Anticancer and cytotoxic effects of troxerutin on HeLa cell line: an in-vitro model of cervical cancer

Cervical cancer is one of the grave uterine tumors which leads to death in women worldwide. Troxerutin (TRX) as a bioflavonoid compound has many pharmacological effects such as anti-neoplastic, radioprotective, and anti-cancer. The present study was designed to examine the cytotoxic effect of TRX on human HeLa tumor cells. Human HeLa cells were cultured and treated with different doses of TRX (20�640 mg/ml) to evaluate the effective half-maximal inhibitory concentration (IC50) after 24 h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used for cell proliferation assay. Also, the Bax, Bcl-2, cleaved caspase-3, and tumor necrosis factor-α (TNF-α) protein expression levels were detected with immunoblotting analysis. The malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured via their commercial kits. Data were analyzed using one-way ANOVA. The result showed that TRX at 320 mg/ml concentration (IC50) has a growth inhibitory effect against HeLa cells at 24 h treatment (P � 0.01). Moreover, it increased the MDA concentration and also decreased the GPx and SOD activity levels at 320 mg/ml concentration versus control (P < 0.001). Also, TRX significantly up-regulated the Bax, cleaved caspase-3 and TNF-α proteins expression levels (P < 0.01) and down-regulated the Bcl-2 protein expression in HeLa tumor cells at 320 mg/ml concentration compared to control (P < 0.05). Our study showed that 24 h of treatment with TRX (320 mg/ml) has apoptotic and growth inhibitory effects against HeLa cells. It can induce inflammation (at least via up-regulating the TNF-α protein expression) and oxidative stress in human HeLa cells. © 2020, Springer Nature B.V

Changes in the gene expression of estrogen receptors involved in the protective effect of estrogen in rat's trumatic brain injury

It has been demonstrated that estradiol has neuroprotective effects after traumatic brain injury (TBI) in female rats. Since estrogen receptors have an important role in estradiol effects at the cellular level and the exact mechanism(s) of estradiol-induced neuroprotection has not yet been fully clarified, the present study was designed to determine the changes in the levels of estrogen receptors mRNAs and proteins involved in this phenomenon. All experiments were carried out on female Wistar rats. The brain edema and blood-brain-barrier (BBB) disruption were assessed. The TBI method was diffuse type and induced by the Marmarou method. Semiquantitative RT-PCR and immunoblotting were used to assess ERα and ERβ gene expression. The data showed that the level of brain water content was significantly increased in TBI group. The increased water content was significantly attenuated in estradiol-treated (1mg/kg) TBI rats. Disruption of BBB after TBI was significantly inhibited just by estradiol treatment. Estrogen-treated animals showed a significant increase in ERα mRNA (18%) and protein (35%) levels in the brain tissue. Furthermore, in the brain-injured rats the levels of ERβ mRNA were lower than those in control rats. Following estrogen treatment, the protein levels of ERβ were closed to those in control group. In conclusion, the data demonstrate that estrogen treatment can protect brain against traumatic brain injury. Estrogen treatment increases ER mRNA and protein levels which were coincident with its protective effects. It seems that such phenomenon participates in the induction of neuroprotective effects of estrogen. This article is part of a Special Issue entitled 1618

Activators of SIRT1 in the kidney and protective effects of SIRT1 during acute kidney injury (AKI) (effect of SIRT1 activators on acute kidney injury)

Acute kidney injury (AKI) is a complex disorder and a clinical condition characterized by acute reduction in renal function. If AKI is not treated, it can lead to chronic kidney disease, which is associated with a high risk of death. SIRT1 (silent information regulator 1) is an NAD-dependent deacetylase. This enzyme is responsible for the processes of DNA repair or recombination, chromosomal stability, and gene transcription. This enzyme also plays a protective role in many diseases, including AKI. In this study, we review the mechanisms that mediate the protective effects of SIRT1 on AKI, including SIRT1 activators. © 2021, Japanese Society of Nephrology