Rosuvastatin

Statins are pharmacological inhibitors of the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), an enzyme responsible for the synthesis of cholesterol. Some recent experimental studies have shown that besides their effects on the primary and secondary prevention of cardiovascular disease, statins may also have beneficial anti-inflammatory effects through diverse mechanisms. On the other hand, the induction and activity of regulatory T cells (Treg) are key processes in the prevention of pathology during chronic inflammatory and autoimmune diseases. Hence, strategies oriented towards the therapeutic expansion of Tregs are gaining special attention among biomedical researchers. The potential effects of statins on the biology of Treg are of particular importance because of their eventual application as in vivo inducers of Treg in the treatment of multiple conditions. In this paper we review the experimental evidence pointing out to a potential effect of statins on the role of regulatory T cells in different conditions, and discuss its potential clinical significances.

Concerns have been raised because of observations of proteinuria associated with rosuvastatin treatment. In this open-label study, a potential dose-dependent effect was investigated of rosuvastatin on urinary protein excretion and renal function parameters in 90 hyperlipidemic patients randomly assigned to rosuvastatin 10 mg/day (n = 45) or 20 mg/day (n = 45). Urinary samples were collected from patients and 40 age- and gender-matched controls to determine electrolyte, uric acid, creatinine, and protein (total, albumin, IgG, and α1-microglobulin) levels at baseline and after 12 weeks. A dose-dependent increase in the excretion of α1-microglobulin (17.6% in rosuvastatin 10 vs 34.9% in rosuvastatin, 20 mg/day; P = .03 for the comparison between groups) was observed. A trend toward an increase in the estimated glomerular filtration rate was noted in only patients receiving 20 mg/day of rosuvastatin. These findings indicate that rosuvastatin treatment increases the urinary excretion of ...

AIM Besides a cholesterol-lowering effect, rosuvastatin (RUV) possesses antioxidant and anti-inflammatory properties. The present study investigates the possible protective effects of RUV in diabetes-induced reproductive damage in rats. MAIN METHODS Diabetes was induced in male Wistar rats by injecting a single dose of streptozotocin (65mg/kg, i.p.). RUV in low and high doses (5 and 10mg/kg, p.o.) were administrated to diabetic rats for 8weeks. Reproductive damage was evaluated by estimation of testes and epididymis relative weights and caudal sperm count and motility in the control, untreated and RUV-treated diabetic rats. In addition, testicular malondialdehyde, reduced glutathione and nitric oxide levels, as well as, superoxide dismutase and myeloperoxidase activities were estimated. Finally, expressions of inflammatory [inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB)] and apoptotic (caspase-3) markers besides histological examination of testicular tissues were performed. KEY FINDINGS Results showed that RUV improved sperm count and motility with decrease in testicular nitric oxide and malondialdehyde levels, as well as, myeloperoxidase activity and increase in reduced glutathione level and superoxide dismutase activity in diabetic rats. Further, RUV reduced testicular inflammation and cell death by decreasing the expressions of iNOS, NF-κB and caspase-3. SIGNIFICANCE Treatment with RUV protects against diabetes-induced testicular damage, in a dose dependent manner, through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.

We compared the effects of lipid lowering with rosuvastatin (RSV) monotherapy versus intensified treatment by combining RSV with ezetimibe (EZT) on kidney function in patients undergoing vascular surgery. Patients were randomly assigned to either 10 mg/d RSV (n = 136) or RSV 10 mg/d plus EZT 10 mg/d (RSV/EZT, n = 126). At 12 months, a similar decrease in estimated glomerular filtration rate (eGFR) was noted. Patients who achieved a low-density lipoprotein cholesterol (LDL-C) of <100 mg/dL had less eGFR decrease than those patients having an LDL-C limit of more than 100 mg/dL. There were no significant changes in the urinary total protein to creatinine ratio in either group. Significant microalbuminuria was evident in both the groups. Patients undergoing vascular surgery show deterioration in their renal function during the first year, despite statin therapy. Intensified lipid-lowering therapy by adding EZT does not appear to have any renoprotective effect.

