Safety, Tolerance, and Metabolism of Broccoli Sprout Glucosinolates and Isothiocyanates: A Clinical Phase I Study

Shapiro, Theresa A.; Fahey, Jed W.; Dinkova‐Kostova, Albena T.; Holtzclaw, W. David; Stephenson, Katherine K.; Wade, Kristina L.; Ye, Lingxiang; Talalay, Paul

doi:10.1207/s15327914nc5501_7

Cited by 294 publications

(299 citation statements)

References 20 publications

Supporting

Mentioning

282

Contrasting

Unclassified

Order By: Relevance

“…In this study, we found that sulforaphane has strong analgesic effects on SNT-induced pain hypersensitivity, suggesting additional therapeutic potential for this molecule in the treatment of neuropathic pain. Its analgesic efficacy observed postinjury and its safety verified in a clinical trial (24) further underscore its therapeutic potential.…”

Section: Discussionmentioning

confidence: 87%

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

Kim

You

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

206

198

View full text Add to dashboard Cite

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain.spinal nerve transection | sulforaphane D amage to the peripheral nerve often results in abnormal chronic pain and pain hypersensitivity that are generally referred to as "neuropathic pain." It is known that hypersensitivity of pain-transmission neurons in the spinal cord is involved in the development of neuropathic pain, and this process has been referred to as central sensitization (1). Various pathological events are reported to precede central sensitization. These include, but are not limited to, p38 activation in spinal cord microglia and subsequent proinflammatory cytokine expression, NMDA receptor phosphorylation in spinal cord neurons, and altered expression of ion channels on neurons (2-5). In addition, a series of studies have implied that production of reactive oxygen species (ROS) in the spinal cord is involved in the induction of neuropathic pain. For example, systemic injection of ROS scavengers, such as phenyl-N-tert-butylnitrone (PBN) and 5,5-dimethylpyrroline-N-oxide (DMPO), relieved spinal nerve ligation-induced pain hypersensitivity in rats (6). In addition, spinal nerve ligation-induced phosphorylation of the NMDA receptor subunit 1 (NR1) in dorsal horn neurons was attenuated by ROS scavengers (7). These results suggested that ROS are critically involved in the development and maintenance of neuropathic pain; however, the exact primary source of ROS production has remained elusive.Recently, a study using the mitochondrial ROS detector MT-Red showed that ROS are generated in the mitochondria of dorsal horn neurons (8). Production of mitochondrial ROS by intrathecal injection of the electron transport complex inhibitors...

show abstract

Section: Discussionmentioning

confidence: 87%

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

Kim

You

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

206

198

View full text Add to dashboard Cite

show abstract

“…Glucosinolates and isothiocyanates could be interesting candidates for such strategies. They have been investigated in clinical trials with no significant reported toxicity (31)(32)(33). However, only sulforaphane precursors such as purified glucosinolates or broccoli sprouts and not sulforaphane are currently in intervention trials because sulforaphane is highly unstable in its free form (34).…”

Section: Introductionmentioning

confidence: 99%

Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy

Cipolla¹,

Mandron²,

Lefort³

et al. 2015

Cancer Prevention Research

103

106

View full text Add to dashboard Cite

Increases in serum levels of prostate-specific antigen (PSA) occur commonly in prostate cancer after radical prostatectomy and are designated "biochemical recurrence." Because the phytochemical sulforaphane has been studied extensively as an anticancer agent, we performed a double-blinded, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 AE 6 years) with increasing PSA levels after radical prostatectomy. Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months (M0-M6) followed by 2 months without treatment (M6-M8). The study was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6. The primary endpoint was not reached. For secondary endpoints, median log PSA slopes were consistently lower in sulforaphanetreated men. Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group (þ0.099 AE 0.341 ng/mL) than in placebo (þ0.620 AE 1.417 ng/mL; P ¼ 0.0433). PSA doubling time was 86% longer in the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively). PSA increases >20% at M6 were significantly greater in the placebo group (71.8%) than in the sulforaphane group (44.4%); P ¼ 0.0163. Compliance and tolerance were very good. Sulforaphane effects were prominent after 3 months of intervention (M3-M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms. Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy. Cancer Prev Res; 8(8); 712-9. Ó2015 AACR.

show abstract

“…It is responsible for DNA fragmentation and some of the distinct morphological features of apoptotic cells such as shrinkage and budding. 32 The results of light microscopy to determine cell morphology proved that apoptotic changes were independent of caspase-3, which is lacking in MCF-7 cells. From these results one can suggest that apoptosis induced by Euphorbia hirta leaves extract does not correlate with the activation of caspase-3 but may activate different apoptotic pathways and other effector caspases such as caspase-6 or -7.…”

Section: Acknowledgementmentioning

confidence: 97%

“…38 Or that some cell lines, such as MCF-7, can undergo apoptosis without showing DNA fragmentation due to lack of caspase-3 which is responsible for this feature. 32 Another explanation may be that the long incubation time of DNA led to lyses of a substantial part of the cell population. The smear pattern was also observed in the controls for both cell types that were treated with 0.1% DMSO for 72 h, which confirms the previous explanation.…”

Section: Acknowledgementmentioning

confidence: 99%

Apoptosis and Necrosis of Human Breast Cancer Cells by an Aqueous Extract of Euphorbia hirta leaves

Behera¹,

Dash²,

Pradhan³

et al. 2016

JYP

View full text Add to dashboard Cite

Introduction: Traditional medicines for mammary tumour are unreasonable and have genuine symptoms. Non-ordinary normal medications have increased wide acknowledgment because of their assurance of a cure with negligible or no symptoms, however minimal experimental confirmation exists. One such basic cure is the leaves of the Euphorbia hirta plant. Methods: It is initially reported utilization of the fluid concentrate of Euphorbia hirta leaves breast cancer cells. The capacity of the concentrate to impel apoptosis and corruption in the human bosom malignancy cell line MCF-7, contrasted with typical human skin fibroblasts (MDA MB-231), was dictated by morphological changes in the cells utilizing light microscopy, DNA fragmentation, and brilliant stains (Annexin V and Propidium Iodide) utilizing Flow Cytometry and fluorescent microscopy. Results: Apoptosis was instigated in both cells, and more in MCF-7, when they were treated with 25% and half concentrate, while rot was watched mostly after presentation to raised concentrate fixations (75%). DNA discontinuity came about for both cells, in a period and dosage subordinate way. Both cells, at all concentrate fixations, demonstrated no critical contrasts in the quantity of living, dead, apoptotic, and necrotic cells. Conclusion: At long last, the outcomes might show that apoptotic changes in MCF-7 might be free of caspase-3, which is included in apoptosis and is inadequate in MCF-7 cells.

show abstract

Safety, Tolerance, and Metabolism of Broccoli Sprout Glucosinolates and Isothiocyanates: A Clinical Phase I Study

Cited by 294 publications

References 20 publications

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain

Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy

Apoptosis and Necrosis of Human Breast Cancer Cells by an Aqueous Extract of Euphorbia hirta leaves

Contact Info

Product

Resources

About