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

Abdulatef Mohammed Mohammed Abbas,1 Safia Abdulatef Abdulruhman Alrezami,1,2 Butheina Abdulwalli Al- Amrani3 1Department of Pharmacy, Faculty of Medicine and Health Science, University of AlMahweet, AlMahweet, Yemen; 2Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, Sana’a University, Sana’a, Yemen; 3Department of Pharmacology, Faculty of Medicine and Health Science, University of Science and Technology (UST), Sana’a, YemenCorrespondence: Abdulatef Mohammed Mohammed Abbas, Email [email protected]: Rhabdomyolysis (RML) 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. The concomitant use of statins with other substances, including herbal products such as khat (Catha edulis), may increase the risk of adverse events. Khat chewing is known to cause multiple health problems and has been associated with musculoskeletal weakness.Aim: This study aimed to evaluate the effects of khat extract on atorvastatin-induced rhabdomyolysis in rats.Methods: Methanolic extraction of khat leaves was performed, and phytochemical analysis confirmed the presence of 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. On day 28, blood samples were collected for biochemical assays of myoglobin, creatine kinase (CK-MM), lactate dehydrogenase (LDH, LDH5), alkaline phosphatase (ALP), troponin fast skeletal (fsTnI), creatinine, albumin, and total protein. Histopathological analysis of skeletal muscle and kidney tissues was also conducted. Data were analyzed using the Kruskal–Wallis, expression by median(IQR), CI(95%) with significance set at p < 0.05.Results: The khat–atorvastatin group showed significant weight reduction and marked increases in biochemical markers compared with controls. The khat-only and atorvastatin-only groups also demonstrated elevated biomarkers but at lower levels. Histopathology confirmed severe muscle necrosis and kidney tubular injury in the khat–atorvastatin 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. When combined with atorvastatin, these effects are exacerbated, leading to pronounced myopathy and kidney damage. These findings suggest that khat use may potentiate statin-induced rhabdomyolysis and increase the risk of musculoskeletal and renal complications.Keywords: rhabdomyolysis, Catha edulis, atorvastatin, biochemical and histopathological analysis