Trimetazidine protects against acute indomethacin-induced gastric mucosal, hepatic, and renal injury in rats

Background: Peptic ulcers are increasingly reported as a challenging disease in clinical settings. Several medications are employed in the management of peptic ulcers. Thus far, there is no medication devoid of any adverse effects that may achieve a 100% curative rate or provide a total remedy for the ailment. Aim: We aimed to examine the healing effects of trimetazidine against indomethacin-induced gastric ulcers in albino rats. Methodology: A total of 25 rats were used, divided into five groups (each group contained five rats): a negative control group that was only treated with distilled water, a positive control group that was only treated with a single dose of indomethacin (30 mg/kg) orally, a group that received indomethacin (30 mg/kg) and low doses of trimetazidine (17.5 mg/kg) orally, a group that received indomethacin (30 mg/kg) and medium doses of trimetazidine (35 mg/kg) orally, and a group that received indomethacin (30 mg/kg) and high doses of trimetazidine (52.5 mg/kg) orally. The induction of gastric ulcers occurred on the first day of the experiment through the administered indomethacin and, subsequently, the rats were treated orally with either trimetazidine or distilled water, three times daily, for 7 days. Serum urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels were measured. Stomachs were excised from the rats’ bodies and opened along the greater curvature; they were then rinsed with saline, extended on a white corkboard, and examined macroscopically. The stomach tissues were also processed in order to generate microscopic slides for microscopical examination. Results: Indomethacin administration caused multiple ulcerations in the gastric mucosa, significant elevations in serum urea, creatinine, AST, and ALT levels, and a significant reduction of the serum albumin levels. The treatment with trimetazidine significantly healed the indomethacin-induced gastric ulcers. Conclusion: The present study indicates that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin can induce substantial gastric ulcers, which may be linked to a direct toxic effect on the histological architecture of the gastric linings in addition to the reduction of blood flow to gastric mucosa; this effect can be treated by administration of trimetazidine. Ultimately, this study suggests that administering the optimal dosage of trimetazidine can be advantageous in treating stomach ulcers caused by NSAIDs. Moreover, the study suggests that the indomethacin-induced liver and renal dysfunction can also be alleviated by the use of trimetazidine.

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Publication Details

Journal
Review of Clinical Pharmacology and Pharmacokinetics - International Edition
Published
2024-10-07
DOI
https://doi.org/10.61873/dspq4535
Primary Topic
Antibiotics Pharmacokinetics and Efficacy
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article
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article

Trimetazidine protects against acute indomethacin-induced gastric mucosal, hepatic, and renal injury in rats

Zeina A. Althanoon, Momenah M. Yahya
Review of Clinical Pharmacology and Pharmacokinetics - International Edition
Antibiotics Pharmacokinetics and Efficacy
article

Trimetazidine protects against acute indomethacin-induced gastric mucosal, hepatic, and renal injury in rats

Zeina A. Althanoon, Momenah M. Yahya
article en

Abstract

Background: Peptic ulcers are increasingly reported as a challenging disease in clinical settings. Several medications are employed in the management of peptic ulcers. Thus far, there is no medication devoid of any adverse effects that may achieve a 100% curative rate or provide a total remedy for the ailment. Aim: We aimed to examine the healing effects of trimetazidine against indomethacin-induced gastric ulcers in albino rats. Methodology: A total of 25 rats were used, divided into five groups (each group contained five rats): a negative control group that was only treated with distilled water, a positive control group that was only treated with a single dose of indomethacin (30 mg/kg) orally, a group that received indomethacin (30 mg/kg) and low doses of trimetazidine (17.5 mg/kg) orally, a group that received indomethacin (30 mg/kg) and medium doses of trimetazidine (35 mg/kg) orally, and a group that received indomethacin (30 mg/kg) and high doses of trimetazidine (52.5 mg/kg) orally. The induction of gastric ulcers occurred on the first day of the experiment through the administered indomethacin and, subsequently, the rats were treated orally with either trimetazidine or distilled water, three times daily, for 7 days. Serum urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels were measured. Stomachs were excised from the rats’ bodies and opened along the greater curvature; they were then rinsed with saline, extended on a white corkboard, and examined macroscopically. The stomach tissues were also processed in order to generate microscopic slides for microscopical examination. Results: Indomethacin administration caused multiple ulcerations in the gastric mucosa, significant elevations in serum urea, creatinine, AST, and ALT levels, and a significant reduction of the serum albumin levels. The treatment with trimetazidine significantly healed the indomethacin-induced gastric ulcers. Conclusion: The present study indicates that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin can induce substantial gastric ulcers, which may be linked to a direct toxic effect on the histological architecture of the gastric linings in addition to the reduction of blood flow to gastric mucosa; this effect can be treated by administration of trimetazidine. Ultimately, this study suggests that administering the optimal dosage of trimetazidine can be advantageous in treating stomach ulcers caused by NSAIDs. Moreover, the study suggests that the indomethacin-induced liver and renal dysfunction can also be alleviated by the use of trimetazidine.

Review of Clinical Pharmacology and Pharmacokinetics - International EditionVol. 38(3)
Openalex Percentile: Top 83%
Antibiotics Pharmacokinetics and Efficacy
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