Tangeretin protects renal tubular epithelial cells against experimental cisplatin toxicity

Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats.Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined.Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury.Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent

Evaluation of the serum concentrations of albumin and uric acid as a biomarker in patients with Parkinson\'s disease

Background: Parkinson's disease (PD) is a neurological disorder in which dopamine-producing neurons are destroyed. This disease is associated with aging. Our aim in this study was to measure the serum concentrations of albumin and uric acid (UA) as a biomarker for PD detection. Materials and Methods: In this case-control study, we recruited 40 Parkinson patients and 40 healthy individuals. Blood samples (5 ml) were collected from both groups and the serum was isolated. Serum albumin and UA levels were measured, and the data was analyzed by SPSS software, and graphs were prepared using Graphpad Prism. Results: Our results showed that the serum levels of albumin were significantly higher in the control group (5.69 ± 2.51 g/dl) compared to the patient group (4.12 ± 1.60 g/dl) (p˂ 0.001). On the other hand, the serum concentrations of UA in the control group (5.18 ± 1.28 mg/dl) were not statistically significantly different in comparison with the patient group (5.01 ± 1.34 mg/dl) (p= 0.56). The ROC analysis used to evaluate the diagnostic value of biomarkers for PD. Albumin was shown to have a high capability for separating patients from healthy subjects, with an area under the ROC curve 0.85, sensitivity 60% and specificity 97%. Conclusion: The findings of this study indicate that serum albumin levels in patients with PD are lower than healthy subject, and maybe in the future this can be used as diagnostic criteria

TGF-β1 receptor blockade attenuates unilateral ureteral obstruction-induced renal fibrosis in C57BL/6 mice through attenuating Smad and MAPK pathways

Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal fibrosis through Smad dependent and/or Smad independent pathways. Thirty-five male C57BL/6 mice were divided into five groups of seven each; sham, unilateral ureteral obstruction (UUO), UUO+galunisertib (150 and 300 mg/kg/day), galunisertib (300 mg/kg/day). The UUO markedly induced renal fibrosis and injury as indicated by renal functional loss, increased levels of collagen Iα1, fibronectin and α-SMA; it also activated both the Smad 2/3 and MAPKs pathways as indicated by increased levels of TGF-β1, p-Smad 2, p-Smad 3, p-p38, p-JNK and p-ERK. These UUO-induced changes were markedly attenuated by oral administration of galunisertib, the TGFβRI small molecule inhibitor. In conclusion, we demonstrated that TGF-β1 receptor blockade can prevent UUO-induced renal fibrosis through indirect modulation of Smad and MAPKs signaling pathways and may be useful as a therapeutic agent in treatment and/or prevention of renal fibrosis