic rats and Silymarin treatment (50 and 100 mg/kg bw) did not significantly altered enzyme activity. Conclusion: Four weeks treatment of Silymarin (100 mg/kg bw) reduce oxidative stress indexes in renal tissue of diabetic rats.

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Background and Objective: Diabetes mellitus cause learning, memory and cognitive skills disorders in the long term. This study was conducted to determine the protective effect of silymarin on the learning and memory deficiency in streptozotocin-diabetic rats. Materials and Methods: This experimental study was conducted on 40 male Wistar rats weighing 240-300 grams. The rats were randomly allocated into 5 groups: control, silymarin -treated control (100 mg/kg), diabetic, and two silymarin -treated diabetic groups (50 and 100 mg/kg). Silymarin was daily administered (i.p. and daily) ten days after streptozotocin injection for 4 weeks. Finally, initial (acquisition index) and step-through latencies (retention and recall index) were measured using passive avoidance test and alternation behavior percentage as an index of spatial memory was determined using Y maze. The level of malondialdehyde in the homogenate hippocampal tissue of the animals brains was measured. Data were analyzed using Sigma Stat-3.5, one-way and two-way ANOVA, Tukey, and Kruskall-Wallis tests. Results: A significant reduction of STL was observed in diabetic (P<0.01) and silymarin-treated (50mg/kg) diabetic (P<0.05) groups and this parameter was significantly higher in diabetic group receiving a high dose of silymarin compared to diabetic group (P<0.05). Meanwhile, alternation percentage in diabetic animals was significantly lower than control group (P<0.05) and this index did not show a significant difference in silymarin-treated diabetic groups in comparison with diabetic group. In diabetic rats, there was a significant increase in the tissue level of malondialdehyde (P<0.05) and silymarin treatment with dosage of (100 mg/kg) significantly reduced the level of MDA (P<0.05). Conclusion: This study showed that although long-term administration of silymarin at a high dose (100 mg/kg) affects the ability to store data in memory and to recall it in diabetic animals in passive avoidance test, it does not improve short-term spatial memory in diabetic animals. The beneficial effects of silymarin may be via attenuation of lipid peroxidation in hippocampus tissue.

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Background and Objective: Leptin is associated with metabolic disorders and promotes the development of liver steatosis to steatohepatitis. It selectively increases the secretion of Tumor-necrosis factor-α (TNF-a) in response to saturated fatty acid. The general purpose of this research was to determine the effects of eight weeks of continuous training and silymarin supplementation on the serum levels of TNF-α and leptin in Wistar rats with fatty liver disease.
Methods: In this experimental study, 40 male Wistar rats aged three weeks and weighting 159±3 grams were randomly divided into five groups: normal diet/saline, high-fat diet/saline (control), high-fat diet/supplemented, high-fat diet/exercise/saline, and high-fat diet/exercise/supplement. The rats were fed 10 grams per 100 grams of body weight (standard diet 13% fat and high-fat diet 41% fat) for eight weeks, and silymarin (140 mg per kilogram body weight) were given by gavage for 2 weeks. The continuous aerobic exercise protocol consisted 30 minutes of treadmill running at 70-75% of VO₂max for eight weeks, five days a week. After sacrificing the animals, samples were taken and sent to the laboratory for histological analysis. The expression of leptin and TNF-α in the liver was measured using commercial ELISA kits.
Results: The findings showed a greater decrease in hepatic leptin concentration in the high-fat diet + continuous exercise + supplement group (P<0.05) compared to the high-fat diet + continuous exercise + saline group (P<0.05). Tukey's post hoc test showed a greater decrease in the concentration of hepatic TNF-α in the high-fat diet + saline group (compared to the high-fat diet + supplement group) (P<0.05), and the high-fat + exercise + saline group (P<0.05). The weight of the rats in the normal diet + saline group differed significantly from other groups (P<0.05).
Conclusion: The results indicated that the combination of continuous training with silymarin supplementation can help reduce leptin and TNF-α in rats with a high-fat diet, an effect not observed by silymarin supplementation alone. Therefore, the combination of continuous aerobic exercises and silymarin supplementation can further oxidize fat and reduce inflammation in the body.