Objective: To report a case describing resolution of persistently elevated aminotransferases in a patient with severe, resistant nonalcoholic fatty liver disease (NAFLD) using combination therapy. Case Summary: A 47-year-old obese male patient presented with a history of elevated aminotransferases and numerous statin intolerances. In addition to worsening control of diabetes and dyslipidemia, severe NAFLD was confirmed. Rosuvastatin was started, which induced short-term elevations in aminotransferases resulting in patient discontinuation. Biochemical markers of NAFLD worsened over time. Therefore, both rosuvastatin 20 mg daily and pioglitazone 15 mg daily were started simultaneously to potentially blunt the early increase in transaminases seen with rosuvastatin. At 2 weeks, the patient’s alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had decreased 57% and 56% from baseline, respectively. By 9 months, the patient’s ALT and AST serum concentrations had normalized....

Background Rosuvastatin is a 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme inhibitor that is in wide use with few reported ocular adverse events. Objectives To report a case of bilateral neurotrophic keratopathy associated with rosuvastatin therapy that dramatically improved following drug discontinuation. Case presentation A 65-year-old female presented with painless diminution of vision in both eyes of gradual onset and progressive course for 1 month. She had recently started rosuvastatin therapy for hyperlipidemia. Examination revealed bilateral stage 2 neurotrophic keratopathy with impaired corneal sensation which was previously resistant to conservative ulcer treatment. Following discontinuation of rosuvastatin therapy, there was dramatic bilateral improvement in corneal sensation, size of the corneal ulcers, and visual acuity. Conclusion Rosuvastatin may result in reversible trigeminal nerve impairment and neurotrophic keratopathy.

Background
Rosuvastatin is a 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme inhibitor that is in wide use with few reported ocular adverse events.
Objectives
To report a case of bilateral neurotrophic keratopathy associated with rosuvastatin therapy that dramatically improved following drug discontinuation.
Case presentation
A 65-year-old female presented with painless diminution of vision in both eyes of gradual onset and progressive course for 1 month. She had recently started rosuvastatin therapy for hyperlipidemia. Examination revealed bilateral stage 2 neurotrophic keratopathy with impaired corneal sensation which was previously resistant to conservative ulcer treatment. Following discontinuation of rosuvastatin therapy, there was dramatic bilateral improvement in corneal sensation, size of the corneal ulcers, and visual acuity.
Conclusion
Rosuvastatin may result in reversible trigeminal nerve impairment and neurotrophic keratopathy.

Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA)
reductase inhibitors exert neuroprotective functions in animal
models of neurodegenerative disorders. In view of these
promising observations, we were interested in whether
HMG-CoA reductase inhibition would affect epileptiform
activity in the brain. To elucidate this issue, atorvastatin,
simvastatin and rosuvastatin were administered orally at a
dose of 20 mg/kg each for 3 days and their anti-epileptic
activities were tested and compared in rats. Epileptiform
activity in the brain was induced by an intracortical
penicillin G injection. Among HMG-CoA reductase inhibitors,
simvastatin-treatment was less effective in terms of
spike frequency as compared with atorvastatin- and rosuvastatin-
treated animals. Atorvastatin treatment reduced
spike frequencies and amplitudes significantly throughout
the experiment. However, the most pronounced anti-epileptic
effect was observed in rosuvastatin-treated animals, which
was associated with improved blood–brain barrier (BBB)
integrity, increased expression of endothelial nitric oxide
synthase (eNOS) mRNA and decreased expressions of
pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition
of eNOS activity with L-NG-Nitroarginine Methyl Ester
(L-NAME) reversed the anti-epileptic effect of rosuvastatin
significantly. However, L-NAME did not alter the effect of
rosuvastatin on the levels of p53, Bax and caspase-3 mRNA
expression. Here, we provide evidence that among
HMG-CoA reductase inhibitors, rosuvastatin was the most
effective statin on the reduction of epileptiform activity,
which was associated with improved BBB permeability,
increased expression of eNOS and decreased expressions
of pro-apoptotic p53, Bax and caspase-3. Our observation
also revealed that the anti-epileptic effect of rosuvastatin
was dependent on the increased expression level of eNOS.
The robust anti-epileptic effect encourages proof-of-concept
studies with rosuvastatin in human epilepsy patients with
hypercholesterolemia.