Yusuf Olgar

Trace elements in diabetic cardiomyopathy: An electrophysiological overview.

There is a growing body of evidence that Diabetes Mellitus leads to a specific cardiomyopathy apart from vascular disease and bring about high morbidity and mortality throughout the world. Recent clinical and experimental studies have extensively demonstrated that this cardiomyopathy causes impaired cardiac performance manifested by early diastolic and late systolic dysfunction. This impaired cardiac performance most probably have emerged upon the expression and activity of regulatory proteins such as Na(+)/Ca(2+) exchanger, sarcoplasmic reticulum Ca(2+)-ATPase, ryanodine receptor and phospholamban. Over years many therapeutic strategies have been recommended for treatment of diabetic cardiomyopathy. Lately, inorganic elements have been suggested to have anti-diabetic effects due to their suggested ability to regulate glucose homeostasis, reduce oxidative stress or suppress phosphatases. Recent findings have shown that trace elements exert many biological effects including insulin-mimetic or antioxidant activity and in this manner they have been recommended as potential candidates for treatment of diabetes-induced cardiac complications, an effect based on their modes of action. Some of these trace elements are known to play an essential role as component of enzymes and thus modulate the organ function in physiological and pathological conditions. Besides, they can also manipulate redox state of the channels via antioxidant properties and thus contribute to the regulation of [Ca(2+)]i homeostasis and cardiac ion channels. On account of little information about some trace elements, we discussed the effect of vanadium, selenium, zinc and tungstate on diabetic heart complications.

Changes of auditory event-related potentials in ovariectomized rats injected with d-galactose: Protective role of rosmarinic acid

HIGHLIGHTSOvariectomy alone and with d‐galactose treatment affected the auditory processing.Estrogen deficiency and d‐galactose induce lipid peroxidation.Rosmarinic acid reversed the AERP/MMN alterations in OVX d‐galactose injected rats. ABSTRACT Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful agent for protecting central nervous system against age related alterations. In this context, the purpose of the present study was to investigate possible protective effects of RA on mismatch negativity (MMN) component of auditory event‐related potentials (AERPs) as an indicator of auditory discrimination and echoic memory in the ovariectomized (OVX) rats injected with d‐galactose combined with neurochemical and histological analyses. Ninety female Wistar rats were randomly divided into six groups: sham control (S); RA‐treated (R); OVX (O); OVX + RA‐treated (OR); OVX + d‐galactose‐treated (OD); OVX + d‐galactose + RA‐treated (ODR). Eight weeks later, MMN responses were recorded using the oddball condition. An amplitude reduction of some components of AERPs was observed due to ovariectomy with or without d‐galactose administiration and these reduction patterns were diverse for different electrode locations. MMN amplitudes were significantly lower over temporal and right frontal locations in the O and OD groups versus the S and R groups, which was accompanied by increased thiobarbituric acid reactive substances (TBARS) and hydroxy‐2‐nonenal (4‐HNE) levels. RA treatment significantly increased AERP/MMN amplitudes and lowered the TBARS/4‐HNE levels in the OR and ODR groups versus the O and OD groups, respectively. Our findings support the potential benefit of RA in the prevention of auditory distortion related to the estrogen deficiency and d‐galactose administration at least partly by antioxidant actions.

Rho-kinase inhibition reverses impaired Ca2+ handling and associated left ventricular dysfunction in pressure overload-induced cardiac hypertrophy

