Experimental Lovastatin Myopathy

• Published in: Journal of neuropathology and experimental neurology Vol. 52; no. 5; pp. 542 - 549
• Main Authors: WACLAWIK, ANDREW J, LINDAL, SIGURD, ENGEL, ANDREW G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.09.1993; Lippincott Williams & Wilkins
• Subjects: Acid Phosphatase - analysis; Animals; Basement Membrane - drug effects; Basement Membrane - pathology; Basement Membrane - ultrastructure; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Female; Intracellular Membranes - drug effects; Intracellular Membranes - ultrastructure; Lovastatin - toxicity; Medical sciences; Microscopy, Electron; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - ultrastructure; Muscles - drug effects; Muscles - pathology; Muscles - ultrastructure; Muscular Diseases - chemically induced; Muscular Diseases - pathology; Organelles - drug effects; Organelles - ultrastructure; Pharmacology. Drug treatments; Rats; Rats, Inbred Lew; Toxicity: nervous system and muscle; Nervous system diseases; Rat; Enzyme; Toxicity; Rodentia; Enzyme inhibitor; Exploration; Electron microscopy; Pathology; Striated muscle disease; Vertebrata; Mammalia; Animal; Hydroxymethylglutaryl-CoA reductase; Antilipemic agent; Myopathy
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/00005072-199309000-00012

Lovastatin (LS) is a potent HMG-CoA inhibitor used in the treatment of hypercholesterolemia. In humans it can cause a severe, necrotizing myopathy with myoglobinuria and renal failure. To investigate the pathogenesis of LS-induced myopathy we studied the effects of LS on rat skeletal muscle. Lewis rats were gavage-fed 1 mg/g body weight/day of LS. Control rats received carboxymethylcellulosc-based suspension by gavage. Gastrocnemius and soleus, fast and slow twitch muscles respectively, were studied by light and electron microscopy. By day 10 LS-treated rats became severely weak. Gastrocnemius was severely affected with degeneration of membranous organelles and microvacuole formation, but soleus was spared. Eventually, 20–50% of the gastrocnemius but none of the soleus fibers became necrotic. Non-necrotic fibers showed no increases of acid phosphatase, indicating that autophagy was not excited. We conclude that LS causes muscle injury by inducing degeneration of membranous organelles, and fast twitch muscle fibers are selectively vulnerable to LS myopathy.