Chronic kidney disease (CKD) is a debilitating pathology with various causal factors, culminating in end stage renal disease (ESRD) requiring dialysis or kidney transplantation. The progression of CKD is closely associated with systemic inflammation and oxidative stress, which are responsible for the manifestation of numerous complications such as malnutrition, atherosclerosis, coronary artery calcification, heart failure, anemia and mineral and bone disorders, as well as enhanced cardiovascular mortality. In addition to conventional therapy with anti-inflammatory and antioxidative agents, growing evidence has indicated that certain minerals, vitamins and plant-derived metabolites exhibit beneficial effects in these disturbances. In the current work, we review the anti-inflammatory and antioxidant properties of various agents which could be of potential benefit in CKD/ESRD. However, the related studies were limited due to small sample sizes and short-term follow-up in many trials. Therefore, studies of several anti-inflammatory and antioxidant agents with long-term follow-ups are necessary.

The intestines are recognized as the main source of chronic inflammation in chronic kidney disease (CKD) and, among other cells, macrophages are involved in modulating this process as well as in the impaired immune response which also occurs in CKD patients. In this study, we evaluated the effect of Indoxyl Sulfate (IS), a protein bound uremic toxin poorly eliminated by hemodialysis, on inflammatory, oxidative stress and pro-apoptotic parameters, at the intestinal level in mice, on intestinal epithelial cells (IEC-6) and on primary murine peritoneal macrophages. C57BL/6J mice were treated with IS (800 mg/kg i.p.) for 3 or 6 h and histopathological analysis showed that IS induced intestinal inflammation and increased cyclooxygenase-2 (COX-2), nitrotyrosine and Bax expression in intestinal tissue. In IEC-6 cells, IS (125–1000 µM) increased tumor necrosis factor-α levels, COX-2 and inducible nitric oxide synthase expression and nitrotyrosine formation. Moreover, IS increased pro-oxidant, pro-inflammatory and pro-apoptotic parameters in peritoneal macrophages from IS-treated mice. Also, the serum concentration of IS and pro-inflammatory levels of cytokines resulted increased in IS-treated mice. Our results indicate that IS significantly contributes to affect intestinal homeostasis, immune response, and to induce a systemic pro-inflammatory state thus highlighting its potential role as therapeutic target in CKD patients.

5-Fluorouracil (5-FU) is a pyrimidine analogue used as an antineoplastic agent to treat multiple solid tumors. Despite its use and efficacy, it also has important side effects in healthy cells, including skin reactions, related to its pro-oxidant and pro-inflammatory potential. Although there are numerous remedies for chemotherapy-induced skin reactions, the efficacy of these treatments remains limited. In this study we focused on the effects of pomegranate (Punica granatum L.) juice extract (PPJE) on the oxidative and inflammatory state in 5-FU-treated human skin keratinocytes (HaCaT). The obtained results showed that PPJE significantly inhibited reactive oxygen species release and increased the cellular antioxidant response, as indicated by the increased expression of cytoprotective enzymes, such as heme oxygenase-1 and NAD(P)H dehydrogenase [quinone] 1. In these experimental conditions, PPJE also inhibited nitrotyrosine formation and 5-FU-induced inflammatory response, as indicated by the reduced cytokine level release. Moreover, PPJE inhibited nuclear translocation of p65-NF-κB, a key factor regulating the inflammatory response. In 5-FU-treated HaCaT cells PPJE also inhibited apoptosis and promoted wound repair. These results suggest a potential use of PPJE as an adjuvant in the treatment of the oxidative and inflammatory state that characterizes chemotherapy-induced skin side effects.

Inflammation and oxidative stress are always more recognized as responsible for chronic disease at the intestinal level. Currently, a growing interest is addressed to the discovery of diet-derived products which have anti-inflammatory and antioxidant properties. This work aims to characterize the pharmacological potential of dehydrated potatoes. For this purpose, a simulated gastrointestinal digestion was carried out. The bioaccessible peptides were fractionated on the basis of their molecular weight and tested on intestinal epithelial cells (IEC-6) under oxidative and inflammatory conditions. Our results demonstrate that the tested peptide fractions were able to significantly inhibit tumor necrosis factor-α release and cycloxygenase-2 and inducible nitric oxide synthase expression. The tested peptides also showed significant antioxidant activity, being able to both reduce reactive oxygen species (ROS) release, also from mitochondria, and nitrotyrosine formation, and increase the antioxidant response by heme oxygenase-1 and superoxide dismutase expression. Moreover, the peptide fractions were able to significantly increase the wound repair in IEC-6. The obtained results indicate the anti-inflammatory and antioxidant potential of dehydrated potatoes at the intestinal level.

Intestinal epithelial cells (IECs) play a pivotal role in maintaining intestinal homeostasis. Different noxious agents, among them also anticancer therapies, can impair intestinal epithelial integrity triggering inflammation and oxidative stress. A frequent complication of chemotherapy is gastrointestinal mucositis, strongly influencing the effectiveness of therapy, increasing healthcare costs, and impairing patients’ quality of life. Different strategies are used to treat gastrointestinal mucositis, including products from natural sources. Our study focused on the effect of pomegranate (Punica granatum L.) juice extract on IEC-6 cells, both during inflammatory conditions and following treatment with 5-fluorouracil (5-FU). The polyphenolic profile of pomegranate juice was characterized in detail by Online Comprehensive two dimensional Liquid Chromatography-Mass Spectrometry. The evaluation of pomegranate juice extract in IEC-6 indicates a significant inhibition in proinflammatory factors, such as cytokines release, cyclooxygenase-2 and inducible nitric oxide synthase expression, and nitrotyrosine formation. Pomegranate also inhibited oxidative stress and adhesion protein expression. In 5-FU-treated IEC-6, pomegranate also inhibited both inflammatory and oxidative stress parameters and apoptosis. It promoted wound repair and tight junction expression. These results suggest a potential use of pomegranate as an adjuvant in the treatment of intestinal inflammatory and oxidative stress states, which also occur during chemotherapy-induced mucositis.

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.