Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats
Abstract Background Trihexyphenidyl (THP), an anticholinergic drug used to manage Parkinson’s disease and dystonia, has been associated with oxidative stress and metabolic disturbances, particularly affecting pulmonary function. Long-term exposure to THP may induce lung toxicity through increased ox...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s40360-025-00955-7 |
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| author | Joseph Gbenga Omole Lydia Oluwatoyin Ajayi Itunuoluwa Rachael Ajewole Teniola Osholonge Oyedayo Phillips Akano Ayodeji Folorunsho Ajayi |
| author_facet | Joseph Gbenga Omole Lydia Oluwatoyin Ajayi Itunuoluwa Rachael Ajewole Teniola Osholonge Oyedayo Phillips Akano Ayodeji Folorunsho Ajayi |
| author_sort | Joseph Gbenga Omole |
| collection | DOAJ |
| description | Abstract Background Trihexyphenidyl (THP), an anticholinergic drug used to manage Parkinson’s disease and dystonia, has been associated with oxidative stress and metabolic disturbances, particularly affecting pulmonary function. Long-term exposure to THP may induce lung toxicity through increased oxidative stress, mitochondrial dysfunction, and apoptosis. Coenzyme Q10 (CoQ10), a lipid-soluble antioxidant and mitochondrial cofactor, has been shown to protect against oxidative damage and apoptosis in various models of toxicity. However, its role in mitigating THP-induced pulmonary toxicity remains unexplored. This study investigated the protective effects of CoQ10 against THP-induced pulmonary toxicity in male Wistar rats. Methods Thirty-two adult male Wistar rats (180–200 g) were randomly assigned to four groups (n = 8 per group): (i) Control (vehicle-treated), (ii) THP (1.5 mg/kg), (iii) CoQ10 (10 mg/kg), and (iv) THP + CoQ10. Treatments were administered orally once daily for 21 days. Body weight was recorded at baseline and endpoint. At the end of treatment, rats were euthanized, and lungs were excised, weighed, and processed for biochemical and histological analyses. Oxidative stress markers were assessed, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA). Metabolic enzymes such as lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were measured. Angiotensin-converting enzyme (ACE) activity was evaluated to assess vascular function, while caspase-3 levels were determined as an apoptotic marker. Histopathological examination of lung tissues was performed using hematoxylin and eosin staining. Results THP administration resulted in significant weight loss, increased lung weight, oxidative stress (decreased CAT, GPx, SOD, and GSH; increased MDA), and metabolic alterations (elevated LDH, PDH, lactate, and pyruvate). ACE activity was reduced, and caspase-3 was elevated, indicating apoptosis. CoQ10 co-administration mitigated these effects, restoring antioxidant enzyme activity, metabolic balance, and ACE levels while reducing MDA and caspase-3 expression. Histological analysis confirmed that CoQ10 ameliorated THP-induced pulmonary damage. Conclusion CoQ10 demonstrated significant protective effects against THP-induced oxidative stress, metabolic disturbances, and apoptosis, likely due to its antioxidant and anti-inflammatory properties. These findings suggest CoQ10 as a potential therapeutic agent for THP-induced pulmonary toxicity, warranting further research. Clinical trial number Not applicable. |
| format | Article |
| id | doaj-art-9b02811d5f0d4287a1c861e62aed1cae |
| institution | DOAJ |
| issn | 2050-6511 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Pharmacology and Toxicology |
| spelling | doaj-art-9b02811d5f0d4287a1c861e62aed1cae2025-08-20T03:16:56ZengBMCBMC Pharmacology and Toxicology2050-65112025-05-0126111310.1186/s40360-025-00955-7Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar ratsJoseph Gbenga Omole0Lydia Oluwatoyin Ajayi1Itunuoluwa Rachael Ajewole2Teniola Osholonge3Oyedayo Phillips Akano4Ayodeji Folorunsho Ajayi5Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo UniversityDepartment of Biochemistry, Ladoke Akintola University of TechnologyDepartment of Physiology, Ladoke Akintola University of TechnologyDepartment of Physiology, Ladoke Akintola University of TechnologyDepartment of Physiology, Faculty of Basic Medical Sciences, Olabisi Onabanjo UniversityDepartment of Physiology, Ladoke Akintola University of TechnologyAbstract Background Trihexyphenidyl (THP), an anticholinergic drug used to manage Parkinson’s disease and dystonia, has been associated with oxidative stress and metabolic disturbances, particularly affecting pulmonary function. Long-term exposure to THP may induce lung toxicity through increased oxidative stress, mitochondrial dysfunction, and apoptosis. Coenzyme Q10 (CoQ10), a lipid-soluble antioxidant and mitochondrial cofactor, has been shown to protect against oxidative damage and apoptosis in various models of toxicity. However, its role in mitigating THP-induced pulmonary toxicity remains unexplored. This study investigated the protective effects of CoQ10 against THP-induced pulmonary toxicity in male Wistar rats. Methods Thirty-two adult male Wistar rats (180–200 g) were randomly assigned to four groups (n = 8 per group): (i) Control (vehicle-treated), (ii) THP (1.5 mg/kg), (iii) CoQ10 (10 mg/kg), and (iv) THP + CoQ10. Treatments were administered orally once daily for 21 days. Body weight was recorded at baseline and endpoint. At the end of treatment, rats were euthanized, and lungs were excised, weighed, and processed for biochemical and histological analyses. Oxidative stress markers were assessed, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA). Metabolic enzymes such as lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were measured. Angiotensin-converting enzyme (ACE) activity was evaluated to assess vascular function, while caspase-3 levels were determined as an apoptotic marker. Histopathological examination of lung tissues was performed using hematoxylin and eosin staining. Results THP administration resulted in significant weight loss, increased lung weight, oxidative stress (decreased CAT, GPx, SOD, and GSH; increased MDA), and metabolic alterations (elevated LDH, PDH, lactate, and pyruvate). ACE activity was reduced, and caspase-3 was elevated, indicating apoptosis. CoQ10 co-administration mitigated these effects, restoring antioxidant enzyme activity, metabolic balance, and ACE levels while reducing MDA and caspase-3 expression. Histological analysis confirmed that CoQ10 ameliorated THP-induced pulmonary damage. Conclusion CoQ10 demonstrated significant protective effects against THP-induced oxidative stress, metabolic disturbances, and apoptosis, likely due to its antioxidant and anti-inflammatory properties. These findings suggest CoQ10 as a potential therapeutic agent for THP-induced pulmonary toxicity, warranting further research. Clinical trial number Not applicable.https://doi.org/10.1186/s40360-025-00955-7Coenzyme Q10TrihexyphenidylOxidative stressLung toxicityAntioxidant enzymesLactate dehydrogenase |
| spellingShingle | Joseph Gbenga Omole Lydia Oluwatoyin Ajayi Itunuoluwa Rachael Ajewole Teniola Osholonge Oyedayo Phillips Akano Ayodeji Folorunsho Ajayi Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats BMC Pharmacology and Toxicology Coenzyme Q10 Trihexyphenidyl Oxidative stress Lung toxicity Antioxidant enzymes Lactate dehydrogenase |
| title | Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats |
| title_full | Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats |
| title_fullStr | Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats |
| title_full_unstemmed | Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats |
| title_short | Protective role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats |
| title_sort | protective role of coenzyme q10 against trihexyphenidyl induced pulmonary toxicity in wistar rats |
| topic | Coenzyme Q10 Trihexyphenidyl Oxidative stress Lung toxicity Antioxidant enzymes Lactate dehydrogenase |
| url | https://doi.org/10.1186/s40360-025-00955-7 |
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