The Safety and Fate of Potassium Sodium Copper Chlorophyllin and Other Copper Compounds*

Harrisson, Joseph W.E.; Levin, Simon E.; Trabin, Bernard

doi:10.1002/jps.3030431206

Cited by 35 publications

(29 citation statements)

References 11 publications

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“…Chlorophyll (Structure 1) and its derivatives have been shown to exert profound antimutagenic behavior against a wide range of potential human carcinogens 15, 16. Similarly, chlorophyllin (Structure 1), a food‐grade derivative of chlorophyll, has been used historically in the treatment of several human conditions, with no evidence of human toxicity 17, 18. Recently it was used as a potent inhibitor of aflatoxin B 1 hepatocarcinogenesis in rainbow trout 19.…”

Section: Introductionmentioning

confidence: 99%

Human serum albumin complexes with chlorophyll and chlorophyllin

2005

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Porphyrins and their metal derivatives are strong protein binders. Some of these compounds have been used for radiation sensitization therapy of cancer and are targeted to interact with cellular DNA and protein. The presence of several high-affinity binding sites on human serum albumin (HSA) makes it possible target for many organic and inorganic molecules. Chlorophyll a and chlorophyllin (a food-grade derivative of chlorophyll), the ubiquitous green plant pigment widely consumed by humans, are potent inhibitors of experimental carcinogenesis and interact with protein and DNA in many ways. This study was designed to examine the interaction of HSA with chlorophyll (Chl) and chlorophyllin (Chln) in aqueous solution at physiological conditions. Fourier transform infrared, UV-visible, and CD spectroscopic methods were used to determine the pigment binding mode, the binding constant, and the effects of porphyrin complexation on protein secondary structure. Spectroscopic results showed that chlorophyll and chlorophyllin are located along the polypeptide chains with no specific interaction. Stronger protein association was observed for Chl than for Chln, with overall binding constants of K(Chl) = 2.9 x 10(4)M(-1) and K(Chln) = 7.0 x 10(3)M(-1). The protein conformation was altered (infrared data) with reduction of alpha-helix from 55% (free HSA) to 41-40% and increase of beta-structure from 22% (free HSA) to 29-35% in the pigment-protein complexes. Using the CDSSTR program (CD data) also showed major reduction of alpha-helix from 66% (free HSA) to 58 and 55% upon complexation with Chl and Chln, respectively.

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Section: Introductionmentioning

confidence: 99%

Human serum albumin complexes with chlorophyll and chlorophyllin

2005

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“…In general, the EC 50 values in a cell based assay should be in the nanomolar range, which is true of most commercially available drugs. However, chlorophyllin sodium copper salt was reported to be safe even with extremely high doses of more than 1 gram/kg/day in rats 37 . Thus, this drug itself may exert pharmacological effects on Nrf2 signaling in vivo safely even with high dose administration.…”

Section: Discussionmentioning

confidence: 99%

Drug-Repositioning Screening for Keap1-Nrf2 Binding Inhibitors using Fluorescence Correlation Spectroscopy

Yoshizaki

Mori

Ishigami‐Yuasa

et al. 2017

Sci Rep

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The Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. The Cul3/Keap1 E3 ubiquitin ligase complex interacts with Nrf2, leading to Nrf2 ubiquitination and degradation. In this study, we focused on the disruption of the Keap1-Nrf2 interaction to upregulate Nrf2 expression and the transcription of ARE-controlled cytoprotective oxidative stress response enzymes, such as HO-1. We completed a drug-repositioning screening for inhibitors of Keap1-Nrf2 protein-protein interactions using a newly established fluorescence correlation spectroscopy (FCS) screening system. The binding reaction between Nrf2 and Keap1 was successfully detected with a KD of 2.6 μM using our FCS system. The initial screening of 1,633 drugs resulted in 12 candidate drugs. Among them, 2 drugs significantly increased Nrf2 protein levels in HepG2 cells. These two promising drugs also upregulated ARE gene promoter activity and increased HO-1 mRNA expression, which confirms their ability to dissociate Nrf2 and Keap1. Thus, drug-repositioning screening for Keap1-Nrf2 binding inhibitors using FCS enabled us to find two promising known drugs that can induce the activation of the Nrf2-ARE pathway.

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“…Previously, Harrison et al (1954) had reported neither copper-related toxic nor photosensitizing effects of Cu-Chl. Furthermore, the LD 50 of potassium sodium copper chlorophyllin was established as 190 μg gram − 1 body weight for mice.…”

Section: Antagonistic Effects and Lack Of Bioactivitymentioning

confidence: 99%

“…For instance, Harrison, Levin, and Trabin (1954) reported neither any kind of pathology or toxicity related to copper nor any photosensitization effects in a study of rats fed a diet supplemented with Cu-Chl. However, more recent studies have shown tumor-enhancing and genotoxic effects of the complex (Chernomorsky, Rancourt, Virdi, Segelman, & Poretz, 1997;Romert, Curvall, & Jenssen, 1992;Sarkar, Sharma, & Talukder, 1994).…”

Section: Introductionmentioning

confidence: 96%