In vivo effects of pentoxifylline on enzyme and non‐enzyme antioxidant levels in rat liver after carrageenan‐induced paw inflammation

Abstract

The present study aimed to investigate the effects of pentoxifylline (PTX) on the carrageenan (CG)-induced paw oedema and on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver, 4 and 24 h after CG injection. PTX (50 mg kg(-1) , i.p.), administered 30 min before CG, decreased the paw oedema, 2-4 h after CG administration. The drug protected CG-induced decrease of glutathione (non-enzyme antioxidant) and had no effect on CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of GSH-conjugated antioxidant enzymes). The drug showed a good antioxidant capacity in chemical systems, generating reactive oxygen species. The present results suggest that the antioxidant activity of PTX might contribute to its beneficial effects in liver injuries.

Edematogenic activity of a sulfated galactan from the red marine algaeGelidium crinale

“…The same results were reported by Stochla and Maslinski (1982), pointing that SG-Gc, but not carrageenan induces histamine release, via mast cell activation, that precedes activation of histamine receptors. Moreover, the involvement of late phase mediators in the two types of edema were shown to be differentiated, according to several evidences using classical protocols of pharmacological blockage: (1) indomethacin, nonspecific inhibitor of the enzyme (cyclooxygenase) responsible for prostaglandins production (Kankuri et al, 2001), inhibited the edematogenic effect of SG-Gc by 69% ( Figure 2D) and that of carrageenan by 44% (Garcia Leme et al, 1973); (2) l-NAME, nonspecific inhibitor of the enzyme NOS responsible for NO production (Moncada et al, 1991), inhibited the edematogenic effect of SG-Gc by 72% ( Figure 2D) and that of carrageenan by 25% (Salvemini et al, 1996); (3) pentoxifylline, inhibitor of the enzyme phosphodiesterase responsible for synthesis of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and IL-1 inhibited the edematogenic effect of SG-Gc by 49% ( Figure 2D) and that of carrageenan by 40% (Vircheva et al, 2010).…”

“…treatment with compound 48/80 (0.6 mg/kg on Days 1-3 and 1.2 mg/kg on Day 4), a mast cell degranulator (Ohta et al, 2003). For the involvement of late-phase mediators, indomethacin (5 mg/kg; s.c.), inhibitor of the enzyme cyclooxygenase (Kankuri et al, 2001), pentoxifylline (90 mg/kg; s.c.), inhibitor of the enzyme phosphodiesterase (Vircheva et al, 2010) or NG-nitro-l-arginine methyl ester (l-NAME) (25 mg/kg; i.v. ), inhibitor of the enzyme NOS (Moncada et al, 1991), were administered 1 h before edema induction with SG-Gc.…”

Pentoxifylline decreases soluble CD40 ligand concentration and CD40 gene expression in coronary artery disease patients

“…Furthermore, it was shown that compounds with antioxidant activity down-regulate CD40/CD40L system. (23) Since the pentoxifylline also showed the antioxidant activity in rats with liver injuries, (30) it seems that the mechanism was also involved in the inhibitory effect of pentoxifylline on activation of CD40/CD40L system.…”

Reversal of liver fibrosis: From fiction to reality

“…In addition to encouraging data showing the potential efficacy of serelaxin for renal dysfunction in liver cirrhosis (127), there is currently a phase II clinical trial assessing the efficacy of serelaxin in cirrhotic patients with portal hypertension (NCT02669875). is a methylxanthine derivative that suppresses production of TNF-α and other proinflammatory cytokines as well as decreases oxidative stress (132). In NASH patients, pentoxifylline treatment improved the extent of liver fibrosis (133), whereas no obvious effect was seen in patients with severe alcoholic hepatitis (134).…”