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Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Research article

A 13-Week Repeated Oral Dose Toxicity Study of ChondroT in Sprague-Dawley Rats

Authors: Jiwon Jeong, Kiljoon Bae, Jihoon Kim, Chanhun Choi, Changsu Na, Myeongkyu Park, Youngran Kim, Chang-Seob Seo, Seon-Jong Kim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

ChondroT, a new herbal medication, consists of Angelica grosseserrata Maxim., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis terniflora var. manshurica (Rupr.) Ohwi, and Phellodendron amurense Rupr. (6:4:4:4:3). Our previous studies have shown that ChondroT exhibits significant anti-arthritic and anti-inflammatory effects. In this study, we aimed to assess the toxicological safety assessment of ChondroT.

Methods

This study was designed to assess the safety of ChondroT after repeated oral administration.
Male and female Sprague-Dawley rats were treated with ChondroT at oral doses of 0, 500, 1000, and 2000 mg/kg for 13 weeks. Mortality, clinical signs, body weight changes, food consumption, ophthalmological findings, urinalysis, hematological and blood-chemical parameters, necropsy findings, organ weights, and histological markers were recorded throughout the study period. Rats were also monitored for an additional 4 weeks to determine the recovery time.

Results

No death occurred and no significant changes in food consumption, ophthalmologic findings, and urinalysis were found. Although there were alterations in clinical signs, body weights, hematological parameters, blood-chemical parameters, necropsy findings, organ weights, and histological markers, they were not considered to be toxicologically significant.

