Abstract
BackgroundThe observed controversy that N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211), a selective serotonin (5-HT7) receptor agonist, may either modify or exacerbate imbalances in serum electrolyte concentrations and renal tissue of spinal cord trauma cases has not been reported yet. The aim of this study was to better understand the effects of a new 5-HT7 receptor agonist, LP-211, on serum electrolyte changes in spinal cord injured- (SCI) rats.MethodsSixty male rats were assigned to the following groups: A) Intact (saline as vehicle, 1 ml/kg, i.p.), B) Intact [LP-211, (0.003–0.3 mg/kg, i.p.)], C) Sham-operated [laminectomy + vehicle (1 ml/kg, i.p.)], D) Sham-operated [laminectomy + LP-211 (0.003–0.3 mg/kg, i.p.)], E) Treatment [laminectomy + spinal trauma (SCI) + vehicle (1 ml/kg, i.p.)], F) Treatment [laminectomy + spinal trauma + LP-211 (0.003–0.3 mg/kg, i.p.)]. SCI was performed by placing an aneurysm clip, extradurally at the level of T10. After two weeks, LP-211 was administered cumulatively and each dose was injected (i.p.) with 20 min interval. At the end of the experiment, blood samples were collected for biochemical evaluations of the electrolytes employing standard commercial kits.ResultsThe present results indicate elevated serum levels of Na+, K+, and Mg2+ in SCI rats and significant differences demonstrated between the groups [P < 0.001, F(5, 35) = 23.92], [P < 0.001, F(5, 35) = 67.63], [P < 0.001, F(5, 35) = 71.144], respectively. So that, in groups B, D and F, there was a significant increase in K+ and Mg2+ serum levels compared to the groups A, C, and E (P < 0.001). Furthermore, Na+ serum levels in SCI (LP-211), laminectomy (LP-211), and intact (LP-211) groups tended to be statistically lower than SCI (saline), laminectomy (saline) and intact (saline) groups. Infact, hyponatremia, hyperkalemia and hypermagnesemia was obtained in group F. Nevertheless, in the remaining measured serum electrolytes such as calcium (Ca2+), iron (Fe2+) and phosphorus (P3−), chlorine (Cl−), copper (Cu+), and zinc (Zu+), no significant changes were observed.ConclusionIt was shown that acute additive LP-211 treatments in the SCI group led to hyponatremia, hyperkalemia and hypermagnesemia, it may be stated that LP-211 treatment as a promising candidate for treating SCI complications in some systems especially urinary tract might take into consideration and further studies would be needed to clarify its benefits or drawbacks. The observed discrepancies, nevertheless; will also pose new questions. Altogether, this will ultimately contribute to further understanding the pathophysiological role regarding 5-HT7 receptor activation.
Highlights
The Na+-K+ pump is a ubiquitous membrane proteinTraumatic spinal cord injury (SCI) is a major clinical problem with permanent neurological deficits and a broad range of secondary complications [1]
E Results: The present results indicate elevated serum levels of Na+, K+, and Mg2+ in SCI rats and significant differences demonstrated between the groups [P < 0.001, F(5, 35) = 23.92], [P < 0.001, F(5, 35) = 67.63], [P < 0.001, F(5, 35) = 71.144], respectively
Na+-K+ pump activity is regulated by a variety of horphysiology of acute SCI involving primary and secondary mones, neurotransmitters, and growth factors. 5-HT, in mechanisms of injury is highly complex and not clearly particular, activates the Na+-K+ pump in the brain [28], understood
Summary
The Na+-K+ pump is a ubiquitous membrane proteinTraumatic spinal cord injury (SCI) is a major clinical problem with permanent neurological deficits and a broad range of secondary complications [1]. 5-HT, in mechanisms of injury is highly complex and not clearly particular, activates the Na+-K+ pump in the brain [28], understood. Primary events occur at the time of trauma and related to mechanical damage and after primary injury, further pathophysiological processes such as hypoxia, edema and inflammation, altered blood flow and changes in microvascular permeability are triggered; lesions greatly enlarge and worsen by secondary injury [2, 3]. Several studies have revealed that one consequence of trauma to the spinal cord is an increase in lipid peroxidation and a decrease in the activity of the critical membrane-bound enzymes such as Na+-K+-activated ATPase and Na+-K+/Mg+2 ATPase [7,8,9,10]
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