Histological Assessment of the Effect of Lacosamide on the Kidney Tissue of Pregnant Albino Rats

Epilepsy is a common disorder affecting approximately more
than 1.000.000 women in fertile period...


Introduction
Epilepsy is a common disorder affecting approximately more than 1.000.000 women in fertile period [1]. The prevalence of epilepsy was estimated to be 0.4 % in pregnant women [2]. Pregnant women with epilepsy are advised to maintain Antiepileptic Drugs (AED) [3]. Pharmacological treatment options of epilepsy comprise conventional AED (valproate) and second-generation agents (Lacosamide) [4]. Some undesired effects associated with conventional AED, such as Stevens-Johnson syndrome and memory deterioration [5]. The effectiveness of the second generation drugs, seems to be similar to that of the conventional AED. However, the second-generation drugs, offer a lower risk of interactions with other medications, simpler titration and improved tolerability [4].
Lacosamide was developed as an analogue of piracetam, a drug used to improve cognitive function [6]. it is recognized for adjunct therapy of focal onset in children and adults [7].
Peak plasma concentrations of the drug in 1.3 hours. Twothirds of the drug is excreted in the urine [8]. Studies reported adverse effects associated with Lacosamide therapy e.g. vomiting, irritability, headaches, inflammation of the nose and throat, and sleepiness [9]. Data on the adverse effects of Lacosamide during pregnancy is still limited [10]. So, this work aimed to assess the effect of Lacosamide on kidney of pregnant albino rats.

Materials and Methods
Lacosamide was available in the form of tablets 500 mg each.
The chosen dose for adult humans was 2000mg/day. The equivalent dose for adult rat weighting about 200 gm is 36 mg/day [11].
The forty pregnant rats were divided equally into two groups: a) Group I (control): received 1.5 ml/day distilled water in two divided doses throughout pregnancy. b) Group II (treated): received 1.5 ml/day distilled water (containing 36 mg Lacosamide) in two divided doses throughout pregnancy.
At the end of the experiment,

1.
Blood samples were collected [12]. The sera were separated then preserved at − 20°C for biochemical analysis.

2.
Rats were sacrificed then kidneys were excised and used for: A.
Lght microscopy Sections were stained with I. Hematoxylin and Eosin to study the general histological features of selected kidney tissue.
II. Immunohistochemistry, anti-bovine type IV (collagen rabbit serum was used as first antibody, and biotinylated antirabbit Iggy goat serum was used as secondary antibody) B. Electron microscopic examination.

Biochemical Results: Statistical analysis of the mean levels of
Urea and creatinine in groups I and II revealed significant increase in group II as compared with group I (P< 0.05) ( Table 1).

Discussion
The current research revealed that administration of  [16]. On the other hand, the results of the current study were antithesis to other researchers who didn't detect major side effects any patients after use of intravenous Lacosamide in patients with renal impairment [17]. The results of the present study also were contrary to another study, the authors presented two pediatric cases of Lacosamide overdose for one month and didn't observe severe side effects in the patients. So, they suggested that accidental treatment with an overdose of Lacosamide in children for long period was not accompanied with serious side effects [18].
In the current study, the degenerative changes that were observed in the and kidney might be due to disturbance in the oxidant/antioxidant ratio. Such suggestion was supported by researchers [19][20][21][22][23] who explained that genotoxic potential of Lacosamide by decreased free radical neutralization and/or an increased production of free radicals.Other researcher reported that, relationship between serum lacosamide concentrations and clinical efficacy is not well understood; thus, therapeutic drug monitoring is not routinely recommended [24][25][26][27]. Yet, we demonstrated that measuring serum lacosamide concentrations in the critically ill population during continuous renal replacement therapy may be useful to individualize dosing programs [28][29][30][31][32][33][34]. Further pharmacokinetic studies of lacosamide may be necessary to generate widespread dosing recommendations [5]. Mahmoud

SH reported that Continuous Renal Replacement Therapy (CRRT)
is used for managing acute kidney injury in critically ill patients [35][36][37]. Removal of Antiepileptic Drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay [11]. Other researcher reported that additional studies are necessary before specific dosing recommendations can be made for

Conclusion
Authors concluded that Lacosamide induced dangerous effects on the kidney of pregnant albino rats. Continuous assessment of the kidney functions during Lacosamide therapy is advised. In addition, further investigations are recommended to clarify the mechanism of Lacosamide toxicity [38].

Funding Details
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.