Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells.

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.

Rutin, a Flavonoid That Is a Main Component of Saussurea involucrata, Attenuates the Senescence Effect in D-Galactose Aging Mouse Model.

Saussurea involucrata (Kar. et Kir.), known as the snow lotus, grows in the Tian Shan and A'er Tai areas of China. It has recently been reported that the ethyl acetate extract of S. involucrata (SI-2) can inhibit proliferation and induce apoptosis in PC-3 human prostate cancer cells. This study investigated the protective effect of ethyl acetate extract of S. involucrata (SI-2) or rutin, a flavonoid extracted from ethyl acetate extract of S. involucrata (SI-2), on D-galactose- (D-gal-) induced brain injury in mice. Administering SI-2 or rutin (30 mg/kg/d and 30 mg/kg/d) for 6 weeks, concomitant with D-gal injection, significantly increased superoxide dismutase and glutathione peroxidase activities and decreased the MDA level in plasma. Furthermore, the result showed that the percentages of cleaved caspase-3 and PARP in the D-gal-treated mice were much higher than those in the control. Pretreatment using SI-2 or rutin decreased the expression of cyclooxygenase-2 via downregulation of NF-kappaB, resulting in a decrease in lipid peroxidation. Furthermore, our results also showed that oral administration of rutin to these mice significantly improved behavioral performance in a step-through passive avoidance task and these results suggest that SI-2 or rutin exerts potent antiaging effects on D-gal in mice via antioxidative mechanisms.

Antioxidant vitamins promote anticancer effects on low-concentration methotrexate-treated glioblastoma cells via enhancing the caspase-3 death pathway.

Vitamin C and vitamin E are well-known antioxidant vitamins, both of which are also applied as adjunct treatments for cancer therapy. Methotrexate (MTX) is a clinical drug that is used widely for rheumatoid arthritis and cancer treatment. Human glioblastoma multiforme (GBM) is an aggressive malignant brain tumor; the mean survival time for GBM patients is <2 years with traditional therapies. Developing and investigating novel treatments are important for clinical GBM therapy. Therefore, the aim of this study was to investigate whether combined treatment with vitamin C/E and MTX can display anticancer activities on GBM. Our studies showed that MTX displays anticancer effects on GBM in a dose-dependent manner, while vitamins C and E are not cytotoxic to glioblastoma. Importantly, this study showed that vitamins C and E can promote anticancer effects on low-concentration methotrexate-treated glioblastoma. Additionally, this study suggested that MTX alone or combined with vitamins C/E inhibits GBM cell growth via the caspase-3 death pathway.

Acetaminophen induces JNK/p38 signaling and activates the caspase-9-3-dependent cell death pathway in human mesenchymal stem cells.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. Generally, the therapeutic dose of APAP is clinically safe, however, high doses of APAP can cause acute liver and kidney injury. Therefore, the majority of previous studies have focussed on elucidating the mechanisms of APAP-induced hepatotoxicity and nephrotoxicity, in addition to examining ways to treat these conditions in clinical cases. However, few studies have reported APAP-induced intoxication in human stem cells. Stem cells are important in cell proliferation, differentiation and repair during human development, particularly during fetal and child development. At present, whether APAP causes cytotoxic effects in human stem cells remains to be elucidated, therefore, the present study aimed to investigate the cellular effects of APAP treatment in human stem cells. The results of the present study revealed that high-dose APAP induced more marked cytotoxic effects in human mesenchymal stem cells (hMSCs) than in renal tubular cells. In addition, increased levels of hydrogen peroxide (H2O2), phosphorylation of c-Jun N-terminal kinase and p38, and activation of caspase-9/-3 cascade were observed in the APAP-treated hMSCs. By contrast, antioxidants, including vitamin C reduced APAP-induced augmentations in H2O2 levels, but did not inhibit the APAP-induced cytotoxic effects in the hMSCs. These results suggested that high doses of APAP may cause serious damage towards hMSCs.