Pigmentation of kidneys and lymph nodes of mesocolon in rats fed diets containing the laxative danthron

Sjöberg, Per J. R.; Hedelin, U.; Kronevi, Tony; Lydén-Sokolowski, A.; Magnusson, Göran; Montin, G.; Olofsson, I.-M.; Lindquist, Nils Gunnar

doi:10.1016/0378-4274(88)90169-5

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…The severe sinus dilatation and increased yellow‐brown pigmentation in ileocecal lymph nodes observed here and in the previous 1‐y chronic toxicity study (Matsuda and others 2007) might be due to the inclusion of large amounts of anthraquinone in Aloe. In male Sprague–Dawley rats, the anthraquinone laxative danthron was reported to cause dilatation of the sinusoidal spaces and yellowish pigmentation in lymph nodes of the mesocolon (Sjoberg and others 1988) and, in human cases, anthraquinone laxatives cause melanosis coli and colorectal cancer (Nascimbeni and others 2002; Willems and others 2003). The yellowish pigmentation of kidneys also appeared similar to that in the ileocecal lymph nodes and again has been described earlier and considered as PAS‐positive and drug‐derived (Sjoberg and others 1988).…”

Section: Discussionmentioning

confidence: 99%

“…In male Sprague–Dawley rats, the anthraquinone laxative danthron was reported to cause dilatation of the sinusoidal spaces and yellowish pigmentation in lymph nodes of the mesocolon (Sjoberg and others 1988) and, in human cases, anthraquinone laxatives cause melanosis coli and colorectal cancer (Nascimbeni and others 2002; Willems and others 2003). The yellowish pigmentation of kidneys also appeared similar to that in the ileocecal lymph nodes and again has been described earlier and considered as PAS‐positive and drug‐derived (Sjoberg and others 1988). Although histopathologically diagnosed chronic nephropathy of the kidneys was also seen in both male and female groups in our study, there was no dose‐relation and similar lesions were found in the control group.…”

Section: Discussionmentioning

confidence: 99%

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Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High‐Dose Level in a Wistar Hannover Rat 2‐y Study

Yokohira¹,

Matsuda²,

Suzuki³

et al. 2009

Journal of Food Science

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A 2-y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high-dose level on colon in the 2-y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic-dose levels and that carcinogenic potential in at 4% high-dose level on colon is probably due to irritation of the intestinal tract by diarrhea.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High‐Dose Level in a Wistar Hannover Rat 2‐y Study

Yokohira¹,

Matsuda²,

Suzuki³

et al. 2009

Journal of Food Science

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One-year chronic toxicity study of Aloe arborescens Miller var. natalensis Berger in Wistar Hannover rats. A pilot study

Matsuda

Yokohira

Suzuki

et al. 2008

Food and Chemical Toxicology

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Identification of danthron as an isoform-specific inhibitor of HEME OXYGENASE-1/cytochrome P450 reductase interaction with anti-tumor activity

Chou

Hsu

et al. 2018

J Biomed Sci

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BackgroundHeme oxygenase (HO) catalyzes NADPH-dependent degradation of heme to liberate iron, carbon monoxide and biliverdin. The interaction between HO and cytochrome P450 reductase (CPR), an electron donor, is essential for HO activity. HO-1 is a stress-inducible isoform whereas HO-2 is constitutively expressed. HO-1 induction is commonly seen in cancers and impacts disease progression, supporting the possibility of targeting HO-1 for cancer therapy.MethodsWe employed a cell-based bioluminescence resonance energy transfer assay to screen compounds with ability to inhibit HO-1/CPR interaction. The effect of the identified compound on HO-1/CPR interaction was confirmed by pull down assay. Moreover, the anti-tumorigenic activity of the identified compound on HO-1-enhanced tumor growth and migration was assessed by trypan blue exclusion method and wound healing assay.ResultsDanthron was identified as an effective small molecule able to interfere with the interaction between HO-1 and CPR but not HO-2 and CPR. Additional experiments with structural analogues of danthron revealed that the positions of hydroxyl moieties significantly affected the potency of inhibition on HO-1/CPR interaction. Pull-down assay confirmed that danthron inhibited the interaction of CPR with HO-1 but not HO-2. Danthron suppressed growth and migration of HeLa cells with stable HO-1 overexpression but not mock cells. In contrast, anthrarufin, a structural analog with no ability to interfere HO-1/CPR interaction, exhibited no significant effect on HO-1-overexpressing HeLa cells.ConclusionsThese findings demonstrate that danthron is an isoform-specific inhibitor for HO-1/CPR interaction and may serve as a lead compound for novel anticancer drug.

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Pigmentation of kidneys and lymph nodes of mesocolon in rats fed diets containing the laxative danthron

Cited by 3 publications

References 10 publications

Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High‐Dose Level in a Wistar Hannover Rat 2‐y Study

Equivocal Colonic Carcinogenicity of Aloe arborescens Miller var. natalensis Berger at High‐Dose Level in a Wistar Hannover Rat 2‐y Study

One-year chronic toxicity study of Aloe arborescens Miller var. natalensis Berger in Wistar Hannover rats. A pilot study

Identification of danthron as an isoform-specific inhibitor of HEME OXYGENASE-1/cytochrome P450 reductase interaction with anti-tumor activity

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