Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors
Though quinoline anti-infective agents-associated neurotoxicity has been reported in the early 1970s, it only recently received regulatory recognition. In 2019, the European Medicines Agency enforced strict use for quinoline antibiotics. Thus, the current study evaluates the relation between subacut...
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MDPI AG
2022-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/2/251 |
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| author | Ahmed S. Kamel Ahmed F. Mohamed Mostafa A. Rabie Marwa E. Elsherbiny Kawkab A. Ahmed Mahmoud M. Khattab Noha F. Abdelkader |
| author_facet | Ahmed S. Kamel Ahmed F. Mohamed Mostafa A. Rabie Marwa E. Elsherbiny Kawkab A. Ahmed Mahmoud M. Khattab Noha F. Abdelkader |
| author_sort | Ahmed S. Kamel |
| collection | DOAJ |
| description | Though quinoline anti-infective agents-associated neurotoxicity has been reported in the early 1970s, it only recently received regulatory recognition. In 2019, the European Medicines Agency enforced strict use for quinoline antibiotics. Thus, the current study evaluates the relation between subacute exposure to diiodohydroxyquinoline (DHQ), a commonly misused amebicide, with the development of motor and sensory abnormalities, highlighting age and gender as possible predisposing factors. Eighty rats were randomly assigned to eight groups according to their gender, age, and drug exposure; namely, four control groups received saline (adult male, adult female, young male, and young female), and the other four groups received DHQ. Young and adult rats received DHQ in doses of 176.7 and 247.4 mg/kg/day, respectively. After 4 weeks, rats were tested for sensory abnormality using analgesiometer, hot plate, and hind paw cold allodynia tests, and for motor function using open field and rotarod tests. Herein, the complex behavioral data were analyzed by principal component analysis to reduce the high number of variables to a lower number of representative factors that extracted components related to sensory, motor, and anxiety-like behavior. Behavioral outcomes were reflected in a histopathological examination of the cerebral cortex, striatum, spinal cord, and sciatic nerve, which revealed degenerative changes as well demyelination. Noteworthy, young female rats were more susceptible to DHQ’s toxicity than their counterparts. Taken together, these findings confirm previous safety concerns regarding quinoline-associated neurotoxicity and provide an impetus to review risk/benefit balance for their use. |
| first_indexed | 2024-03-09T21:14:34Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T21:14:34Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-01296fe371764e2eab422bc0594599542023-11-23T21:35:27ZengMDPI AGPharmaceuticals1424-82472022-02-0115225110.3390/ph15020251Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing FactorsAhmed S. Kamel0Ahmed F. Mohamed1Mostafa A. Rabie2Marwa E. Elsherbiny3Kawkab A. Ahmed4Mahmoud M. Khattab5Noha F. Abdelkader6Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza 11562, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza 11562, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza 11562, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, 6th of October City 12566, EgyptDepartment of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza 11562, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza 11562, EgyptThough quinoline anti-infective agents-associated neurotoxicity has been reported in the early 1970s, it only recently received regulatory recognition. In 2019, the European Medicines Agency enforced strict use for quinoline antibiotics. Thus, the current study evaluates the relation between subacute exposure to diiodohydroxyquinoline (DHQ), a commonly misused amebicide, with the development of motor and sensory abnormalities, highlighting age and gender as possible predisposing factors. Eighty rats were randomly assigned to eight groups according to their gender, age, and drug exposure; namely, four control groups received saline (adult male, adult female, young male, and young female), and the other four groups received DHQ. Young and adult rats received DHQ in doses of 176.7 and 247.4 mg/kg/day, respectively. After 4 weeks, rats were tested for sensory abnormality using analgesiometer, hot plate, and hind paw cold allodynia tests, and for motor function using open field and rotarod tests. Herein, the complex behavioral data were analyzed by principal component analysis to reduce the high number of variables to a lower number of representative factors that extracted components related to sensory, motor, and anxiety-like behavior. Behavioral outcomes were reflected in a histopathological examination of the cerebral cortex, striatum, spinal cord, and sciatic nerve, which revealed degenerative changes as well demyelination. Noteworthy, young female rats were more susceptible to DHQ’s toxicity than their counterparts. Taken together, these findings confirm previous safety concerns regarding quinoline-associated neurotoxicity and provide an impetus to review risk/benefit balance for their use.https://www.mdpi.com/1424-8247/15/2/251diiodohydroxyquinolineneurotoxicityold/young/male/female ratsbehavioral impairmenthistopathological abnormalitiesprincipal component analysis |
| spellingShingle | Ahmed S. Kamel Ahmed F. Mohamed Mostafa A. Rabie Marwa E. Elsherbiny Kawkab A. Ahmed Mahmoud M. Khattab Noha F. Abdelkader Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors Pharmaceuticals diiodohydroxyquinoline neurotoxicity old/young/male/female rats behavioral impairment histopathological abnormalities principal component analysis |
| title | Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors |
| title_full | Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors |
| title_fullStr | Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors |
| title_full_unstemmed | Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors |
| title_short | Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors |
| title_sort | experimental evidence for diiodohydroxyquinoline induced neurotoxicity characterization of age and gender as predisposing factors |
| topic | diiodohydroxyquinoline neurotoxicity old/young/male/female rats behavioral impairment histopathological abnormalities principal component analysis |
| url | https://www.mdpi.com/1424-8247/15/2/251 |
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