Histological and immunohistochemical study of the possible protective effect of folic acid on the methotrexate- induced cardiac muscle toxicity in male albino rats

Abstract

Introduction: Methotrexate is widely used as a chemotherapeutic agent in cancers, ectopic pregnancies and rheumatic arthritis. Folic acid is found in dark green leafy vegetables. Methotrexate is folic acid antagonist that prevents its conversion to tetrahydro folic acid. Aim: This research aimed to study the protective effect of folic acid on the histological changes produced by methotrexate in cardiac muscles. Materials and Methods: Thirty adult male albino rats were divided into three equal groups. Group I (control group) 10 rats injected intraperitoneally with saline. Group II rats were intraperitoneally injected with methotrexate at a dose of 5mg/kg/day for one month. Group III: were intraperitoneally injected with methotrexate at a dose of (5mg/kg/day) with concomitant oral folic acid at a dose of (0.1mg/kg/day) for one month. After 24 hrs of the last dose, the animals were dissected. Hearts were processed for haematoxyline and eosine stain, immunohistochemical stains and electron microscopic examination. Results: Both degenerative and apoptotic changes were observed in the cardiac muscles in the methotrexte-treated group, these changes were attenuated by administration of folic acid. Conclusion: Folic acid is beneficial to the cardiac muscles during methotrexate treatment and should be used concomitant with methotrexate treatment.

Evaluation of the Anticancer Effect of Saussurea costus Root Extract Against Induced Hepatic and Renal Cancer in White Mice: A Histopathological Study

“…In the current study, liver and kidney sections of mice in Group 5/ cancer treated with chemotherapy (2.5mg/Kg Ebetrex) revealed diverse severe histopathological sections at different treatment periods, which became more severe at 5th week, indicating the advanced stages of cancer. These results agree with previously reported studies (Hersh et al, 1966;Tobias and Auerbach, 1973;Doha et al, 2018). These studies approved the hepatotoxicity, kidney damage, and administration disorders of Ebetrex as anticancer.…”

Vitamin D: An effective therapy against methotrexateinduced cardiotoxicity

“…In the present study, 20 mg/kg MTX caused significant histopathological damage to cardiac structure in MTX group, which corroborates earlier research results in rodents [1,8]. The electron microscopic findings of the current study including vacuoles, myofibrillar and mitochondrial damage in cardiomyocytes, supported cardiotoxicity on an ultrastructural level, which was similar to earlier research [12,13]. The MTX causes generation of ROS and this leads to mitochondrial injury, resulting in lower mitochondrial adenosine triphosphate, mitochondrial matrix swelling, and cytochrome c release [14].…”

“…In the current study, MTX-treated rats showed substantially increased expression of caspase-3 in cardiac tissue. These results were supported by several studies where MTX injection was linked to increased apoptosis [1,13,14]. The most likely trigger of apoptosis is excessive ROS generation after MTX exposure that results in mitochondrial outer membrane disruption and cytochrome c release, which in turn activates caspase-3 [14].…”

“…Throughout the experiment, researchers followed the rules established by the Principles for Laboratory Animal Care [13]. Ethical approval for this study was obtained from the Animal Research Ethics Committee of Kahramanmaras Sutcu Imam University, (approval no.…”

Toxicological Studies on The Effect of Methotrexate on Prenatal Rat Foetuses

“…Congestion, cardiomyocyte degeneration, necrotic areas, infiltration of inflammatory leucocytes, and a lack of regular arrangement were observed. Similar results of (Abdel-Daim et al, 2017, Mohamed et al, 2018and Mahmoud et al, 2021 who reported toxicity symptoms, like massive myocardial fiber degeneration, blood vessel congestion, leukocytic infiltration, necrosis and apoptosis, dark eosinophilic cardiac muscle cells with small pyknotic nuclei as well as interstitial oedema in cardiac muscle fibers. In addition, the use of MTX caused histopathological cardiac tissue damage (Tousson et al, 2016).…”