Immunosuppressive drugs used in the transplantation period are generally defined as induction and maintenance therapy. The use of immunosuppressants, which are particularly useful and have fewer side effects, decreased both mortality and morbidity. Many drugs such as steroids, calcineurin inhibitors (cyclosporine-A, tacrolimus), antimetabolites (mycophenolate mofetil, azathioprine), and mTOR inhibitors (sirolimus, everolimus) are used as immunosuppressive agents. Although immunosuppressant drugs cause many side effects such as hypertension, infection, and hyperlipidemia, they are the agents that should be used to prevent organ rejection. This shows the importance of individualized drug use. The optimal immunosuppressive therapy post-transplant is not established. Therefore, discovering less toxic but more potent new agents is of great importance, and new experimental and clinical studies are needed in this regard. Our review discussed the mechanism of immunosuppressants, new agents' discovery, and current therapeutic protocols in the transplantation.
In this study, the authors aimed to investigate the role of oxidative stress on the hepatic damage caused by methotrexate (MTX) and the possible protective effects of β-carotene against this damage. The rats were divided into four groups as control, MTX (20 mg/kg ip), β-carotene (10 mg/kg/day ip) + MTX, and β-carotene. Histopathologic alterations were evaluated for defining the liver damage. The tissue, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GP-x) contents and serum aspartate aminotransferase (AST) and alanine aminotranferase (ALT) activities were also examined. Histopathologic damage for each group score findings have been determined as control: 0.66 ± 0.33; MTX: 7.0 ± 0.68; β-carotene + MTX: 3.3 ± 0.42; and β-carotene: 0.5 ± 0.3. In the MTX-treated group, MDA, AST, and ALT values were increased, while SOD and GP-x values were decreased compared with the control group. In the β-carotene + MTX-treated group, AST and ALT values significantly decreased, while all other parameters were similar to the control group. This study shows that β-carotene has a protective effect on MTX-induced oxidative hepatic damage. Consequently, it seems that an antioxidant agents like β-carotene may be useful in decreasing the side effects of chemotherapy.