Effects of Letrozole Treatment and Vitamin C Supplementation on Morphology, Endoplasmic Reticulum Stress, Programmed Cell Death, and Oxidative Stress in the Small Intestine of Adult Male Rats.

Estrogens are hormones that play an important role in the digestive tract, including in men. Letrozole is an inhibitor of cytochrome P450 aromatase, an enzyme converting androgens to estrogens. The use of letrozole may cause oxidative stress and endoplasmic reticulum stress in the cells. Factors modulating cellular stress may include vitamin C. The purpose of this study was to examine whether letrozole and/or vitamin C supplementation can affect the morphology of the small intestine, the parameters of endoplasmic reticulum stress, programmed cell death markers, and oxidative damage. Three-month-old male rats were divided into four groups and treated with the following: (I) CTRL-water; (II) CTRL+C-L-ascorbic acid; (III) LET-letrozole; and (IV) LET+C-letrozole + L-ascorbic acid. The morphometrical measurements included epithelial thickness, crypt and lumen area, crypt perimeter, nuclei number in the crypt, and the cell size of crypts. The expression levels of PERK, caspase-3, and catalase were determined. Significant differences in the morphometrical measurements and immunoexpression were observed. This may indicate that chronic treatment with letrozole can affect morphology and induce ER stress, oxidative stress, and programmed cell death in the epithelial cells of the small intestine of adult male rats. Vitamin C supplementation exerts an effect on some parameters of the molecular processes.

The Effect of the Gut Microbiota on Transplanted Kidney Function.

The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.

Serum Selenium, Iron, Zinc, and Copper Concentrations in Renal Transplant Recipients Treated with Mycophenolate Mofetil.

There are data available in the literature on bioelement concentrations in the serum of various groups of patients; however, very little is known about the serum concentration of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu) in renal transplant patients treated with immunosuppressive drugs, including mycophenolate mofetil (MMF). Monitoring of serum bioelement concentrations in renal transplant recipients is of profound importance, as the proper bioelement levels seem to prolong the normal function of the transplanted organ. Thus, the aim of this current study was to examine and carry out comparative analysis involving serum concentrations of Se, Fe, Cu, and Zn of renal transplant recipients treated with MMF and without MMF. The material consisted of blood samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in the northwestern Poland. Serum Se, Fe, Cu, and Zn levels were quantified by inductively coupled mass spectroscopy (ICP-MS). Taking into account all patients, MMF increases Cu level. Cu and Fe concentrations were significantly higher in women treated with MMF; in group of younger patients treated with MMF, Se level was significantly lower comparing with those whose regimen did not include MMF. Additionally, MMF in combination with prednisone increased Se concentration in blood of transplant recipients. Our study highlights that trace elements should be monitored to allow for an early detection of trace elements deficits, which can easily be corrected for by an adjusted diet or supplemental intake.

Arsenic and Selenium Profile in Erythrocytes of Renal Transplant Recipients.

Arsenic and selenium elements play extremely important roles in organisms. Too high As concentration in blood may lead to functional disorders within organs, including cancer. Arsenic is designated as a Group 1 human carcinogen by the International Agency for Research on Cancer that has established causal role of arsenic in cancers of the urinary bladder, lung, and skin in humans. In contrast, Se is believed to be the antioxidant trace element that is important in the biological defense against oxidative damage. We tested the hypothesis that immunosuppressive treatment based on mycophenolate mofetil (MMF), that is one of the most commonly used drug by renal transplant recipients, affects arsenic and selenium concentration in erythrocytes of renal transplant recipients. Current research was undertaken due to the fact that there are few studies on the concentration of chemical elements in the erythrocytes in kidney patients receiving immunosuppressive drugs. Monitoring of the concentration of chemical elements in the blood in patients who underwent kidney transplantation could be helpful, since chemical elements play an important role in many biological processes and it seems to be crucial in the prevention of cancer to which renal transplant recipients are more often exposed.The material consisted of blood from 115 renal transplant recipients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in northwestern Poland. Arsenic and selenium levels in erythrocytes were quantified by inductively coupled mass spectroscopy.Men MMF+ had significantly higher As concentration than men MMF-. Se concentration was significantly higher in younger patients compared with older patients. The patients with lower creatinine level who used MMF had significantly higher As than MMF- patients. Patients whose therapy was based on MMF, cyclosporine A and glucocorticosteroids exhibited significantly higher concentration of As compared with patients whose regimen was based on MMF, tacrolimus, and glucocorticosteroids.This is the first study that demonstrates that regimen based on mycophenolate mofetil affects As and Se concentrations in erythrocytes in renal transplant recipients.