# Relationship Between the Duration of Intravenous Ketamine Anesthesia and Postoperative Oxidative Stress and Inflammatory Response in Rats

**Authors:** Ramazan Ince, Habip Burak Ozgodek, Agah Abdullah Kahramanlar, Nurinisa Yucel, Cengiz Sarıgül, Halis Suleyman

PMC · DOI: 10.3390/ijms26199465 · International Journal of Molecular Sciences · 2025-09-27

## TL;DR

This study shows that longer ketamine anesthesia in rats reduces post-surgery oxidative stress and inflammation.

## Contribution

The study reveals that ketamine's effects on oxidative stress and inflammation depend on the duration of anesthesia.

## Key findings

- Single-dose ketamine increased oxidative stress and inflammation after surgery in rats.
- Repeated ketamine doses reduced oxidative stress markers and restored antioxidant levels toward control values.
- Prolonged ketamine anesthesia improved catecholamine balance and reduced pro-inflammatory cytokines.

## Abstract

Surgical trauma triggers oxidative and inflammatory responses that contribute to postoperative complications. Although the antioxidant and anti-inflammatory effects of ketamine have been reported, the impact of anesthesia duration on these mechanisms remains unclear. Forty-two male Wistar rats were randomized into healthy control (HG), ketamine only (KET; 60 mg/kg, i.p.), or laparotomy plus ketamine with 0–4 additional ketamine doses at 20 min intervals (KET + L, KET + L1–L4). At 24 h, levels of MDA, tGSH, SOD, CAT, IL-1β, IL-6, TNF-α, adrenaline and noradrenaline were measured in tail-vein blood. One-way ANOVA with Tukey’s post hoc test was used. Laparotomy under single-dose ketamine increased MDA and pro-inflammatory cytokines and decreased tGSH, SOD, CAT, ADR, and NDR versus HG and KET (all p < 0.001). After laparotomy, repeated ketamine dosing produced graded decreases in MDA and cytokines and increases in tGSH, SOD, CAT, ADR, and NDR toward control levels; effects were most pronounced in KET + L4 (all p < 0.001). Ketamine alone did not differ significantly from HG. In rats, ketamine modulates postoperative biological stress in a duration-dependent manner; prolonging anesthesia reduces oxidative–inflammatory load and restores catecholaminergic tone. These findings strongly support revisiting dose–duration protocols and underscore the need for mechanistic and clinical studies.

## Linked entities

- **Proteins:** SOD1 (superoxide dismutase 1), CAT (catalase), IL1B (interleukin 1 beta), IL6 (interleukin 6), TNF (tumor necrosis factor)
- **Chemicals:** ketamine (PubChem CID 3821), MDA (PubChem CID 1614), tGSH (PubChem CID 833466), adrenaline (PubChem CID 838), noradrenaline (PubChem CID 951)

## Full-text entities

- **Genes:** Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}
- **Diseases:** trauma (MESH:D014947), Inflammatory (MESH:D007249)
- **Chemicals:** adrenaline (MESH:D004837), Ketamine (MESH:D007649), MDA (MESH:D015104), NDR (-), noradrenaline (MESH:D009638), ADR (MESH:D004317)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12524368/full.md

## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12524368/full.md

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Source: https://tomesphere.com/paper/PMC12524368