Cardioprotective effects of amiodarone in a rat model of epilepsy-induced cardiac dysfunction.

Cardiac dysfunction is one of the leading causes of death in epilepsy. The anti-arrhythmic drug, amiodarone, is under investigation for its therapeutic effects in epilepsy. We aimed to evaluate the possible effects of amiodarone on cardiac injury during status epilepticus, as it can cause prolongation of the QT interval. Five rat groups were enrolled in the study; three control groups (1) Control, (2) Control-lithium and (3) Control-Amio, treated with 150 mg/kg/intraperitoneal amiodarone, (4) Epilepsy model, induced by sequential lithium/pilocarpine administration, and (5) the epilepsy-Amio group. The model group expressed a typical clinical picture of epileptiform activity confirmed by the augmented electroencephalogram alpha and beta spikes. The anticonvulsive effect of amiodarone was prominent, it diminished (p < 0.001) the severity of seizures and hence, deaths and reduced serum noradrenaline levels. In the model group, the electrocardiogram findings revealed tachycardia, prolongation of the corrected QT (QTc) interval, depressed ST segments and increased myocardial oxidative stress. The in-vitro myocardial performance (contraction force and - (df/dt)max ) was also reduced. Amiodarone decreased (p < 0.001) the heart rate, improved ST segment depression, and myocardial contractility with no significant change in the duration of the QTc interval. Amiodarone preserved the cardiac histological structure and reduced the myocardial injury markers represented by serum Troponin-I, oxidative stress and IL-1. Amiodarone pretreatment prevented the anticipated cardiac injury induced during epilepsy. Amiodarone possessed an anticonvulsive potential, protected the cardiac muscle and preserved its histological architecture. Therefore, amiodarone could be recommended as a protective therapy against cardiac dysfunction during epileptic seizures with favourable effect on seizure activity.

Vitamin D Supplementation Improves Uterine Receptivity in a Rat Model of Vitamin D Deficiency: A Possible Role of HOXA-10/FKBP52 Axis.

Synchronized uterine receptivity with the time of implantation is crucial for pregnancy continuity. Vitamin D (VD) deficiency has been linked to the failure of implantation. Therefore, we tested the link between the Homeobox transcription factor-10/immunophilin FK506-binding protein 52 (HOXA-10/FKBP52) axis and the uterine receptivity in VD-deficient rats. The effect of VD supplementation at different doses was also investigated. Forty-eight pregnant rats were divided into six groups (eight/group); normal control rats fed with standard chow (control), control rats supplemented with VD (equivalent dose of 400 IU/day) (control-D400). VD-deficient group (DEF) and the three VD deficiency groups with VD supplementation were equivalent to 400, 4,000, and 10,000 IU/day (DEF-D400, DEF-D4000, and DEF-D10000, respectively). The expression levels of HOXA-10/FKBP52, progesterone level, and histological evaluation of decidualization using osteopontin (OSN) and progesterone receptor (PGR) were estimated. An assessment of the uterine contractility was conducted for all rats. This study showed the downregulation of HOXA-10/FKBP52 together with increased amplitude and frequency of the uterine contractility in the DEF group compared to control. VD dose-dependent supplementation restored progesterone/receptor competency, upregulated the expressional response of HOXA-10 and its downstream FKBP52, and improved uterine receptivity and endometrial decidualization at the time of implantation that was documented by increased area% of OSN and the number of implantation beads.

Graphene Oxide-Gold Nanosheets Containing Chitosan Scaffold Improves Ventricular Contractility and Function After Implantation into Infarcted Heart.

Abnormal conduction and improper electrical impulse propagation are common in heart after myocardial infarction (MI). The scar tissue is non-conductive therefore the electrical communication between adjacent cardiomyocytes is disrupted. In the current study, we synthesized and characterized a conductive biodegradable scaffold by incorporating graphene oxide gold nanosheets (GO-Au) into a clinically approved natural polymer chitosan (CS). Inclusion of GO-Au nanosheets in CS scaffold displayed two fold increase in electrical conductivity. The scaffold exhibited excellent porous architecture with desired swelling and controlled degradation properties. It also supported cell attachment and growth with no signs of discrete cytotoxicity. In a rat model of MI, in vivo as well as in isolated heart, the scaffold after 5 weeks of implantation showed a significant improvement in QRS interval which was associated with enhanced conduction velocity and contractility in the infarct zone by increasing connexin 43 levels. These results corroborate that implantation of novel conductive polymeric scaffold in the infarcted heart improved the cardiac contractility and restored ventricular function. Therefore, our approach may be useful in planning future strategies to construct clinically relevant conductive polymer patches for cardiac patients with conduction defects.

Vitamin D protection from rat diabetic nephropathy is partly mediated through Klotho expression and renin-angiotensin inhibition.

OBJECTIVE: We hypothesised that vitamin D has a beneficial renal protective effect from diabetic nephropathy (DN). METHODS: Four rat groups were included: normal control (control), type 2 diabetes for eight weeks (DM), treated group with angiotensin receptor blocker losartan (DM + L), and vitamin D-treated group started from the onset of diabetes (DM + Vit D). RESULTS: In the both treated groups, we found a significant (p < .05) reduction in the renal pro-inflammatory and profibrotic markers induced by diabetes. Vitamin D caused more reduction in monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGFß-1), and renin-angiotensin levels that gave better kidney function compared to the DM + L group. CONCLUSION: Vitamin D may have a valuable role in the renal protective effect from DN, this may occur via expression of its VDR, Klotho and blocking renin-angiotensin activation, so vitamin D should be considered as a target in renal prophylactic measures against DN.