Ebrahem, N., Makboul, R., Elkabsh, M., Shaltout, E., Abdellah, N. (2022). Sub chronic Toxicity of Pregabalin and Possible Fibrotic Changes in Ovaries, Kidneys, Heart, and Lungs of Female Rats. Zagazig Journal of Forensic Medicine and Toxicology, 20(1), 175-189. doi: 10.21608/zjfm.2022.95220.1091
Noha Esmael Ebrahem; Rania M.A. Makboul; Mai M Elkabsh; Eman S Shaltout; Nora Zedan Abdellah. "Sub chronic Toxicity of Pregabalin and Possible Fibrotic Changes in Ovaries, Kidneys, Heart, and Lungs of Female Rats". Zagazig Journal of Forensic Medicine and Toxicology, 20, 1, 2022, 175-189. doi: 10.21608/zjfm.2022.95220.1091
Ebrahem, N., Makboul, R., Elkabsh, M., Shaltout, E., Abdellah, N. (2022). 'Sub chronic Toxicity of Pregabalin and Possible Fibrotic Changes in Ovaries, Kidneys, Heart, and Lungs of Female Rats', Zagazig Journal of Forensic Medicine and Toxicology, 20(1), pp. 175-189. doi: 10.21608/zjfm.2022.95220.1091
Ebrahem, N., Makboul, R., Elkabsh, M., Shaltout, E., Abdellah, N. Sub chronic Toxicity of Pregabalin and Possible Fibrotic Changes in Ovaries, Kidneys, Heart, and Lungs of Female Rats. Zagazig Journal of Forensic Medicine and Toxicology, 2022; 20(1): 175-189. doi: 10.21608/zjfm.2022.95220.1091
Sub chronic Toxicity of Pregabalin and Possible Fibrotic Changes in Ovaries, Kidneys, Heart, and Lungs of Female Rats
1forensic medicine and clinical toxicology , faculty of medicine, assiut univewrsity
2Assistant Professor of Pathology, Pathology Department, Faculty of Medicine, Assiut University, Egypt
3Department of Pathology, Faculty of Medicine-Assiut University-Egyp
4Lecturer of Forensic Medicine and Clinical Toxicology, Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Assiut University, Egypt
5Assistant Professor of Forensic Medicine and Clinical Toxicology, Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Assiut University, Egypt
Abstract
Background: Pregabalin is an anti-epileptic drug that was approved as neuropathic pain therapy. Incidence of adverse Background: Pregabalin is an anti-epileptic drug that was approved as neuropathic pain therapy. Incidence of adverse reactions with pregabalin were reported to be related to dosage. Aim: This is a sub-chronic study to assess the possible fibrotic changes in lung, heart, kidney, and ovary as a result of long-term exposure to pregabalin. Material and Methods: Thirty female rats were divided equally into 3 groups (I, II and III). Group I (negative control group): received nothing. Group II (positive control): received 0.5 ml saline via gastric gavage daily for 8 weeks. 600 mg/kg body weight/day (a dose equivalent to 6 times the therapeutic dose and 1/10th the maximum non-lethal dose) of Pregabalin was given to group III for 8 weeks. At the end of the study, rats were sacrificed. Kidney, lung heart and ovary specimens were taken for histopathological examination using Hematoxylin-eosin and Masson trichrome stain to demonstrate fibrosis. Results: The body weight of rats showed non significant difference between the 3 groups. Also weights of ovaries, kidneys, hearts, and lungs the 3 groups showed non significant difference. Ovariantissue of female rats treated with pregabalin showed decreased number of follicles and increased stromal fibrosis. Interstitial fibrosis of kidney sections was also demonstrated. Heart sections of treated rats showed fibrosis between muscle fibers. Also, lung section showed patchy areas of dense fibrosis and inflammation. Conclusion: The present study demonstrated ovarian, renal, pulmonary, and myocardial fibrosis in female rats after 8 weeks of daily oral administration of pregabalin. This raises a concern about the potential ability of pregabalin to induce fibrosis and the relationship between pregabalin induced fibrosis and organ failure. Recommendations: Clinicians should assess the benefit-risk balance in patients before prescribing pregabalin; the patients should be screened for fibrosis before treatment and at regular intervals thereafter.
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