RESUMO
Objectives: Methotrexate (MTX) is a drug with anti-inflammatory and immunosuppressive effects and is also a folic acid antagonist. Our aim in this study is to determine the molecular mechanisms of cardiotoxicity caused by MTX, a chemotherapeutic drug, and to evaluate the protective effects of vitamin B12 on this toxicity. Materials and Methods: A total of 32 rats were used in our study and 4 groups were formed. Control group, Vit B12 group (3 µg/kg B12 for 15 days, IP), MTX group (20 mg/kg MTX single dose on day 8 of the experiment, IP), MTX +Vit B12 group (3 µg/kg, IP ), Vit B12 throughout the 15 days, and a single dose of 20 mg/kg MTX (IP) on day 8 of the experiment. Immunohistochemically, expressions of hypoxia-inducible factor 1α (HIF1-α), vascular endothelial growth factor receptor-2 (VEGFR-2), erythropoietin (EPO), and interleukin-6 (IL-6) were evaluated in the heart tissue. Total catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the heart tissue. At the same time, ANP and NT-proBNP levels were measured in the blood serum. Results: In the study, the expression of HIF1-α and VEGFR-2 increased significantly in the MTX group, while IL-6 and EPO significantly decreased. At the same time, CAT and SOD levels were significantly decreased and MDA levels increased significantly in the MTX group. While vitamin B12 significantly corrected all these values, it also greatly reduced the increases in ANP and NT-proBNP levels caused by MTX. Conclusion: It is important to use Vit B12 before and after MTX administration to replace the folate that MTX has reduced.
RESUMO
The aim of this work was to study the relative ghrelin and growth hormone secretagogue receptor (GHS-R)1a gene expression in the kidney of long-term diabetic rats. Forty male Wistar albino rats were divided into four groups: C- control group, DI- one month diabetic rats group, DII- two months diabetic rats group, and DIII- three months diabetic rats group. Diabetes was induced by streptozotocin STZ (40mg/kg i.p). The rats were decapitated under ketamine anesthesia and their kidney tissues were removed. Tissue GHS-R mRNA levels, ghrelin expression, and histopathological damage scores were compared. Dilatation in the distal tubules, epithelial desquamation into the lumen of the tubules and transparent tubules showing glycogen vacuolation were observed in all the diabetic groups. Ghrelin immunoreactivity was significantly higher in group DI compared to group C, whereas in groups DII and DIII, ghrelin immunoreactivity was similar with group C. GHSR-1a mRNA level in group DIII was significantly lower than in group C. As a result, ghrelin immunoreactivity increased at the beginning of diabetes; however, with increase in the duration of diabetes ghrelin immunoreactivity approached to the control values. The expression of GHSR-1a mRNA decreased with increase in diabetes duration. It seemed that down-regulation of GHSR-1a contributed to the renal damage induced by long-term diabetes.
