Celastrol pretreatment as a therapeutic option against cisplatin-induced nephrotoxicity.

Celastrol is a natural bioactive compound extracted from the medicinal plant Tripterygium wilfordii Hook F. It exhibits immunosuppressive, anti-inflammatory, and antioxidant activities. Cisplatin is a commonly used chemotherapeutic drug in the treatment of a wide range of tumors. Although very effective therapeutically, it can cause nephrotoxicity leading to dose reduction or discontinuation of treatment. This study aims to clarify the therapeutic potential of celastrol in cisplatin-induced nephrotoxicity. The possible protective effects of celastrol pretreatment against cisplatin-induced oxidative stress and genotoxicity were investigated. A rat kidney epithelial cell line NRK-52E was pretreated with the desired concentrations of celastrol (200 nM, 100 nM, and 50 nM) for 24 h. The cells were treated with 50 µM cisplatin for a further 24 h to see whether cisplatin caused the same or less toxicity compared to the vehicle control group. Alkaline comet assay was performed for genotoxicity assessment. Genotoxicity evaluation revealed that celastrol caused a statistically significant reduction in DNA damage. Oxidative stress parameters were evaluated by measuring the glutathione (GSH) and protein carbonyl (PC) levels and also by measuring the enzyme activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) enzymes. Celastrol pretreatment increased the GSH content of the cells and ameliorated the protein carbonylation level. Likewise, celastrol pretreatment improved the GR and CAT activities. However, no significant difference was observed in GPx and SOD activities. In the light of these findings, celastrol treatment could be a therapeutic option to reduce cisplatin-induced nephrotoxicity. Further studies are needed for the clarification of its therapeutic potential.

Molecular biomarkers of oxidative stress and role of dietary factors in gasoline station attendants.

Exposure to benzene promotes oxidative stress through the production of ROS, which can damage biological structures with the formation of new metabolites which can be used as markers of oxidant/antioxidant imbalance. This study aims to assess modifications in circulating levels of advanced oxidation protein products (AOPP), advanced glycation end-products (AGE) and serum reactive oxygen metabolites (ROMs) in a group of gasoline station attendants exposed to low-dose benzene and to evaluate the influence of antioxidant food intake on these biomarkers of oxidative stress. The diet adopted by the population examined consisted of compounds belonging to the classes of terpenoids, stilbenes and flavonoids, notably resveratrol, lycopene and apigenin. Ninety one gasoline station attendants occupationally exposed to benzene and 63 unexposed male office workers were recruited for this study. Urinary trans, trans-muconic acid (t,t-MA) concentration, determined to assess individual exposure level, resulted significantly higher in exposed workers. In subjects exposed to benzene, we observed a significant increase (p < 0.001) in ROMs and AOPP levels, which were also negatively correlated with fruit and vegetables consumption. By contrast, AGE did not show a significant increase and consequently any relation with antioxidant food intake. Only ROMs, representing a global biomarker of oxidative status, resulted correlated to t,t-MA levels (p < 0.01), probably due to low-dose exposure. Increase of ROS induced by reactive benzene metabolites may promote specific biochemical pathways with a major production of AOPP, which seem to represent a more sensitive biochemical marker of oxidative stress in workers exposed to benzene compared to AGE. Furthermore, this is the first study demonstrating ROMs increment in subject exposed to benzene. These biomarkers may be useful for screening purposes in gasoline station workers and other subjects exposed to low-dose benzene. Moreover, a diet rich in fruits and vegetables demonstrated an inverse association with the levels of oxidative stress markers, suggesting a protective role of antioxidant food intake in workers exposed to oxidant agents.

Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.