COMPARATIVE NEPHROTOXICITY EVALUATION OF LEVETIRACETAM AND TOPIRAMATE AS SINGLE AND COMBINED DRUG ADMINISTRATION IN RATS

Main Article Content

Sultan Saad AlGhamdi
Syed Imam Rabbani
Ahmad H. Alhowail
Shahad Rajeh AlGhaamdi
Raneem Ali AlGhamdi
Khalid Abdullah AlZahrani
Abdulsalam Saleh AlZahrani
Alya Saeed AlGhamdi
Mohammed Faisal Alzahrani

Keywords

Drug toxicity, Renal impairment, Levetiracetam, Topiramate, Antioxidant, Antiepileptic

Abstract

Background: The antiepileptic medications used to treat seizures are known to produce several dose-dependent complications including renal impairment. The present study aims to evaluate the role of levetiracetam (LEVE) and topiramate (TOPI) on the renal impairment when used either alone or combination in sub-maximal doses in rats.


Methods: Twenty-four adult male Sprague Dawley rats were utilized in the study. Six randomly selected rats were grouped such as group-A (control, normal saline), group-B (TOPI, 400 mg/kg), group-C (LEVE, 600 mg/kg), group-D (combination of LEVE and TOPI) and were treated orally for 21 days. Blood samples were collected under light chloroform anesthesia from retro-orbital plexus and serum was subjected to biochemical estimation. The markers of apoptosis (caspase-3), acute renal damage (neutrophil gelatinoase associated lipocalin, NGAL), antioxidant status [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase-1 (Gpx-1)] and relative kidney weight were estimated. The data was statistically compared by one-way ANOVA and p-value less than 0.05 was used to indicate the significance of results.


Results: The analysis of data suggested that both TOPI and LEVE significantly (p<0.001) enhanced the caspase-3, NGAL levels and relative kidney weight compared to control group. The combination of these agents was found to enhance further these variations in rats. The MDA level was observed to be enhanced (p<0.001) by both TOPI and LEVE, while CAT, SOD and Gpx-1 were diminished (p<0.001) compared to control. In addition, TOPI and LEVE augmented these changes in antioxidant status when administered in combination.


Conclusion: The results suggest that the sub-maximal doses of TOPI and LEVE might produce renal impairment and use of these in combination could potentiate the renal toxicity. Compromised antioxidant status appears to be the cause for enhanced caspase-3 and NGAL levels. Data indicates caution while utilizing these drugs in patients, especially while treating at higher doses.

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