Therapeutic potential of rosmarinic acid in tramadol-induced hepatorenal toxicity: Modulation of oxidative stress, inflammation, RAGE/NLRP3, ER stress, apoptosis, and tissue functions parameters

Karaca O., Akaras N., Şimşek H., GÜR C., İLERİTÜRK M., KÜÇÜKLER S., ...Daha Fazla

Food and Chemical Toxicology, cilt.197, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 197
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.fct.2025.115275
  • Dergi Adı: Food and Chemical Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Environment Index, Food Science & Technology Abstracts, Pollution Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: Apoptosis, Hepatorenal, Oxidative stress, Rosmarinic acid, Toxicity, Tramadol
  • Atatürk Üniversitesi Adresli: Evet

Özet

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. 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. 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. Conclusion: RA demonstrates therapeutic potential by mitigating TRM-induced hepatorenal toxicity and preserving tissue integrity.