The comparative efficacy of tyloxapol versus pentoxifylline against induced acute phase response in an ovine experimental endotoxemia model

Abstract

The effective treatments of endotoxemia are necessary to prevent high mortality rates. Hence, the present study was performed to clarify the antiendotoxic effects of tyloxapol and pentoxifylline in experimentally induced endotoxemia in sheep. Thirty clinically healthy 1-year-old Iranian fat-tailed ewes were randomly divided into six equal experimental (n = 5) groups, comprising Negative and Positive control, Tyloxapol 1, Tyloxapol 2, Pentoxifylline 1 and Pentoxifylline 2. Phenol extracted lipopolysaccharide from Escherichia coli serotype O55:B5 was infused at 2 µg/kg intravenously. Tyloxapol (200 and 400 mg/kg) and pentoxifylline (30 and 60 mg/kg) were injected to Tyloxapol and Pentoxifylline groups, respectively, at 90 min after endotoxemia induction over 60 min along with intravenous fluids. Blood samples were collected from all ewes prior and 1.5, 3, 4.5, 6, 24 and 48 h after lipopolysaccharide injection and sera and plasmas were separated, subsequently. Haptoglobin, serum amyloid A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), superoxide dismutase and glutathione peroxidase were measured in all samples. Serum concentrations of haptoglobin, serum amyloid A, TNF-α and IFN-γ in Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups were significantly lower than Positive control one after hour 3. There were no significant differences among Tyloxapol and Pentoxifylline groups (P > 0.05). Superoxide dismutase and glutathione peroxidase activities in Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups were significantly lower than Positive control one after hour 3. There were no significant differences among Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups (P > 0.05). Tyloxapol and pentoxifylline act as the anti-inflammatory mediators by decreasing pro-inflammatory cytokines and hepatic APPs and modulating oxidative enzymes activity after endotoxemia induction in sheep. Furthermore, their efficacies at different doses were significantly similar together and both drugs don't induce their effects by dose dependent manner and the anti- and pro-inflammatory effects of them were statistically similar.

Dietary chia seeds (Salvia hispanica) improve acute dyslipidemia and steatohepatitis in rats

“…This finding suggests partial interference from the concomitant administration of TI with the TC‐induced liver damage. TI exerts antioxidant effects as a free radical scavenger and antioxidant enzyme inducer, as well as immunomodulatory/anti‐inflammatory effects by inhibiting the NF‐κB pathway followed by TNF‐α (Chalmeh et al, ; Ghio et al, ; Kuo, Lin, & Tseng, ; Sachs, Ghio, & Young, ). In addition, TI‐induced dyslipidemia lasts up to 72 hr, which suggests that TI is still bioavailable to blunt the TC‐induced injury, as corroborated by histology wherein the liver parenchyma was not as damaged as expected (Rasouli et al, ).…”

A Neonatal Murine Escherichia coli Sepsis Model Demonstrates That Adjunctive Pentoxifylline Enhances the Ratio of Anti- vs. Pro-inflammatory Cytokines in Blood and Organ Tissues

“…Combined PTX and indomethacin treatment of neonatal piglets with group B streptococcal sepsis led to significant reduction of TNF serum levels (44). Other studies have demonstrated that PTX also reduced bacterial endotoxin-induced TNF, interferon γ, and other acute phase reactants in young sheep (45), reversed cerebral ischemiareperfusion-induced TNF and IL-6 levels in adult rats (46), FIGURE 9 | Addition of PTX to GENT profoundly inhibited E. coli-induced plasma TNF and enhanced plasma IL-10 in septic newborn mice. Neonatal mice < 24 h old were injected IV with E. coli 10 5 CFU/g body weight, followed by simultaneous (0 h, n = 7-9), early (1.5 h, n = 18-33), or late (4 h, n = 15-18) IP injection of SAL, GENT, PTX, or GENT + PTX (G + P).…”

“…Combined PTX and indomethacin treatment of neonatal piglets with group B streptococcal sepsis led to significant reduction of TNF serum levels ( 44 ). Other studies have demonstrated that PTX also reduced bacterial endotoxin-induced TNF, interferon γ, and other acute phase reactants in young sheep ( 45 ), reversed cerebral ischemia-reperfusion-induced TNF and IL-6 levels in adult rats ( 46 ), and protected against LPS-induced white matter injury in the developing rat brain ( 47 ), suggesting that PTX can inhibit microbial-induced as well as sterile inflammation.…”

Plasma disposition of florfenicol after intramuscular administration in rabbits pretreated with pentoxifylline

“…Thus, rabbits of Group 2 were premedicated with an oral dose of PTX. The dose selection of PTX was based on experimental data described in sheep by Chalmeh et al (2016). On the other hand, the time of PTX premedication of 45 min was established considering values of Tmax of 47.5 min described in dogs treated with a formulation of PTX in tablets (Marsella et al, 2000).…”