# Protective Effects of Pentoxifylline on Peripheral Microcirculatory Dysfunction and Renal Cortical Oxygen Deficiency in a Rat Model of LPS‐Induced Sepsis

**Authors:** Bülent Ergin, H. Rob Taal, Deniz Erol Kutucu, Wijnie van Dam, Aysegul Kapucu, Sinno S. H. P. Simons, Can Ince, Irwin K. M. Reiss

PMC · DOI: 10.1111/micc.70056 · Microcirculation (New York, N.y. : 1994) · 2026-03-09

## TL;DR

This study shows that pentoxifylline helps improve blood flow and kidney oxygen levels in rats with sepsis.

## Contribution

The study demonstrates PTX's protective effects on microcirculation and kidney oxygenation in sepsis for the first time.

## Key findings

- PTX improved renal cortical oxygen pressure compared to the LPS group.
- PTX and RA restored perfused vessels and red blood cell velocity in muscle microcirculation.
- Combined PTX and RA reduced renal damage and inflammation more than RA alone.

## Abstract

Sepsis is associated with hypotension, tissue hypoperfusion, and microcirculatory dysfunction leading to multi‐organ failure and mortality. Pentoxifylline (PTX), a phosphodiesterase inhibitor, is reported to improve blood flow and viscosity. The aim of this study was to investigate the efficacy of PTX on peripheral and renal microcirculatory alterations in sepsis.

Fully instrumented Wistar albino rats were randomized as the control group (only surgery), only lipopolysaccharide (LPS) group without treatment (T1), LPS group with PTX treatment (LPS + PTX), LPS group treated with only fluid resuscitation (Ringer's acetate; RA), LPS + RA, LPS group with combined treatment with PTX and RA (LPS + PTX + RA) for 3 h (T2, T3 and T4). The systemic hemodynamics, renal oxygenation, leg muscle microcirculation, histological damage, and inflammatory and endothelial injury markers were analyzed.

The renal cortical microvascular oxygen pressure (cμPO2) was improved by the PTX, RA, and PTX + RA treatments compared to the LPS group (p < 0.05). The proportions of perfused vessels (PPV) and red blood cell velocity (RBCv) were significantly restored by PTX and RA compared with the LPS group at T4 (p < 0.05). Renal damage and inflammatory cell infiltration were reduced by PTX and RA together compared with RA alone (p < 0.05).

In this study, we found that PTX may protect renal oxygenation, peripheral (muscle) microcirculation, renal damage, and tissue inflammatory cell infiltration in a rat model of LPS‐induced sepsis.

## Linked entities

- **Chemicals:** Pentoxifylline (PubChem CID 4740)

## Full-text entities

- **Genes:** Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Lcn2 (lipocalin 2) [NCBI Gene 170496] {aka Sip24}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, Crp (C-reactive protein) [NCBI Gene 25419] {aka Aa1249, Ab1-341, Ab2-196, Ac1-114, Ac1262, Ac2-069}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, HAVCR1 (hepatitis A virus cellular receptor 1) [NCBI Gene 26762] {aka CD365, HAVCR, HAVCR-1, KIM-1, KIM1, TIM}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}
- **Diseases:** renal ischemia (MESH:D007511), hypotension (MESH:D007022), Renal (MESH:D006030), endotoxic (MESH:D012772), infection (MESH:D007239), dilated cardiomyopathy (MESH:D002311), septic (MESH:D001170), tubular damage (MESH:D000230), endothelial injury (MESH:D057772), E. coli  sepsis (MESH:D004927), intra-abdominal sepsis (MESH:D000082122), intermittent claudication (MESH:D007383), renal medullary damage (MESH:C536137), Sepsis (MESH:D018805), hemorrhagic shock (MESH:D012771), Cortical Oxygen Deficiency (MESH:D000860), traumatic (MESH:D014947), Inflammation (MESH:D007249), neonatal sepsis (MESH:D000071074), platelet aggregation (MESH:D001791), multi-organ failure (MESH:D009102), Renal Damage (MESH:D007674), necrotizing enterocolitis (MESH:D020345), thrombus (MESH:D013927), Endotoxemia (MESH:D019446), non-alcoholic steatohepatitis (MESH:D005235), pain (MESH:D010146), death (MESH:D003643), FCD (OMIM:163000), cortical damage (MESH:D054220), RBF (MESH:D054318)
- **Chemicals:** eosin (MESH:D004801), lactate (MESH:D019344), xylene (MESH:D014992), Acetate (MESH:D000085), dexmedetomidine (MESH:D020927), ethanol (MESH:D000431), formalin (MESH:D005557), nitric oxide (MESH:D009569), CaO2 (MESH:C403632), PO2 (MESH:C093415), pd-porphyrin (MESH:C079625), hyaluronan (MESH:D006820), cAMP (MESH:D000242), O2.min (-), RA (MESH:D011883), cGMP (MESH:D006152), paraffin (MESH:D010232), water (MESH:D014867), carbon dioxide (MESH:D002245), Ketamine (MESH:D007649), NaCl (MESH:D012965), LPS (MESH:D008070), PTX (MESH:D010431), glycogen (MESH:D006003), atropine-sulfate (MESH:D001285), O2 (MESH:D010100), hematoxylin (MESH:D006416)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Canis lupus familiaris (dog, subspecies) [taxon 9615], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12971620/full.md

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Source: https://tomesphere.com/paper/PMC12971620