Elevated Levels of Estrogen Suppress Hepcidin Synthesis and Enhance Serum Iron Availability in Premenopausal Women.

Clinical and experimental observations have long suggested that elevated levels of estrogen associate with increased serum iron availability. Additionally, recent work has shown that estrogen can downregulate hepcidin synthesis in vitro. This study aims at assessing whether the ability of estrogen to downregulate hepcidin synthesis translates into changes in serum iron status. Hepcidin synthesis was evaluated in MCF-7, Hep-G2 and SKOV-3 cells treated with increasing concentrations of estrogen and cultured for up to 24 h post treatment. The correlation between levels of serum estrogen, hepcidin and iron was assessed using serum samples collected from 153 premenopausal women at random and samples collected from 6 women at days 1, 5, 10, 16, 21 and 28 of the monthly cycle. Estrogen-treated MCF-7 cells showed a significant reduction in hepcidin synthesis, especially at 20 nM/24 h E2 treatment. Hepcidin synthesis was also significantly reduced in Hep-G2 and SKOV-3 cells at 20 nM/24 h E2 treatment. In serum samples collected at random, estrogen (P=0.022; R=-0.213) and iron (P=0.028; R=-0.316) correlated negatively with hepcidin and positively with each other (P=0.033; R=0.319). An overall similar pattern was also observed in monthly cycle-timed samples. These findings suggest that elevated levels of estrogen reduce hepcidin synthesis as means of enhancing serum iron content in menstruating women.

Trimetazidine in the prevention of contrast-induced nephropathy in chronic kidney disease.

BACKGROUND: Contrast induced nephropathy (CIN) may be defined as Acute Renal Failure (ARF) that occurs within 24-72h of exposure to intra-venous or intra-arterial iodinated contrast media that cannot be attributed to other causes. CIN occurs in up to 5% of hospitalized patients with normal renal function prior to injection of contrast media. It occurs more frequently in patients with renal impairment particularly if associated with diabetic nephropathy. Among all procedures utilizing contrast agents for either diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary interventions are associated with the highest rates of CIN. Trimetazidine has been described as a cellular anti-ischemic agent. Previous studies demonstrated that Trimetazidine prevents the deleterious effects of ischemia-reperfusion at both the cellular and mitochondrial levels and exerts an anti-oxidant effect. It inhibits excess release of oxygen free radicals, limits cellular acidosis, protects Adenosine Triphosphate (ATP) stores, reduces membrane lipid peroxidation and inhibits neutrophil infiltration. AIM: To evaluate the role of Trimetazidine (TMZ) in prevention of contrast induced nephropathy (CIN) in patients with renal impairment undergoing coronary angiography. METHODS AND RESULTS: This study was conducted on one hundred patients having a basal creatinine clearance below 90ml/min and presenting for coronary angiography procedures. The patients were divided into two equal groups each including fifty patients where both groups received parenteral hydration in the form of isotonic saline at a rate of 1mg/kg body weight per hour starting 12h before angiography and up to 12h thereafter. In Group 1, patients received additional medication in the form of trimetazidine 35mg twice daily for 72h and starting 48h before the procedure which was not received in group 2 (control). There was a significant difference regarding the rate of CIN among TMZ versus control groups (10% vs. 26%). The amount of contrast was significantly higher in the CIN group (165.00±108.41 vs 89.85±38.60, P=0.000). CONCLUSION: Administration of trimetazidine in a dose of 35mg twice daily orally in conjunction with standard early saline hydration is an effective method to prevent or reduce the incidence of contrast-induced renal dysfunction following the administration of contrast media during coronary angiography procedures in patients with mild-moderate basal renal insufficiency.