Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Abstract

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-b were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-b in dialysate may be one of the possible underlying mechanisms.

TRPA1 Mechanoreceptors Mediate the IL-6 Response to a Single PD Dwell in the Rat

“…There is clinical and experimental evidence that persistent intraperitoneal inflammation may predispose the membrane to progressive fibrosis (22). However, concerning the connection between fibrosis and IL-6 secretion following pharmacological intervention, some studies show a negative correlation (31) and others show a positive correlation (32). In an experimental model of repeated acute peritoneal inflammation in mice, there was, however, a causal connection between IL-6 production and the development of peritoneal fibrosis (33).…”

Simvastatin-Loaded Nanocapsules Reduce TNF-Α Expression in Rat Peritoneum After Infusion of Peritoneal Dialysis Solution

“…Besides that, a previous animal study involving the administration of SV at 25 mg/kg did not observe changes in bone tissue, after ovariectomy, or in bone healing of rats [33]. However, the use of atorvastatin added into drinking water at a dose of 80 mg/mL provided significant minor fibrosis and thinner peritoneum [15]. In general, Wistar rats usually drink 20-50 mL water a day (10 mL/100 g body weight/day) [34].…”

“…The main findings were greater inflammation, fibrosis, and vascular proliferation in the PD group than in the Sham group. These features seemed to decrease significantly when atorvastatin was used as TX [15].…”

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“…In the future, with a prolonged course of CE, the immunological changes occurring in the endometrium (pathological lymphohistioplasmocytic infiltration of the stroma, changes in the phenotypic composition of cells and the ratio of Th1-and Th2-type cytokines) themselves begin to act as an etiological factor in the violation of implantation processes and the development of chorion, with subsequent formation of women infertility autoimmune genesis [18,19]. In this regard, in-depth data in the study of immune changes will make it possible to develop new methods for the diagnosis and treatment of this pathology, and reduce the level of chronicity of the process, and the economic costs in the treatment of this pathology [20][21][22].…”