Influence of cellular redox environment on aryl hydrocarbon receptor ligands induced melanogenesis.

Many environmental pollutants, natural compounds, as well as endogenous chemicals exert their biological/toxicological effects by reacting with the aryl hydrocarbon receptor (AhR). Previous evidence shed new light on the role of AhR in skin physiology by regulating melanin production. In this study, we investigated the effect of oxidative imbalance induced by AhR ligands on the melanogenesis process in B16 murine melanoma cells. Exposure to 6-formylindolo[3,2-b] carbazole (FICZ) or benzo-α-pyrene (BαP) led to enhanced expression of CTNNB1, MITF, and TYR genes following increased tyrosinase enzyme activity and melanin content in an AhR-dependent manner. Analysis of the presence of reactive oxygen species (ROS) as well as reduced glutathione (GSH) / oxidized glutathione (GSSG) ratio revealed that treatment with AhR ligands is associated with oxidative stress which can be ameliorated with NAC (N-acetyl cysteine) or diphenyleneiodonium chloride (DPI). On the other hand, NAC and DPI enhanced melanogenesis induced by AhR ligands by reducing the level of ROS. We have shown for the first time that a cellular redox status is a critical event during AhR ligand-induced melanogenesis.

The Pattern of Cyclosporine Nephrotoxicity and Urinary Kidney Injury Molecule 1 in Allogenic Hematopoietic Stem Cell Transplant Patients.

OBJECTIVES: The typical immunosuppressive regimen of hematopoietic stem cell transplant includes cyclosporine. However, cyclosporine nephrotoxicity is a concern. We studied cyclosporine nephrotoxicity epidemiology in hematopoietic stem cell transplant patients and compared the pattern and urinary levels of the KIM-1 kidney injury molecule versus serum and urine creatinine levels. MATERIALS AND METHODS: The study covered 10 months at Namazi Hospital, Shiraz, Iran. All patients met the following criteria: > 15 years old, received allogenic hematopoietic stem cell transplant without history of acute or chronic kidney disease, and scheduled for at least 1 week of cyclosporine treatment. Urinary and serum levels of creatinine, urea, sodium, potassium, magnesium, and the KIM-1 kidney injury molecule were measured on days 0, 3, 5, 7, 10, and 14 of cyclosporine treatment. RESULTS: Of 42 patients, one-third developed cyclosporine nephrotoxicity (30.95%), and median onset time was 15 days. Hypokalemia and hypomagnesemia were reported in 76.2% and 53.4% of the cohort, respectively. None of the demographic, clinical, and paraclinical parameters was significantly associated with cyclosporine nephrotoxicity. Median duration of hospital stay for patients with cyclosporine nephrotoxicity (41 days) was significantly higher (P < .001) than those without nephrotoxicity (29 days). Area under the curve for receiver operating characteristic showed that accuracy of serum creatinine (0.267; 95% CI, 0.11-0.43) at day 0 of cyclosporine treatment was significantly lower (P = .017) than the accuracy of urine creatinine (0.477; 95% CI, 0.28-0.67) and urine levels of the KIM-1 kidney injury molecule (0.594; 95% CI, 0.41-0.78). CONCLUSIONS: Cyclosporine nephrotoxicity is a common adverse effect in the setting of hematopoietic stem cell transplant and occurs mostly within the first 2 weeks of cyclosporine treatment. Urine KIM-1 kidney injury molecule measurement had no overall superiority and no improved accuracy over serum or urine creatinine measurements for prediction or detection of cyclosporine nephrotoxicity.

The potential effects of anabolic-androgenic steroids and growth hormone as commonly used sport supplements on the kidney: a systematic review.

BACKGROUND: Anabolic-androgenic steroids and growth hormone are among the most commonly used supplements by sportsmen and sportswomen. The aim of this systematic review is to collect and report available data about renal safety of anabolic-androgenic steroids and growth hormone (GH). METHODS: The search strategy was in accordance with the PRISMA guideline. Seven databases such as Scopus, Medline, Embase, and ISI Web of Knowledge were searched using keywords, such as "growth hormone", "anabolic-androgenic steroids", and "kidney injury". Articles published from 1950 to December 2017 were considered. Randomized clinical trials, prospective or retrospective human studies, case series as well as case reports, and experimental (in vivo) studies were included. Twenty one clinical and experimental articles were selected (12 for anabolic-androgenic steroids and 9 for GH). RESULTS: Anabolic-androgenic steroids can affect the kidney in different aspects. They can induce or aggravate acute kidney injury, chronic kidney disease, and glomerular toxicity. These adverse effects are mediated through pathways such as stimulating renin-angiotensin-aldosterone system, enhancing the production of endothelin, producing reactive oxygen species, over-expression of pro-fibrotic and pro-apoptotic mediators (e.g., TGF-ß1), as well as inflammatory cytokines (e.g., TNF-α, IL-1b, and IL-6). Although GH may affect the kidney in different aspects, such as size, glomerular filtration rate, and tubule functions, either directly or indirectly, there is no conclusive clinical evidence about its detrimental effects on the kidney in athletes and body builders. CONCLUSION: Evidence regarding effects of anabolic-androgenic steroids exists; However, GH's exact effect on the kidney at doses used by athletes and body builders has not yet been clarified. Cohort clinical studies with long-term follow-up are warranted in this regard.

Pattern and associated factors of adherence to immunosuppressive medications in kidney transplant recipients at a referral center in Iran.

Purpose: Ever increasing number of patients who receive kidney transplantation as a therapeutic option, approaches to increase graft survival as well as to identify factors that reduce the treatment outcomes should be taken into account. One of the heightened concerns after transplantation is non-adherence to immunosuppressive medications, which increases the risk of kidney failure or even rejection. The aim of this study was to evaluate factors associated with immunosuppressant medications adherence in kidney transplant recipients. Patients and methods: Data were collected from 100 eligible kidney transplant patients referring to Shiraz Motahhari clinic and a private office of an attending nephrologist during 18 months. Adherence to immunosuppressive medications was assessed by Basel assessment of adherence to immunosuppressive medication scale at 2 time points. Results: According to the findings, 55% of patients did not adhere to their post-transplantation immunosuppressive medications. The rate of adherence to immunosuppressive medications was not either statistically or clinically significant between time points zero and six months. None of the investigated factors including demographic, clinical and social-economical-cultural factors were significantly associated with patients' adherence to immunosuppressive regimen. Furthermore, there was no statistically significant association between immunosuppressive medication adherence and acute kidney rejection. Conclusion: The rate of non-adherence to immunosuppressive medications was high. These data can be exploited by both physicians and policymakers to improve the rate of adherence to immunosuppressive medications amongst kidney transplant recipients.

Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications.

Prebiotics are a group of nutrients that are degraded by gut microbiota. Their relationship with human overall health has been an area of increasing interest in recent years. They can feed the intestinal microbiota, and their degradation products are short-chain fatty acids that are released into blood circulation, consequently, affecting not only the gastrointestinal tracts but also other distant organs. Fructo-oligosaccharides and galacto-oligosaccharides are the two important groups of prebiotics with beneficial effects on human health. Since low quantities of fructo-oligosaccharides and galacto-oligosaccharides naturally exist in foods, scientists are attempting to produce prebiotics on an industrial scale. Considering the health benefits of prebiotics and their safety, as well as their production and storage advantages compared to probiotics, they seem to be fascinating candidates for promoting human health condition as a replacement or in association with probiotics. This review discusses different aspects of prebiotics, including their crucial role in human well-being.

The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders.

One of the major concerns about taking amino acid supplements is their potential adverse effects on the kidney as a major organ involved in the metabolism and excretion of exogenous substances. The aim of this study is to review available data about renal safety of the most prominent amino acid supplements including L-arginine, glutamine and also L-carnitine as well as creatine (as amino acid derivatives) in athletes and bodybuilders. The literature was searched by keywords such as "L-carnitine", "L-arginine", "glutamine", and "kidney injury" in databases such as Scopus, Medline, Embase, and ISI Web of Knowledge. Articles published from 1950 to December 2017 were included. Among 3171, 5740, and 1608 records after primary search in the relevant databases, 8, 7, and 5 studies have been finally included, respectively, for L-carnitine, L-arginine, and glutamine in this review. Arginine appears to have both beneficial and detrimental effects on kidney function. However, adverse effects are unlikely to occur with the routine doses (from 3 to >100 g/day). The risks and benefits of L-carnitine on the athletes' and bodybuilders' kidney have not been evaluated yet. However, L-carnitine up to 6000 mg/day is generally considered to be a safe supplement at least in healthy adults. Both short-term (20-30 g within a few hours) and long-term (0.1 g/kg four times daily for 2 weeks) glutamine supplementation in healthy athletes were associated with no significant adverse effects, but it can cause glomerulosclerosis and serum creatinine level elevation in the setting of diabetic nephropathy. Creatine supplementation (ranged from 5 to 30 g/day) also appears to have no detrimental effects on kidney function of individuals without underlying renal diseases. More clinical data are warranted to determine the optimal daily dose and intake duration of common supplemental amino acids associated with the lowest renal adverse effects in sportsmen and sports women.

Potential Adverse Effects of Creatine Supplement on the Kidney in Athletes and Bodybuilders.

INTRODUCTION: Nowadays, creatine is one of the most common oral supplements used by professional athletes for boosting their strength and muscle mass. In this review, we collect available experimental and clinical data about renal safety of both short-term and long-term use of creatine. MATERIALS AND METHODS: Scientific literature was critically searched by keywords "creatine," "renal insufficiency," and "renal dysfunction" and their synonyms in medical databases (Scopus, MEDLINE, EMBase, and ISI Web of Knowledge). Overall, 19 relevant clinical and experimental articles were selected for this review. RESULTS: Short- and long-term creatine supplementations (range, 5 days to 5 years) with different doses (range, 5 g/d to 30 g/d) had no known significant effects on different studied indexes of kidney function such as glomerular filtration rate at least in healthy athletes and bodybuilders with no underlying kidney diseases. In addition, although short-term (range, 5 days to 2 weeks) high-dose oral creatine supplementation (range, 20 g/d to 0.3 g/kg/d) stimulated the production of methylamine and formaldehyde (as potential cytotoxic metabolites of creatine) in the urine of healthy humans, there was currently no definite clinical evidence about their adverse effects on the kidney function. CONCLUSIONS: Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.