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Short summary of the research and contribution to the field

This preprint evaluates whether rosuvastatin can reduce lung injury in a rat model of cecal ligation and puncture-induced sepsis. The authors tested two rosuvastatin doses, 10 mg/kg and 20 mg/kg, and assessed oxidative stress markers, histopathological lung injury, and immunohistochemical markers related to inflammation, apoptosis, and DNA damage.

The study addresses an important question because sepsis-associated acute lung injury is driven by oxidative stress, inflammation, apoptosis, and tissue damage. The findings suggest that rosuvastatin reduced MDA levels, restored GSH levels, improved lung histopathology, and lowered NF-κB/p65, caspase-3, and 8-OHdG expression. These results support a potential protective effect of rosuvastatin in experimental sepsis-induced lung injury.

Positive feedback / strengths

1. Clinically relevant topic. Sepsis-associated acute lung injury remains a major clinical problem, and exploring anti-inflammatory and antioxidant approaches is valuable.

2. Appropriate animal model. The cecal ligation and puncture model is a commonly used experimental model for polymicrobial sepsis and is relevant for studying systemic inflammation and organ injury.

3. Multiple injury pathways assessed. The study evaluates oxidative stress, inflammation, apoptosis, DNA damage, and histopathology, which provides a broader picture of lung injury than a single endpoint.

4. Dose comparison included. Testing both 10 mg/kg and 20 mg/kg rosuvastatin adds useful information, especially since no clear difference was observed between doses.

5. Histological and molecular evidence are combined. The combination of biochemical markers, tissue morphology, and immunohistochemistry strengthens the biological interpretation.

Major issues

1. The study should clarify whether rosuvastatin is preventive or therapeutic

Rosuvastatin was given before the CLP procedure, which makes the study primarily a pretreatment/prevention model, not a treatment model after sepsis has already developed.

Suggested improvement: The authors should clearly state that the results support prophylactic or preconditioning effects. To support therapeutic relevance, an additional group receiving rosuvastatin after CLP would be helpful.

2. Lack of dose-response effect needs careful interpretation

The abstract states that there were no significant differences between the two rosuvastatin doses. This is important because it may suggest a ceiling effect, insufficient dose separation, or limited statistical power.

Suggested improvement: The authors should discuss why 10 mg/kg and 20 mg/kg produced similar effects and avoid implying that higher dosing provides additional benefit unless supported by data.

3. Clinical translation should be framed cautiously

Although the experimental results are promising, the model used short-term pretreatment and a 16-hour endpoint. This does not fully reflect clinical sepsis management, where treatment usually begins after diagnosis.

Suggested improvement: The conclusion should be softened. Instead of suggesting direct therapeutic potential, the authors could state that rosuvastatin shows protective effects in an experimental model and warrants further mechanistic and post-treatment studies.

4. More detail is needed on randomization, blinding, and sample size

For animal studies, interpretation depends heavily on proper randomization, blinded histopathology scoring, blinded immunohistochemistry quantification, and adequate sample size.

Suggested improvement: The manuscript should clearly report animal numbers per group, sex distribution, randomization method, blinding procedures, exclusion criteria, and power/sample-size justification.

5. Histopathology and immunohistochemistry should be quantitatively described

The abstract reports improvement in inflammation, vascular congestion, septal thickness, and marker expression, but the strength of these conclusions depends on scoring methods.

Suggested improvement: The authors should explain the scoring system, number of fields analyzed, magnification, reviewer blinding, image quantification method, and statistical handling of histology/IHC data.

6. Additional systemic sepsis markers would strengthen the study

The study focuses on lung tissue markers, but sepsis severity is systemic.

Suggested improvement: If available, the authors should include or discuss systemic indicators such as survival, clinical severity score, serum cytokines, lactate, bacterial burden, arterial oxygenation, WBC count, or extrapulmonary organ injury markers.

Minor issues

1. Clarify the wording: “administered via oral gavage before 4 hours the CLP procedure” should be revised to “4 hours before the CLP procedure.”

2. Define all abbreviations at first use, including CLP, ALI, MDA, GSH, NF-κB, and 8-OHdG.

3. Clarify whether rosuvastatin was administered once or repeatedly.

4. Report whether sham + rosuvastatin groups showed any independent lung or biochemical effects.

5. Include representative histology and IHC images with scale bars.

6. Clarify the statistical tests used for multiple group comparisons.

7. Avoid overstatement if the results are based only on short-term experimental endpoints.

Overall assessment

This is a well-motivated experimental study addressing an important question in sepsis-induced acute lung injury. The main strengths are the use of a CLP sepsis model, assessment of multiple injury pathways, inclusion of two rosuvastatin doses, and combined biochemical, histological, and immunohistochemical analyses.

The most important improvements would be clearer framing of rosuvastatin as a pretreatment rather than a post-sepsis therapy, more detail on randomization/blinding/sample size, quantitative reporting of histology and IHC scoring, and cautious interpretation of clinical applicability. With these revisions, the manuscript would provide a stronger and more balanced contribution to the experimental sepsis and lung injury literature.

Competing interests

The author declares that they have no competing interests.

Use of Artificial Intelligence (AI)

The author declares that they used generative AI to come up with new ideas for their review.