Amethopterin is used as a chemotherapeutic agent, and its antioxidant activity is used to treat many cancer types. This study aimed to study the ameliorating effect of L-carnitine against amethopterin-induced cardiac injury and oxidative stress in male rats. Sixty male albino rats were equally divided into six groups; the first and second groups were the control and L-carnitine groups, respectively, while the third group was treated with amethopterin rat group; the fourth and fifth groups were co-treated and post-treated with amethopterin rat with L-carnitine, respectively, and the sixth group was self-treated with amethopterin rat group. Cholesterol, triglycerides, low-density lipoprotein (LDL), glutathione, and total protein levels in amethopterin group showed a significant decrease when compared with control group, while high-density lipoprotein (HDL), glutamic oxaloacetic transaminase (GOT), malondialdehyde (MDA), catalase, and nitric oxide (NO) levels in amethopterin group showed a significant increase when compared with control group. Cholesterol, triglycerides, LDL, GOT, MDA, and catalase levels in the self-treated group showed a significant increase when compared with amethopterin group, while glutathione, total protein, and NO levels in the self-treated group showed significant decrease when compared with amethopterin group. Many of abnormalities as moderate hydrophobic changes of myofibrillar structure with striations, myocardial atrophy, cytoplasmic vacuoles, edema, and leukocyte infiltration were detected in cardiac tissues in amethopterin rat group. A significant increase of the apoptotic protein p53 and CD68 immunoreactivity, despite a significant decrease in the antiapoptotic Bcl–2 proteins after amethopterin injection when compared with control group, was observed. Treatment (co and post) with L-carnitine improved the biochemical, histopathological, and immunohistochemical alterations in the heart treated with amethopterin.
