Recent progress in adverse events of carboxylic acid non-steroidal anti-inflammatory drugs (CBA-NSAIDs) and their association with the metabolism: the consequences on mitochondrial dysfunction and oxidative stress, and prevention with natural plant extracts

Expert Opin Drug Metab Toxicol. 2024 Aug;20(8):765-785. doi: 10.1080/17425255.2024.2378885. Epub 2024 Jul 12.

Abstract

Introduction: Carboxylic acid non-steroidal anti-inflammatory drugs (CBA-NSAIDs) are extensively used worldwide due to their antipyretic, analgesic, and anti-inflammatory effects. CBA-NSAIDs have reasonable margin of safety at therapeutic doses, and in the current climate, do not possess addiction potential like opioid drugs. Studies have revealed that various adverse events of CBA-NSAIDs are related mitochondrial dysfunction and oxidative stress.

Areas covered: This review article summarizes adverse events induced by CBA-NSAIDs, mechanisms of mitochondrial damage, oxidative stress, and metabolic interactions. Meanwhile, this review discusses the treatment and prevention of CBA-NSAIDs damage by natural plant extracts based on antioxidant effects.

Expert opinion: CBA-NSAIDs can induce reactive oxygen species (ROS) production, mediate DNA, protein and lipid damage, lead to imbalance of cell antioxidant status, change of mitochondrial membrane potential, activate oxidative stress signal pathway, thus leading to oxidative stress and cell damage. Adverse events caused by CBA-NSAIDs often exhibit dose and time dependence. In order to avoid adverse events caused by CBA-NSAIDs, it is necessary to provide detailed patient consultation and eliminate influencing factors. Moreover, constructive research studies on the organ-specific toxicity and mechanism of natural plant extracts in preventing and treating metabolic abnormalities of CBA-NSAIDs, will provide important value for warning and guidance for use of CBA-NSAIDs.

Keywords: Carboxylic acid NSAIDs; adverse events; metabolism; mitochondrial dysfunction; oxidative stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal* / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal* / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Antioxidants* / administration & dosage
  • Antioxidants* / adverse effects
  • Antioxidants* / pharmacology
  • Carboxylic Acids / adverse effects
  • Carboxylic Acids / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Oxidative Stress* / drug effects
  • Plant Extracts* / administration & dosage
  • Plant Extracts* / adverse effects
  • Plant Extracts* / pharmacology
  • Reactive Oxygen Species* / metabolism

Substances

  • Plant Extracts
  • Reactive Oxygen Species
  • Antioxidants
  • Anti-Inflammatory Agents, Non-Steroidal
  • Carboxylic Acids