COMPARATIVE NEPHROTOXICITY EVALUATION OF LEVETIRACETAM AND TOPIRAMATE AS SINGLE AND COMBINED DRUG ADMINISTRATION IN RATS
Main Article Content
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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Sultan Saad AlGhamdi
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia.
Syed Imam Rabbani
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia.
Ahmad H. Alhowail
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia.
Shahad Rajeh AlGhaamdi
Clinical Pharmacy intern at King Fahad Hospital, Kingdom of Saudi Arabia, Baha city
Raneem Ali AlGhamdi
Clinical Pharmacy intern at King Fahad Hospital, Kingdom of Saudi Arabia, Baha city
Khalid Abdullah AlZahrani
Clinical Pharmacy intern at Al-Nahdi Community Pharmacy #7368, Kingdom of Saudi Arabia, Baha city
Abdulsalam Saleh AlZahrani
Clinical Pharmacy intern at Al-Nahdi Community Pharmacy #1002, Kingdom of Saudi Arabia, Jeddah city
Alya Saeed AlGhamdi
Clinical Pharmacy intern at King Fahad Hospital, Kingdom of Saudi Arabia, Baha city
Mohammed Faisal Alzahrani
Clinical Pharmacy intern at Al-Dawa Community Pharmacy #977 , Kingdom of Saudi Arabia, Makka city