Effects of Rosuvastatin on the expression of the genes involved in cholesterol metabolism in rats: adaptive responses by extrahepatic tissues.

BACKGROUND: Statins mostly target the liver; therefore, increase in the synthesis of cholesterol by extra-hepatic tissues and then transferring this cholesterol to the liver can be regarded as adaptive responses by these tissues. In addition to cholesterol, these adaptive responses can increase isoprenoid units as the byproducts of the cholesterol biosynthesis pathway; isoprenoids play a key role in regulating cell signaling pathways and cancer development. Thus, there is a primary need for in vivo investigation of the effects of statins on the cholesterol metabolism in the extra-hepatic tissues. MATERIALS: Eighteen male Sprague-Dawley rats were randomly divided into control (n = 9) and treatment (n = 9) groups. The treatment group was orally given 10 mg/kg/day of Rosuvastatin for 6 weeks. Then, serum lipid profile, expression levels of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), ABCA1, ABCG1 and ApoA1, and activity of HMGCR were measured in the liver, intestine and adipose tissues. RESULTS: Rosuvastatin significantly reduced total cholesterol and LDL-C. The expression levels of ABCA1, ABCG1, and ApoA1 in the liver and HMGCR in both liver and intestine were significantly increased in the Rosuvastatin treated-group. However, in the intestine, there were no significant differences in the expression levels of ABCA1 and ABCG1 between the study groups. Rosuvastatin had no effect on the adipose tissue. The HMGCR activity was significantly increased in the liver and intestine of the Rosuvastatin-treated group. CONCLUSIONS: In spite of the adipose tissue, the intestine efficiently responses to the reduced levels of cholesterol and increases its cholesterogenesis capacity. However, adipose tissue seems to play a small role in correcting cholesterol deficiency during the course of statin therapy.

Effects of citicoline on level of consciousness, serum level of fetuin-A and matrix Gla-protein (MGP) in trauma patients with diffuse axonal injury (DAI) and GCS≤8.

BACKGROUND: Citicoline, a neuroprotective drug, has been suggested to improve level of consciousness, mitigating secondary to brain damage and ectopic vascular calcification, following post-traumatic neurogenesis and angiogenesis, inducing calcification modulators, like fetuin-A and matrix Gla-protein (MGP). This study aimed to investigate effects of citicoline on levels of consciousness, serum levels of fetuin-A and MGP in patients with severe traumatic brain injury. METHODS: This double blind randomized controlled trial (RCT) was conducted on patients with diagnosis of diffuse axonal injury (DAI) and GCS≤8. The cases were treated with citicoline (500 mg every 6 hours) intravenously for fifteen days. Daily GCS assessment and intermittent blood sampling were done for both cases and controls. RESULTS: Fifty-eight patients were included in the study and during the study period, mean GCS levels improved in both groups; however, the difference was inconsiderable (p>0.05). Serum levels of fetuin-A, a negative phase reactant, increased in the group treated with citicoline (p=0.012), while these changes were insignificant for the controls (p=0.455). Serum levels of MGP, a calcification inhibitor, increased in the cases (p=0.046). The alterations were inconsequential in the control group (p=0.405). CONCLUSION: The findings of this study suggest neutral effects of citicoline on level of consciousness and GCS. Through increasing levels of fetuin-A and MGP, citicoline may have protective effects against inflammatory damage and vascular calcification secondary to head trauma.