Trichopus zeylanicus ameliorates ibuprofen inebriated hepatotoxicity and enteropathy: an insight into its modulatory impact on pro/anti-inflammatory cytokines and apoptotic signaling pathways

Inflammopharmacology. 2022 Dec;30(6):2229-2242. doi: 10.1007/s10787-022-01052-5. Epub 2022 Aug 25.

Abstract

Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used for its analgesic, antipyretic and anti-inflammatory effects worldwide. However ibuprofen comes with serious unavoidable adverse effects on various organs when used for long duration or overdosed. Trichopus zeylanicus is a medicinal plant endemic to India owning various beneficial properties and is been used in treating various ailments. Therefore, the objective of this study was to evaluate the ameliorative effect of aqueous leaves' extract of Trichopus zeylanicus against ibuprofen-induced hepatic toxicity and enteropathy in rats. Overall in this study 30 male albino rats were used, which were divided into five groups (six in each group). Group-I was normal control, Group-II was ibuprofen (400 mg/kg/day) inebriated group, Group-III was silymarin (25 mg/kg/day) pretreated + ibuprofen (400 mg/kg/day), Group-IV was ALETZ (1000 mg/kg/day) pretreated + ibuprofen (400 mg/kg/day), and Group-V was ALETZ alone (1000 mg/kg/day) group. The duration of the administration was for five days, followed by scarifying rats on the sixth day. Later the rats were assessed for liver and intestine enzyme markers, antioxidant parameters along with histopathological changes. In addition the pro-inflammatory markers such as TNF-α, IL-6 and IL-1β as well as anti-inflammatory cytokine IL-10 levels were measured using ELISA. Lastly the expression pattern of apoptotic signaling markers such as caspase-3, caspase-8 and Bcl-2 was evaluated using western blot. The results obtained from this study showed changes in levels of aforesaid parameter which presented the toxic effect of ibuprofen on liver and small intestine. Pre-treatment of ALETZ in ibuprofen-inebriated group was able to normalize the adverse effect caused due to ibuprofen. The conclusion of the study deduces that pre-treatment with ALETZ alleviates by modulating oxidative stress, inflammation, and apoptosis in ibuprofen inebriated rats, indicating its protective mechanism.

Keywords: BCL-2; Caspase-3; Caspase-8; Ibuprofen; Nonsteroidal anti-inflammatory drugs; Trichopus zeylanicus.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antioxidants / pharmacology
  • Apoptosis
  • Chemical and Drug Induced Liver Injury* / drug therapy
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Cytokines* / metabolism
  • Ibuprofen / pharmacology
  • Liver / metabolism
  • Oxidative Stress
  • Rats
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Cytokines
  • Ibuprofen