Pharmacology
Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats

https://doi.org/10.1016/j.jtemb.2011.09.003Get rights and content

Abstract

As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180–200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10 mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24 h after the last injection. Blood samples were collected and serum was separated and stored at −20 °C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P < 0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats.

Introduction

Sildenafil citrate (C22H30N8O4S)

Sildenafil is a selective inhibitor of phosphodiestrase-5 (PDE-5) and thus effectively slowing the degradation of guanosine 3,5-cyclic monophosphate (C GMP), the second messenger in the nitric oxide (NO) signaling pathway. As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases [1]. Sildenafil selectively inhibiting PDE-5 present in the endothelium of the corpora cavernosa and prolongs the relaxation of the pericavernous smooth muscle, sustaining its engorgement with blood and subsequently improve the erectile dysfunction [2]. Sildenafil was successfully used in a rat model of brain ischemia after embolic stroke and was found to augment neurogenesis in the subventricular zone in aged, ischemic rats with reduced number of neural progenitors [3], [4], [5]. PDE-5 was reported to be found in platelets, skeletal muscle, and vesicular and pulmonary vascular smooth muscle, as well as in cerebral neurons and vessels [6], [7]. Inhibition of PDE-5 in the brain would enhance and prolong the local effect of NO causing vasodilatation of cerebral blood vessels [8]. Trace elements, such as zinc (Zn), Copper (Cu), iron (Fe), selenium (Se) and chromium (Cr) are necessary for the growth and function of the brain that deficiency or excess of these elements resulted in nervous system disorders [9]. The transport of trace elements into the brain is strictly regulated by the brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers. Trace elements usually serve the function of metalloproteins in neurons and glial cells, while portion of these elements exist in the presynaptic vesicles and may be released with neurotransmitters into the synaptic cleft [10]. Zinc has been reported to protect the blood brain barrier (BBB) against oxidative stress and prevent the development of neurological disorders [11]. Iron is essential as a cofactor in the synthesis of neurotransmitters and myelin [12] and its deficiency leads to decreased learning capacity [13]. Copper is essential for biosynthesis of neurotransmitters which play a modulatory role in the CNS function [14]. Selenium was found in considerable levels in different brain regions of male rats such as cerebellum, hypothalamus, and hippocampal tissues [15]. Selenium was reported to prevent excitotoxic brain damage, brain ischemia and improve mood, cognitive function, and clarity [16], [17]. Chromium has been reported to improve glucose utilization by neural cells however; Cr excess induced a negative impact on the endocrine function of the hypothalamus and anterior pituitary gland [18].

The objective of the present work was to determine the effect of sildenafil citrate on serum and brain trace elements (Zn, Cu, Fe, Se, Co, and Cr) concentration of rats.

Section snippets

Materials and methods

This study was conducted on 16 healthy male albino rats weighing 180–200 g. Rats were divided into two groups (8 rats/group) and housed in wired cages, and food and water were provided ad libitum. All requirements of local animals care committees were adhered to. Rats in the first group (control) were administered 0.5 ml saline (0.9% NaCl) i.p. every 72 h for 12 injections. Rats in the second group (sildenafil) were administered sildenafil citrate (Viagra®, Pfizer Inc. USA) at a dose of 10 mg/kg

Results

Trace element concentrations in the serum of control and sildenafil treated rats are shown in Table 1. The results showed that Se concentration was the highest trace element (428.4 μg/dl and Co was the lowest (12.0 μg/dl). Administration of sildenafil has no significant effect on serum Zn, Fe, Co, and Cr concentrations. However, the concentration of serum Se and Cu were significantly increased (P < 0.05) in rats treated with sildenafil.

Trace element concentrations of the brain in the control and

Discussion

The concentration of trace elements in the blood and different organs reflects the physiological importance of these elements on body function or the exposure of living creatures to environmental pollution {9,22]. One area of growing interest is the role of PDE-5 inhibitors and NO release from a variety of cells on several biological processes. The present study showed that selective inhibition of PDE-5 by sildenafil induced a significant increase in serum and brain Cu and Se concentration.

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