RESUMO
Methotrexate (MTX) is an antimetabolite used to treat inflammatory diseases, autoimmune disorders and some malignancies. However, it has some life-threatening side effects such as nephrotoxicity which limit its clinical applications. That motivated the attention to seek for a defensive material to improve the outcomes of methotrexate while minimizing both renal and non-renal toxicity. Both honey (H) and olive oil (OO) are bioactive substances widely used as nutraceuticals that exhibited a potent therapeutic and antioxidant properties. This study aimed to assess the possible protective effect of H and OO intake either singly or together against the biochemical and structural Methotrexate-induced nephrotoxicity in rats. The study was conducted on 56 adult albino rats, they were divided into seven groups (n = 8): group 1 received only distelled water (negative control), group 2 received H (1.2 g/kg/day), group 3 received OO (1.25 ml/kg/day), group 4 received a single intraperitoneal injection of MTX (20 mg/kg), group 5 received MTX and H, group 6 received MTX and OO, group 7 received MTX, H and OO together. At the end of the experiment (2 weeks), all rats were sacrificed, and blood samples were assessed for kidney function tests. Kidney tissues were evaluated for several antioxidant parameters including Malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. Tissues were also processed for histological and immunohistochemical assessments. Results revealed that both H and OO improved the kidney function markers, histopathological and immunohistological changes due to Methotrexate-induced renal damage. Additionally, both substances also redeemed the oxidative damage of the kidney by decreasing MDA and increasing anti-oxidant enzymatic activities. Such effects were more apparent when the two substances were given together. Ultimately, our results proof that H and OO amiolerate the Methotrexate-induced nephrotoxicity in rats, thus they can be used as an adjuvant supplements for patients requiring methotrexate therapy.
RESUMO
Adriamycin (ADR) efficacy in cancer chemotherapy is well-established. However, ADR-induced cardiotoxicity remains a significant challenge. Aged garlic extract (AGE) is a natural polyphenol with high antioxidant potential. This study was planned to determine the cytoprotective and antioxidant actions of AGE against the cardiotoxic effect of ADR in rats. Six equal groups, control, ADR-treated (single dose of 10 mg/kg on day 8); AGE-treated (one dose of 250 mg/kg for 14 days); AGE plus ADR-treated (one dose of 250 mg/kg AGE for one week plus ADR injection of 10 mg/kg on day 8); ADR plus AGE-treated (single ADR injection of 10 mg/kg on day 8 plus AGE of 250 mg/kg once from 8th to 14th day); combined AGE plus ADR plus AGE-treated (one dose of 250 mg/kg AGE for 14 days plus single ADR injection of 10 mg/kg on day 8). Sera and cardiac samples were collected on day 15 and prepared for histological, ultrastructural and biochemical study. Disorganization, focal degeneration and necrosis with apoptotic changes of the cardiac myofibrils were observed in ADR-treated rats. Also, reduction in level of total creatine kinase, lactic dehydrogenase, alkaline phosphatase enzymes, glutathione, glutathione- peroxidase, superoxide dismutase, and catalase activities and elevation in malondialdehyde concentration were detected in ADR-treated rats. However, combination of AGE attenuated most of the histopathological, ultrastructural, and biochemical changes induced by ADR. Combination of AGE attenuated the cardiotoxic effects-induced by ADR through its antioxidant and cytoprotective potentials. Therefore, AGE can use as adjunct during administration of ADR in cancer therapy.
