Biomaterial Database

Genotoxic, biochemical and histopathological studies to assessment the topiramate hepatorenal toxicity in mice. 2022

Aida I El Makawy, and Dalia M Mabrouk, and Faten M Ibrahim, and Kawkab A Ahmed

Cell Biology Department, National Research Center, Giza, Egypt.

Liver and kidney role in detoxification and drug metabolism increases the risk of their poisonous injury. Topiramate (TMP) is an effective popular migraine prophylaxis that is accepted for utilize in adults and teenagers. Therefore, the target of this research is to estimate the potential toxic effects of TMP on liver and kidney in male mice. Thirty-two adult albino male mice were divided into four groups (n = 8 mice). Group I of animals was given saline solution and used as negative control. The other three groups were administrated TPM at doses (100, 200 and 400 mg/kg) for 28 days. Genotoxicity was evaluated by comet assay and DNA fragmentation by Diphenyleamine. Biochemical investigation was achieved by estimating liver enzymes (AST, ALT), alkaline phosphatase (ALP) creatinine and uric acid. In addition, measurement of the antioxidant enzymes, malondialdehyde and nitric oxide were performed in both two tissues of liver and kidney. Microscopic examination of hematoxyline and eosin (H&E), tumor necrosis factor (TNF-α) and caspase3 stained sections were done to explore the effect of topiramate on mice tissues of liver and kidney. The data revealed that TPM showed dose dependent toxicity that represented in: DNA damage in tested cells and increased level of liver enzymes, creatinine and uric acid as markers of toxicity. Topiramate significantly diminished antioxidant enzymes activities and elevated the level of malondialdehyde and nitric oxide. In addition, TPM caused histopathological alterations and dose dependent positive immune reaction for TNF--α and caspase 3 in kidney and liver tissues. The results showed that Topiramate has marked toxicity in liver and kidney of mice.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D000077236	Topiramate	A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of EPILEPSY and MIGRAINE DISORDERS, and may also promote weight loss.	2,3-4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate,Epitomax,McN 4853,McN-4853,Topamax,USL255,McN4853
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018384	Oxidative Stress	A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).	Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative