Oxidative Stress and Its Consequences in the Blood of Rats Irradiated with UV: Protective Effect of Cannabidiol.

UVA/UVB radiation disturbs the redox balance of skin cells, and metabolic consequences can be transferred into the blood and internal tissues, especially after chronic skin exposure to UV radiation. Therefore, the aim of this study was to evaluate the effect of cannabidiol (CBD), an antioxidant and anti-inflammatory phytocannabinoid, on oxidative stress and its consequences in the blood of nude rats whose skin was exposed to UVA/UVB radiation for 4 weeks. It was shown that CBD penetrated the blood and in UVB-irradiated rats was preferentially located in the membranes of polymorphonuclear leukocytes, which promoted reduction of ROS generation and up-regulation of antioxidant ability by increasing the activity of glutathione reductase and thioredoxin reductase, while the level of reduced glutathione decreased by UV radiation. Consequently, reduction in UV-induced lipid peroxidation, assessed as 4-hydroxynonenal (4-HNE) and 8-isoprostane (8-isoPGF2α) as well as protein modifications, estimated as 4-HNE-protein adducts and protein carbonyl groups, was observed. CBD, by countering the UV-induced down-regulation of 2-arachidonylglycerol, promoted its antioxidant/anti-inflammatory effects by reducing CB1 and increasing PPARγ receptor activation and consequently ROS and TNF-α down-regulation. The results suggest that CBD applied topically to the skin minimizes redox changes not only at the skin level, but also at the systemic level.

Complexation of Bioelements and Toxic Metals by Polyphenolic Compounds - Implications for Health.

Nowadays, growing interest in the possibility of prophylactic and therapeutic use of plant products rich in biologically active compounds has been observed. Among them, special interest has been focused on polyphenol-rich products. Owing to the multidirectional favourable action of polyphenols, products rich in these compounds are recommended as functional food in the case of civilization diseases. Moreover, data from studies in animal models show that polyphenols may be a promising preventive/therapeutic strategy for xenobiotics, including toxic heavy metals. The protective impact of polyphenols against metal toxicity may be explained by the presence of many hydroxyl groups in the structure of these compounds, which are capable of forming complexes with metals preventing as a result from their gastrointestinal absorption and accelerating their elimination from the body with urine. However, it should be taken into account that polyphenols may bind not only ions of toxic metals, but also bioelements, what makes a risk of their shortage in the organism. This review provides an overview of implications for humans' and animals' health of complexation of bioelements and toxic metals by polyphenols present in the popular foodstuffs, including phenolic acids, cyanidin derivatives, delphinidin, quercetin, kaempferol, morin, epigallocatechin-3-gallate, and curcumin. Polyphenolic compounds capable of binding both necessary and toxic metals occur in commonly consumed products such as green tea, and some fruit and vegetables, including chokeberries, bilberries, and black currant fruit, grapes, and apples, as well as onion. The mechanisms of complexation of essential and toxic metals by polyphenols and possible implications of these for health are discussed.

RANKL/OPG system regulation by endogenous PTH and PTH1R/ATF4 axis in bone: Implications for bone accrual and strength in growing rats with mild uremia.

Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), and parathyroid hormone (PTH) play a central role in the regulation of bone turnover in chronic kidney disease (CKD), but their influence on bone mineral density (BMD) and strength remains unclear, particularly in children. We studied the clinical significance of OPG and RANKL in relation to PTH, femur weight, BMD, and bone biomechanical properties in growing rats after one month (CKD-1) and three months (CKD-3) of surgically-induced mild CKD. Gene expression of parathyroid hormone 1 receptor (PTH1R) and activating transcription factor 4 (ATF4), major regulators of anabolic PTH response in bone, was also determined. Serum PTH and bone PTH1R/ATF4 expression was elevated in CKD-3 compared with other groups, and it positively correlated with femur weight, BMD, and the biomechanical properties of the femoral diaphysis reflecting cortical bone strength. In contrast, bone RANKL/OPG ratios were decreased in CKD-3 rats compared with other groups, and they were inversely correlated with PTH and the other abovementioned bone parameters. However, the PTH-PTH1R-ATF4 axis exerted an unfavorable effect on the biomechanical properties of the femoral neck. In conclusion, this study showed for the first time an inverse association between serum PTH and the bone RANKL/OPG system in growing rats with mild CKD. A decrease in the RANKL/OPG ratio, associated with PTH-dependent activation of the anabolic PTH1R/ATF4 pathway, seems to be responsible for the unexpected, beneficial effect of PTH on cortical bone accrual and strength. Simultaneously, impaired biomechanical properties of the femoral neck were observed, making this bone site more susceptible to fractures.

The Association between Elevated Levels of Peripheral Serotonin and Its Metabolite - 5-Hydroxyindoleacetic Acid and Bone Strength and Metabolism in Growing Rats with Mild Experimental Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with disturbances in bone strength and metabolism. The alterations of the serotonergic system are also observed in CKD. We used the 5/6 nephrectomy model of CKD to assess the impact of peripheral serotonin and its metabolite- 5-hydroxyindoleacetic acid on bone biomechanical properties and metabolism in growing rats. The animals were sacrificed one and three months after nephrectomy. Biomechanical properties were determined on two different bone types: the cortical bone of the femoral diaphysis using three-point bending test and the mixed cortico-trabecular bone by the bending test of the femoral neck. Biomechanical tests revealed preserved cortical bone strength, whereas work to fracture (W) and yield load (Fy) of mixed cortico-trabecular bone were significantly lower in CKD compared to controls. Serum activity of alkaline phosphatase (ALP), a bone formation marker, and tartrate-resistant acid phosphatase (TRACP 5b) reflecting bone resorption, were similar in CKD and controls. ALP was associated with lower femoral stiffness and strength, and higher displacements and W. TRACP 5b was inversely associated with cortical Fu and W. The elevated peripheral serotonergic system in CKD was: inversely associated with stiffness but positively related to the displacements and W; inversely associated with cortical Fy but positively correlated with this parameter in cortico-trabecular bone; inversely associated with ALP in controls but positively correlated with this biomarker in CKD animals. In conclusion, this study demonstrates the distinct effect of mild degree of CKD on bone strength in rapidly growing rats. The impaired renal function affects the peripheral serotonin metabolism, which in turn may influence the strength and metabolism of bones in these rats. This relationship seems to be beneficial on the biomechanical properties of the cortico-trabecular bone, whereas the cortical bone strength can be potentially reduced.

[Select parameters of renal function in smokers in correlation with the exposure to cadmium]. / Badania nad wplywem palenia na wybrane parametry biochemiczne funkcji nerek w powiazaniu z narazeniem na kadm.

Cigarette smoke contains about 4000 chemical substances, including toxic metals such as cadmium. Smoking of 20 cigarettes a day results in inhalation an average 3.6-6.0 microg of cadmium. Due to nephrotoxic action of some components of tobacco smoke, and especially cadmium, the present study was aimed to evaluate of chosen parameters of kidney status in cigarette smokers in connection with estimation of cadmium concentration. The study was conducted in eighty-nine health and unexposed occupationally to cadmium inhabitants of Bialystok, smoking and non-smoking men and women at age 35-50. The smokers consumed 20 and more cigarettes per day for longer period than 10 years. Blood and morning urine were collected for analysis. In the urine samples, cadmium concentration (by atomic absorption spectrometry) and cotinine concentration (by gas chromatography with mass spectrometry), as an indicator of exposure to cigarette smoke, were determined. The kidney status was evaluated based on the urinary activities of lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzyme B (by colourimetrical method modified by Zwierz et al.) and concentrations of creatinine and urea in the serum (using diagnostic laboratory tests by POCh). The percentage reabsorption of phosphates was evaluated as well (TRP). Cadmium concentration in the urine of smoking women and men was higher compared to non-smokers, but there was no correlation between cadmium and cotinine concentrations in urine. In the smoking women, the urinary activity of NAG and TRP were higher than in non-smoking ones. In smokers, the activities of NAG and NAG-B in men and the activity of NAG-B in women were in the range of values noted in non-smokers, however the frequency of appearance of NAG and NAG-B activities above the limit of detection was higher compared to non-smokers. Cigarette smoking had no influence on the serum concentrations of creatinine and urea in both men and women and TRP in men. The results of the analysis of the urinary NAG and NAG-B activities in conjunction with the frequency of their appearance allow concluding that cigarette smoke might lead to an occurrence of early changes in proximal tubules of men and women.