Effects of Catha edulis Extract on Atorvastatin-Induced Myotoxicity in Rats: Biochemical and Histopathological Evidence

Abstract

Background: Rhabdomyolysis is a complex disorder caused by muscle cell injury and the subsequent release of intracellular components into circulation. Statins are widely used and generally well tolerated; however, some patients report muscle weakness, particularly in the lower extremities. Concomitant use of statins with herbal products such as khat (Catha edulis) may increase the risk of adverse events. Aim: This study evaluated the effects of khat extract on atorvastatin-induced rhabdomyolysis in rats. Methods: Methanolic extraction of khat leaves was performed, and phytochemical analysis confirmed alkaloids, tannins, flavonoids, and other bioactive compounds. Twenty-four healthy rats were randomly divided into four groups: control, khat extract (500 mg/kg), atorvastatin (40 mg/kg), and khat extract plus atorvastatin. Treatments were administered orally for 28 days. Blood samples were analyzed for myoglobin, creatine kinase, lactate dehydrogenase, alkaline phosphatase, fast skeletal troponin, creatinine, albumin, and total protein. Skeletal muscle and kidney tissues were examined histopathologically. Results: The khat-atorvastatin group showed significant weight reduction and marked elevations in biochemical markers. Histopathology confirmed severe muscle necrosis and kidney tubular injury in the combined-treatment group, while mild myopathy was evident in the khat-only and atorvastatin-only groups. Conclusion: Khat extract contributes to biochemical and histopathological changes indicative of muscle injury. Combined use with atorvastatin exacerbates these effects and may increase the risk of rhabdomyolysis and renal complications.