The Effect of Advanced Glycation End-Products and Aminoguanidine on Tnfα Production by Rat Peritoneal Macrophages

Abstract

Objective To evaluate the effect of advanced glycation end-products (AGEs) and the inhibitor of their formation, aminoguanidine, on tumor necrosis factor-α (TNFα) production (as a functional marker) by rat peritoneal macrophages (PMΦ). Design Charles River rats underwent a daily intraperitoneal injection of peritoneal dialysis solution [(PDS), 4.25 g/dL dextrose; Dialine, Travenol, Ashdod, Israel] for a 2-month period (group E). Another group of rats was subjected to the same protocol with the addition of 25 mg/kg aminoguanidine (group A). Three control groups were utilized: ( 1 ) rats that were injected daily with aminoguanidine only (group AO), ( 2 ) rats that were injected with Dulbecco's phosphate-buffered saline (group D), and ( 3 ) rats in which no intervention was carried out (group C). After 2 months, PMΦ were isolated from rat peritoneal effluent and their TNFα production measured by ELISA in cell-free culture supernatants, in both the basal state and after 24-hour stimulation with lipopolysaccharide (LPS). The concentrations of AGEs in peritoneal effluent were assayed and correlated to TNFα levels. PMΦ obtained from normal rats were then incubated for 24 hours with ( 1 ) the peritoneal effluent of each of the above respective groups, with or without LPS; ( 2 ) increasing concentrations of AGEs (0 - 250 μg/mL); and ( 3 ) increasing concentrations of aminoguanidine (0 - 7.5 mg/mL), and TNFα secretion again determined. Results After 2 months of daily intraperitoneal injection of PDS, in the basal state, TNFα production was significantly higher in PMΦ isolated from the peritoneal effluent groups (groups E, A, and AO) compared to controls (group C). Following LPS stimulation, a further increase in TNFα secretion was seen, with a significantly greater response in group AO versus groups E, A, and D. Effluent AGEs were markedly elevated only in group E. No correlation was found between TNFα secretion by these PMΦ and the concentration of AGEs. On incubation with the respective peritoneal effluents (groups E, A, and AO), in both the basal and stimulated state, TNFα production by PMΦ from normal rats was significantly enhanced compared to group C. Incubation with increasing concentrations of AGEs or aminoguanidine resulted in an increase of TNFα secretion by these PMΦ. Conclusions Following intermittent intraperitoneal administration of glucose-based PDS, rat PMΦ are chronically activated, as evidenced by increased basal TNFα secretion. The peritoneal effluent of such treated animals is capable of stimulating TNFα production by normal rat PMΦ. These data suggest that glucose-based PDS acts as a primer of PMΦ, which retain their ability to further stimulation by LPS. Although, in vitro, AGEs promote TNFα secretion by normal rat PMΦ, in vivo, their influence is probably modulated by other factors. Aminoguanidine has a specific inducing effect on rat PMΦ, independent of glucose-based PDS.

In vitro effect of advanced glycation end‐products on human polymorphonuclear superoxide production

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Histopathological Changes at Colonic Anastomotic Site after Ischemia Reperfusion Injury: Role of Aminoguanidine in Experimental Model

“…They injected peritoneal dialysis solution and AG for 2 months in different groups of rats and concluded beneficial role of AG on rat peritoneum. 29 Ara et al also studied protective effect of AG against oxidative stress in an experimental peritoneal adhesion model in rats and concluded that intraperitoneal administration of AG decreases the incidence and extent of peritoneal adhesions and causes a decrease in malondialdehyde, total nitrite/nitrate, and reduced glutathione. 30 But use of NOS inhibitors is not without its hazards.…”

Effects of fermented red bean extract on nephropathy in streptozocin-induced diabetic rats

“…Each 100 mL elute was collected, concentrated, and freeze-dried for further assay of antioxidant activities, α-iphenyl-β-picryl-hydrazyl (DPPH) scavenge, and lipid peroxidation inhibition. Fractions of 7,8,23,39,40,42,43,44,45, and 46, which showed high activity either on DPPH scavenge or lipid peroxidation inhibition, were combined and recrystallized, and then identified by 13C NMR.…”

“…TNF-α activation may induce apoptosis of renal cells, abnormal blood flow, and tubulointerstitial fibrosis, which result in glomerular damage (37). ROS promotes the production of TNF-α in renal mesangial cells, and AGEs also stimulate NO, ROS, TNFα, and IL-1 secretion from macrophages, which cause inflammation and subsequent renal damage (5,(38)(39)(40).…”