Sodium Tungstate Administration Ameliorated Diabetes-Induced Electrical and Contractile Remodeling of Rat Heart without Normalization of Hyperglycemia

Abstract

Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts based on its insulinomimetic activity. In this study, we aimed to investigate the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate. Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for 6 weeks. Blood glucose levels increased, whereas body weight, heart weight and plasma insulin levels decreased significantly in diabetic animals. Interestingly, none of these parameters was changed by tungstate treatment. On the other hand, fractional shortening and accompanying intracellular Ca(2+) [Ca(2+)](i) transients of isolated ventricular myocytes were measured, and sodium tungstate was found to improve the peak shortening and the amplitude of [Ca(2+)](i) transients in diabetic cardiomyocytes. Potassium and L-type Ca(2+) currents were also recorded in isolated ventricular cells. Significant restoration of suppressed I (to) and I (ss) was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in untreated or treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase (XO) and xanthine dehydogenase (XDH) were also determined, and diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate treatment. Conversely, although XO and XDH activities didn't change in untreated diabetic rats, a remarkable but insignificant decrease was detected in treated animals. In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca(2+)](i) and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of hyperglycemia.

Sodium tungstate alleviates biomechanical properties of diabetic rat femur via modulation of oxidative stress

“…Zhen et al (2010) reported that persistent high glucose level is capable of influencing osteoblast differentiation, impairing bone formation and inhibiting bone mineralization possibly via stimulation of oxidative stress production which has been suggested to be an important contributing factor for the incidence of diabetic osteopenia (Bai et al 2004;King and Loeken 2004;Hamada et al 2009;Liang et al 2011). Consistently, many experimental studies, including our previous reports have demonstrated extensive increase in ROS in diabetic animal tissues (Ozdemir et al 2009;Liang et al 2011;Aydemir et al 2012). ROS comprises an array of chemical entities such as oxygen free radicals, hydrogen peroxide, nitric oxide (NO) and peroxynitrite which are produced at low levels even in physiological conditions and scavenged by endogenous antioxidant systems such as GPx, GSH, SOD, and CAT.…”

“…Growing evidence and our previous results suggest that reactive oxygen species (ROS) play an important role in diabetes-induced abnormalities in various tissues and tungstate can reduce the upregulated oxidative stress parameters probably via restoration of antioxidant defense mechanisms (Hamada et al 2007(Hamada et al , 2009Nakhaee et al 2010;Blakytny et al 2011;Aydemir et al 2012). However, despite the above studies reporting the influence of tungstate administration on various tissues, there is no information on the effect of tungstate on bone biomechanical properties in diabetic rats.…”

“…Of these elements, sodium tungstate (Na 2 WO 4 ) which chemically resembles vanadium was shown to have antidiabetic activity in experimental studies based on its suggested insulinomimetic or antioxidant activity (Barbera et al 1994Munoz et al 2001;Aydemir et al 2012). Oral administration of sodium tungstate has been reported to normalize glycemia in many animal models of diabetes (Barbera et al 1994(Barbera et al , 1997Munoz et al 2001).…”

The Effects of Losartan on Lipid Peroxidation and the Antioxidant System in the Bone Tissue of Diabetic Rats

“…(42) yaptıkları çalışmada diyabetik osteopeni insidansı için önemli bir faktör olduğu düşünülen oksidatif stres üretiminin uyarılması yoluyla kalıcı yüksek glikoz seviyesinin, osteoblast farklılaşmasını etkileyebildiğini, kemik oluşumunu bozduğunu ve kemik mineralizasyonunu inhibe edebildiğini bildirmişlerdir. Yapılmış olan birçok deneysel çalışmada diyabetik dokularda ROS miktarının aşırı düzeyde arttığı gösterilmiştir (24,38,43). ROS, fizyolojik koşullar altında bile serbest oksijen radikalleri, hidrojen peroksit, nitrik oksit (NO) ve peroksinitrit gibi bir dizi kimyasal reak- (51).…”

“…Farklı dokularda diyabet indüklü anormalliklerde, reaktif oksijen türlerinin (ROS) önemli bir role sahip olduğunu gösteren kanıtlar her geçen gün artmaktadır (10,(35)(36)(37)(38). Losartan, antioksidan savunma sistemini güçlendirerek ROS'nin artışını engelleyebilir.…”