Investigation of the Effect of Circadian Changes on Phenytoin-Induced Hepatotoxicity in Rats
Authors
-
Shima Mohammadi
- Neuroscience Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.- Department of Neuroscience, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
https://orcid.org/0000-0001-5199-5958
- Zahra Ghanbari - Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
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Hossein Khastar
- School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
https://orcid.org/0000-0003-0553-3757
-
Behzad Garmabi
- Neuroscience Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. - Department of Neuroscience, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
https://orcid.org/0000-0001-8228-0250
DOI:
https://doi.org/10.22100/jkh.v20i1.3411Keywords:
Circadian, Hepatotoxicity, Phenytoin, Cytochrome P450, RatAbstract
Introduction: Circadian rhythms are 24-hour cycles that regulate physiological processes and contribute to homeostasis. Cytochrome P450, which is involved in the hepatic metabolism of phenytoin, is influenced by these rhythms. This study investigates the effect of circadian rhythms on phenytoin-induced liver toxicity.
Methods: Twenty-five Wistar rats (180–220 g) were divided into five groups. Four groups received phenytoin (50 mg/kg) at different times (8 a.m., 12 p.m., 4 p.m., and 8 p.m.) for five days, while the control group received normal saline. Twenty-four hours after the last injection, plasma levels of SGPT, SGOT, ALP, and GGT enzymes were measured.
Results: Phenytoin significantly increased the levels of SGPT, SGOT, ALP, and GGT compared to the control group, indicating liver damage. Comparison across different injection times showed that the impact of timing on GGT and SGOT was more pronounced than on ALP and SGPT. Changes in GGT, ALP, and SGOT levels were significant, whereas SGPT levels showed no statistically significant difference.
Conclusion: The results suggest that phenytoin-induced hepatotoxicity is time-dependent. This highlights the importance of considering circadian rhythms in adjusting the dose and timing of drug administration, as it may help reduce side effects and optimize drug efficacy.
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