Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques

Kamil, Kamil; Fatima, Arifa; Ullah, Sami; Ali, Gowhar; Khan, Rasool; Ismail, Naila; Qayum, Mughal; Irimie, Marius; Dinu, Catalina Georgeta; Ahmedah, Hanadi Talal; Cocuz, Maria-Elena

doi:10.3390/toxics9060119

Cited by 4 publications

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References 61 publications

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“…These observations included physical motor activity (movement), body appearance in different positions, such as sitting or standing, and behavioral interactions (interactions with cage mates and nesting). These observations were made throughout the acute experimental study on a daily basis [ 90 ].…”

Section: Methodsmentioning

confidence: 99%

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Synthesis, Molecular Docking, and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective, Hepatoprotective and Lipid-Lowering Effects

et al. 2022

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Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = −7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = −7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

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Section: Methodsmentioning

confidence: 99%

“…Molecular Operating Environment (MOE 2016.0802) was used for carrying out the docking studies [ 90 ]. Docking studies were carried out on enzyme obtained from the Protein Data Bank (PDB), with 6KZP and 2RH1 accession codes, respectively.…”

Section: Methodsmentioning

confidence: 99%