No abstract

No abstract

Methotrexate (MTX) is an antineoplastic and anti-inflammatory agent which is used in severe diseases. Its use should be limited due to side effects such as nephrotoxicity, myelotoxicity and hepatotoxicity. Nebivolol (NBV), which is a beta blocker and used in the treatment of hypertension, also contributes to vasodilation in tissues by activating endothelial nitric oxide synthase (eNOS) enzyme. The purpose of this study is to research the effect of NBV on MTX-induced nephrotoxicity through the AKT1/Hif-1⍺/eNOS signaling pathway. The rats were randomly divided into three groups of eight each. Groups were control, MTX and MTX+NBV. A single dose of 20 mg/kg MTX was given intraperitoneally to the rats on the first day of the study and 10 mg/kg NBV was given orally to the treatment group for seven days. At the end of the study, rats' blood and kidney tissues were taken for histopathological, immunohistochemical and biochemical examinations. MTX administration was significantly decreased the expression levels of AKT1, eNOS and Hif1α compared to control group (p<0.001 for all), and NBV treatment increased these values compared to MTX group (p<0.001 for all). In conclusion, NBV treatment ameliorated the MTX induced nephrotoxicity via AKT1/Hif-1⍺/eNOS signaling pathway.

Methotrexate (MTX) is an antineoplastic and anti-inflammatory agent which is used in serious diseases. Its use should be limited due to side effects such as nephrotoxicity, myelotoxicity and hepatotoxicity, especially during high doses in cancer treatment. Hypertension may accompany patients due to nephrotoxicity, which is shown as one of the most important side effects. Nebivolol (NBV), which is a beta blocker and used in the treatment of hypertension, also contributes to vasodilation in tissues by activating endothelial nitric oxide synthase (eNOS) enzyme. The purpose of this study is to research the effect of NBV on MTX-induced nephrotoxicity through the AKT1/Hif-1⍺/eNOS signaling pathway. The rats were randomly divided into three groups of eight each. Groups were control, MTX and MTX + NBV. A single dose of 20 mg/kg MTX was given intraperitoneally to the rats on the first day of the study and 10 mg/kg NBV was given orally to the treatment group for seven days. At the end of the study, rats' blood and kidney tissues were taken for histopathological, immunohistochemical and biochemical examinations. Total antioxidant status levels were increased and total oxidant status levels were decreased significantly in MTX + NBV group compared with MTX group. Although creatinine levels increased in the MTX group compared to the control, while decreased in the MTX + NBV group. MTX administration was significantly decreased the expression levels of AKT1, eNOS and Hif1α compared to control group and NBV treatment increased these values compared to MTX group. In conclusion, NBV treatment ameliorated the MTX induced nephrotoxicity via AKT1/Hif-1⍺/eNOS signaling pathway.

Background Systemic inflammation is a fatal condition that affects many tissues or organs. This pathological inflammation process, which can cause acute and chronic kidney damage, plays an important role in the structural and functional damage in various kidney diseases. Selenium (Se) is an antioxidant and anti-inflammatory trace element. In this study, we aimed to examine the effects of Se, which has antioxidant and anti-inflammatory properties, on lipopolysaccharide (LPS)-induced kidney damage to maintain Aquaporin-1 (AQP-1) levels. Methods and Results Four experimental rat groups (n = 8) consisting of the control (1 mL saline), LPS alone (0.1 mg/kg), LPS + Se (0.1 mg/kg + 4 mg/kg) and Se alone (4 mg/kg) were so applied for 7 consecutive days. Upon sacrifice, histopathological results, diagnostic markers of kidney functions, oxidative stress, and inflammation were analyzed. Our results showed that LPS induced mononuclear cell infiltration, cellular residue and protein deposition in the kidney proximal tubules, and also decreased total antioxidant status levels, which is a marker of antioxidant capacity, and increased total antioxidant status and oxidative stress index values, which are indicators of oxidative stress. LPS increased the level of creatinine, which is an indicator of kidney damage, increased the level of Nuclear Factor kappa B, which has an important role in the inflammation process, and decreased the levels of AQP-1 due to the damage it caused. Se has shown its effect by reversing all these situations. Conclusions This data suggests that Se can be used as an additive to mitigate LPS-induced toxicity in the kidney.