Toxicol Appl Pharmacol. 2007 Jun 21; : 17658574 PubMed

Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration.

MitoSciences, Inc., 1850 Millrace Drive, Eugene, OR 97403, USA
Sashi Nadanaciva , James A Dykens , Autumn Bernal , Roderick A Capaldi , Yvonne Will

Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II+III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II+III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others.

and useful for me. Thank you.

I see that atorvastatin is missing in this study. Given the huge push right now in doctor's offices, I'd like to know it relative status.

I appreciate your posts with studies like this!

the web site of the company for whom the authors work is quite interesting:
http://www.mitosciences.com/parkinsons.html

Seems to be at odds with the study in this thread:

http://neurotalk.psychcentral.com/sh...ighlight=zocor

In the study first mentioned, only one specific statin, simvastatin, reduced the risk of PD by 50%, and they suggested it may be because it enters the brain easily. Other statins like Lipitor did not do the trick.

I've been taking zocor (simvastatin) for a few years.

"The researchers speculate that the selective benefit observed with simvastatin might be due to the combination of high potency and the ability to enter the brain."

simvastatin has been found to be the most lipophilic of the statins, and thus crosses the blood brain barrier easiest, and pravastatin the least (pravastatin is hydrophilic). atorvastatin (lipitor) is thought to be intermediate in ability to cross the BBB, but all the lipophiic statins (fat soluble ones) are found in the cerebral spinal fluid, and thus theorized to cross the BBB.
there is no question that statins are great anti-inflammatory agents and increase perfusion everywhere--the other "pleiotropic" effects are of concern to me. statins interfere with the mevalonate pathway, many steps removed from its effect upon cholesterol.

http://www.cholesterol-and-health.co...olesterol.html

I found it looking around the net today.