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Therapeutic potential of rosmarinic acid in tramadol-induced hepatorenal toxicity: Modulation of oxidative stress, inflammation, RAGE/NLRP3, ER stress, apoptosis, and tissue functions parameters.
- Source :
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Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2025 Mar; Vol. 197, pp. 115275. Date of Electronic Publication: 2025 Jan 21. - Publication Year :
- 2025
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Abstract
- Aim: Tramadol (TRM), a widely used opioid analgesic for moderate to severe pain, is associated with liver and kidney toxicity at high doses or prolonged use. This study investigates the protective role of rosmarinic acid (RA), a natural phenolic compound known for its antioxidant, anti-inflammatory, and cell-protective properties, against TRM-induced hepatorenal toxicity.<br />Methods: Thirty-five male Wistar rats were divided into five groups: Control, TRM, RA, TRM + RA25, and TRM + RA50. Rats received TRM (50 mg/kg) and RA (25 or 50 mg/kg), with liver and kidney function tests, oxidative stress, inflammation, ER stress, apoptosis, and tissue damage indicators assessed through qRT-PCR, ELISA, Western blotting, H&E, and immunohistochemical analysis.<br />Results: TRM induced liver and kidney dysfunctions, evident from increased ALT, AST, ALP, urea, creatinine, nephrin, TIM-1 and 8-OHdG levels, along with activated oxidative stress, inflammation, ER stress, and apoptosis pathways. RA significantly reduced these effects, ameliorating histologic and immunohistochemical markers of tissue damage and inflammation.<br />Conclusion: RA demonstrates therapeutic potential by mitigating TRM-induced hepatorenal toxicity and preserving tissue integrity.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2025 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Male
Rats
Chemical and Drug Induced Liver Injury drug therapy
Chemical and Drug Induced Liver Injury metabolism
Inflammation drug therapy
Inflammation chemically induced
Inflammation metabolism
Liver drug effects
Liver metabolism
Rats, Wistar
Receptor for Advanced Glycation End Products metabolism
Apoptosis drug effects
Cinnamates pharmacology
Depsides pharmacology
Endoplasmic Reticulum Stress drug effects
Kidney drug effects
Kidney metabolism
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Oxidative Stress drug effects
Rosmarinic Acid pharmacology
Tramadol toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6351
- Volume :
- 197
- Database :
- MEDLINE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Publication Type :
- Academic Journal
- Accession number :
- 39848458
- Full Text :
- https://doi.org/10.1016/j.fct.2025.115275