Recent studies have implicated a relationship between RhoA/ROCK activity and defective Ca2+ homeostasis in hypertrophic hearts. This study investigated molecular mechanism underlying ROCK inhibition-mediated cardioprotection against pressure overload-induced cardiac hypertrophy, with a focus on Ca2+ homeostasis. Cardiac hypertrophy model was established by performing transverse aortic constriction (TAC) in 8-week-old male rats. Groups were assigned as SHAM, TAC and TAC+Fas (rats undergoing TAC and treated with fasudil). Rats in the TAC+Fas group were administered fasudil (5mg/kg/day), and rats in the SHAM and TAC groups were treated with vehicle for 10 weeks. Electrophysiological recordings were obtained from isolated left ventricular myocytes and expression levels of proteins were determined using western blotting. Rats in the TAC group showed remarkable cardiac hypertrophy, and fasudil treatment significantly reversed this alteration. TAC+Fas myocytes showed significant improvement in reduced contractility and Ca2+ transients. Moreover, these myocytes showed restoration of slow relaxation rate and Ca2+ reuptake. Although L-type Ca2+ currents did not change in TAC group, there was a significant reduction in the triggered Ca2+ transients which was reversed either by long-term fasudil treatment or incubation of TAC myocytes with fasudil. The hearts of rats in the TAC group showed a significant decrease in ROCK1, ROCK2, RyR2 protein levels and p-PLBS16/T17/SERCA2 ratio and increase in RhoA expression and MLC phosphorylation. However, fasudil treatment largely reversed TAC-induced alterations in protein expression. Thus, our findings indicate that upregulation of the RhoA/ROCK pathway is significantly associated with cardiac hypertrophy-related Ca2+ dysregulation and suggest that ROCK inhibition prevents hypertrophic heart failure.

2.1 GHz electromagnetic field does not change contractility and intracellular Ca2+ transients but decreases β-adrenergic responsiveness through nitric oxide signaling in rat ventricular myocytes

Purpose: Due to the increasing use of wireless technology in developing countries, particularly mobile phones, the influence of electromagnetic fields (EMF) on biologic systems has become the subject of an intense debate. Therefore, in this study we investigated the effect of 2.1 GHz EMF on contractility and beta-adrenergic (β-AR) responsiveness of ventricular myocytes. Materials and methods: Rats were randomized to the following groups: Sham rats (SHAM) and rats exposed to 2.1 GHz EMF for 2 h/day for 10 weeks (EM-10). Sarcomere shortening and Ca2+ transients were recorded in isolated myocytes loaded with Fura2-AM and electrically stimulated at 1 Hz, while L-type Ca2+ currents (ICaL) were measured using whole-cell patch clamping at 36 ± 1°C. Cardiac nitric oxide (NO) levels were measured in tissue samples using a colorimetric assay kit. Results: Fractional shortening and amplitude of the matched Ca2+ transients were not changed in EM-10 rats. Although the isoproterenol-induced (10−6 M) ICaL response was reduced in rats exposed to EMF, basal ICaL density in myocytes was similar between the two groups (p < 0.01). Moreover, EMF exposure led to a significant increase in nitric oxide levels in rat heart (p < 0.02). Conclusions: Long-term exposure to 2.1 GHz EMF decreases β-AR responsiveness of ventricular myocytes through NO signaling.

Onset of Depressed Heart Work is Correlated with the Increased Heart Rate and Shorten QT-Interval in High-Carbohydrate Fed Overweight Rats

Mechanical activity of the heart is adversely affected in metabolic syndrome (MetS) characterized by increased body mass and marked insulin resistance. Herein, we examined the effects of high carbohydrate intake on cardiac function abnormalities by evaluating in situ heart work, heart rate, and electrocardiograms (ECGs) in rats. MetS was induced in male Wistar rats by adding 32% sucrose to drinking water for 22-24 weeks and was confirmed by insulin resistance, increased body weight, increased blood glucose and serum insulin, and increased systolic and diastolic blood pressures in addition to significant loss of left ventricular integrity and increased connective tissue around myofibrils. Analysis of in situ ECG recordings showed a markedly shortened QT interval and decreased QRS amplitude with increased heart rate. We also observed increased oxidative stress and decreased antioxidant defense characterized by decreases in serum total thiol level and attenuated paraoxonase and arylesterase activities. Our data indicate that increased heart rate and a shortened QT interval concomitant with higher left ventricular developed pressure in response to β-adrenoreceptor stimulation as a result of less cyclic AMP release could be regarded as a natural compensation mechanism in overweight rats with MetS. In addition to the persistent insulin resistance and obesity associated with MetS, one should consider the decreased heart work, increased heart rate, and shortened QT interval associated with high carbohydrate intake, which may have more deleterious effects on the mammalian heart.