The role of ginger's extract and N-acetylcysteine against docetaxel-induced oxidative stress and genetic disorder.

Oxidative stress plays a prominent role in expanding toxicity and various diseases. This study investigated the potential protective effects of ginger (Zingiber officinale) rhizome extract and NAC on docetaxel induced genotoxicity and oxidative stress. The antioxidant power of NAC and ginger extract on the genetic toxicity induced by docetaxel was assessed by micronucleus test. The ROS test with DCFH reagent was used to assess the reactive oxygen species. The thiobarbituric acid method was used to evaluate the amount of MDA produced by docetaxel. The amounts of phenol and flavonoids in the ginger extracts were also evaluated. The amount of phenol in the ginger extract was 0.886 mg of gallic acid per gram of dry extract. The amount of flavonoids were 0.242 mg/mL of quercetin per gram of dry extract. As shown by the micronucleus results, concentrations of 100 and 500 µM NAC and all concentrations of the ginger extract significantly reduced the number of micronuclei produced by docetaxel. On the other hand, the results of oxidative stress tests (ROS and LPO) showed that docetaxel in HGF cells increased the production of ROS and LPO, and the concentrations of ginger extract and NAC decreased oxidative stress in HGF cells in a dose-dependent manner. The results indicate that using these two antioxidants helps inhibit genetic toxicity and oxidative stress caused by docetaxel.

Treatment of electrical wrist stimulation reduces chemotherapy-induced neuropathy and ultrasound vocalization via modulation of spinal NR2B phosphorylation.

Docetaxel, a chemotherapeutic agent used to treat breast cancer, produces a robust painful neuropathy that is aggravated by mechanical and thermal stimuli. This study was undertaken to investigate the analgesic effects of electrical stimulation on docetaxel-induced neuropathic pain in mice and to identify associated changes in ultrasound vocalizations. Peripheral neuropathy was induced with intraperitoneally injected docetaxel (5 mg/kg) on 3 times every 2 days in male ICR mice. Electrical wrist stimulation was administered and pain behavior signs were evaluated by von Frey filaments and thermal stimulation on the hind paw. Ultrasound vocalizations were measured using ultrasound microphones, after electrical stimulation. After mice developed docetaxel-induced neuropathic pain behavior, an electrical stimulation temporarily attenuated mechanical allodynia and thermal hyperalgesia. In formalin and NMDA test, pain-induced mice showed increases in 10-30 kHz ultrasound vocalizations, but not in 30-50 and 50-80 kHz vocalizations. Treatment with docetaxel selectively increased 10-30 kHz ultrasound vocalizations, whereas electrical stimulation caused a meaningful decrease. Moreover, electrical stimulation suppressed the docetaxel-enhanced phosphorylation of the NMDA receptor NR2B subunit in the spinal dorsal horn. These results of the analgesic effect of electrical stimulation in chemotherapy-induced neuropathy could potentially provide a new method to treat and manage peripheral neuropathy in patients with cancer.

Effect of the Phragmitis Rhizoma Aqueous Extract on the Pharmacokinetics of Docetaxel in Rats.

BACKGROUND: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. AIM AND OBJECTIVE: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague-Dawley rats. MATERIALS AND METHODS: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. RESULTS: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). CONCLUSION: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.