Conclusions

The results suggest that the no-observed adverse effects level (NOAEL) was 2000 mg/kg/day for the test substance. ChondroT, a new complex herbal medication composed of five plants, can therefore be used safely at the NOAEL.
Literature
1.
go back to reference Kim YH, Lee JH. CheongKangEuiGam. Seoul: Seongbosa; 2001. p. 315. Kim YH, Lee JH. CheongKangEuiGam. Seoul: Seongbosa; 2001. p. 315.
2.
go back to reference Jeoung BR, Lee KD, Na CS, Kim YE, Kim B, Kim YR. Ganghwaljetongyeum, an anti-arthritic remedy, attenuates synoviocyte proliferation and reduces the production of proinflammatory mediators in macrophages: the therapeutic effect of GHJTY on rheumatoid arthritis. BMC Complement Altern Med. 2013;13:47–52.CrossRef Jeoung BR, Lee KD, Na CS, Kim YE, Kim B, Kim YR. Ganghwaljetongyeum, an anti-arthritic remedy, attenuates synoviocyte proliferation and reduces the production of proinflammatory mediators in macrophages: the therapeutic effect of GHJTY on rheumatoid arthritis. BMC Complement Altern Med. 2013;13:47–52.CrossRef
4.
go back to reference Kim W, Park S, Choi C, Kim YR, Park I, Seo C, et al. Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats. Evid Based Complement Alternat Med. 2016;2016:1–10. Kim W, Park S, Choi C, Kim YR, Park I, Seo C, et al. Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats. Evid Based Complement Alternat Med. 2016;2016:1–10.
5.
go back to reference Bae KJ, Jeong JW, Choi CH, Won JY, Kim TG, Kim YR, et al. Antiosteoarthritic Effects of ChondroT in a Rat Model of Monosodium Iodoacetate-Induced Osteoarthritis. Evid Based Complement Alternat Med. 2018;2018:1–11.CrossRef Bae KJ, Jeong JW, Choi CH, Won JY, Kim TG, Kim YR, et al. Antiosteoarthritic Effects of ChondroT in a Rat Model of Monosodium Iodoacetate-Induced Osteoarthritis. Evid Based Complement Alternat Med. 2018;2018:1–11.CrossRef
6.
go back to reference Jeong JW, Bae KJ, Kim SG, Kwak DW, Moon Y-J, Choi CH, et al. Anti-osteoarthritic effects of ChondroT in a rat model of collagenase-induced osteoarthritis. BMC Complement Altern Med. 2018;18:131–40.CrossRef Jeong JW, Bae KJ, Kim SG, Kwak DW, Moon Y-J, Choi CH, et al. Anti-osteoarthritic effects of ChondroT in a rat model of collagenase-induced osteoarthritis. BMC Complement Altern Med. 2018;18:131–40.CrossRef
7.
go back to reference Park JU, Kim SJ, Na CS, Choi C, Seo CS, Son JK, et al. Chondroprotective and anti-inflammatory effects of ChondroT, a new complex herbal medication. BMC Complement Altern Med. 2016;16:213–23.CrossRef Park JU, Kim SJ, Na CS, Choi C, Seo CS, Son JK, et al. Chondroprotective and anti-inflammatory effects of ChondroT, a new complex herbal medication. BMC Complement Altern Med. 2016;16:213–23.CrossRef
8.
go back to reference Oh DR, Kim JR, Choi CY, Choi C hun, Na C su, Kang BY, et al. Effects of ChondroT on potassium Oxonate-induced Hyperuricemic mice: downregulation of xanthine oxidase and urate transporter 1. BMC Complement Altern Med. 2019;19:10–17. Oh DR, Kim JR, Choi CY, Choi C hun, Na C su, Kang BY, et al. Effects of ChondroT on potassium Oxonate-induced Hyperuricemic mice: downregulation of xanthine oxidase and urate transporter 1. BMC Complement Altern Med. 2019;19:10–17.
9.
go back to reference Lee S, Kim SJ. Efficacy and safety of ChondroT on knee-osteoarthritis: Protocol for a 8-week, randomized, double-blind, placebo-controlled, multicenter therapeutic exploratory clinical trial. Medicine Baltimore. 2018;97:e0170.CrossRef Lee S, Kim SJ. Efficacy and safety of ChondroT on knee-osteoarthritis: Protocol for a 8-week, randomized, double-blind, placebo-controlled, multicenter therapeutic exploratory clinical trial. Medicine Baltimore. 2018;97:e0170.CrossRef
10.
go back to reference Lim YH, Jeong JW, Kim SG, Kim JH, Kim SJ. DRF and Single Dose Oral Toxicity Study of ChondroT in Rat. J Korean Med Rehabil. 2018;28:61–72.CrossRef Lim YH, Jeong JW, Kim SG, Kim JH, Kim SJ. DRF and Single Dose Oral Toxicity Study of ChondroT in Rat. J Korean Med Rehabil. 2018;28:61–72.CrossRef
11.
go back to reference Dequeker J, Luyten FP. The history of osteoarthritis-osteoarthrosis. Ann Rheum Dis. 2008;67:5–10.CrossRef Dequeker J, Luyten FP. The history of osteoarthritis-osteoarthrosis. Ann Rheum Dis. 2008;67:5–10.CrossRef
12.
go back to reference Neogi T. Clinical significance of bone changes in osteoarthritis. Ther Adv Musculoskel Dis. 2012;4:259–67.CrossRef Neogi T. Clinical significance of bone changes in osteoarthritis. Ther Adv Musculoskel Dis. 2012;4:259–67.CrossRef
13.
go back to reference Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64:1539–41.CrossRef Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64:1539–41.CrossRef
14.
go back to reference Altman RD. Criteria for classification of clinical osteoarthritis. J Rheumatol Suppl. 1991;27:10–2.PubMed Altman RD. Criteria for classification of clinical osteoarthritis. J Rheumatol Suppl. 1991;27:10–2.PubMed
15.
go back to reference Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115–26.CrossRef Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377:2115–26.CrossRef
16.
go back to reference Zhang W, Doherty M, Peat G, Bierma-Zeinstra MA, Arden NK, Bresnihan B, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2010;69:483–9.CrossRef Zhang W, Doherty M, Peat G, Bierma-Zeinstra MA, Arden NK, Bresnihan B, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2010;69:483–9.CrossRef
17.
go back to reference Santos SR, Rangel ET, Lima JCS, Silva RM, Lopes L, Noldin VF, et al. Toxicological and phytochemical studies of Aspidosperma subincanum Mart. stem bark Guatambu. Pharmazie. 2009;64:836–9.PubMed Santos SR, Rangel ET, Lima JCS, Silva RM, Lopes L, Noldin VF, et al. Toxicological and phytochemical studies of Aspidosperma subincanum Mart. stem bark Guatambu. Pharmazie. 2009;64:836–9.PubMed
18.
go back to reference Son HY, Kim YB, Ha CS, Kang BH. Histopathological observation of spontaneous testicular atrophy in Sprague-Dawley rat. Korean J Vet Pathol. 1998;2:47–51. Son HY, Kim YB, Ha CS, Kang BH. Histopathological observation of spontaneous testicular atrophy in Sprague-Dawley rat. Korean J Vet Pathol. 1998;2:47–51.
19.
go back to reference Boorman GA. Pathology of the Fischer rat: reference and atlas. San Diego: Academic Press; 1990. Boorman GA. Pathology of the Fischer rat: reference and atlas. San Diego: Academic Press; 1990.
20.
go back to reference Pritam SS, James AP, Jerry FH, Chirukandath G. Toxicologic Pathology: Nonclinical Safety Assessment. Boca Raton: CRC Press; 2013. p. 77–96. Pritam SS, James AP, Jerry FH, Chirukandath G. Toxicologic Pathology: Nonclinical Safety Assessment. Boca Raton: CRC Press; 2013. p. 77–96.
21.
go back to reference Lee HY, Na YR, Seok SH, Baek MW, Kim DJ, Park SH, et al. Spontaneous Basal Cell Carcinoma in a 7-Week-Old Sprague-Dawley Rat. Vet Pathol. 2010;47:137–9.CrossRef Lee HY, Na YR, Seok SH, Baek MW, Kim DJ, Park SH, et al. Spontaneous Basal Cell Carcinoma in a 7-Week-Old Sprague-Dawley Rat. Vet Pathol. 2010;47:137–9.CrossRef
22.
go back to reference Zwicker GM, Eyster RC, Sells DM, Gass JH. Spontaneous Skin Neoplasms in Aged Sprague-Dawley Rats. Toxicol Pathol. 1992;20:327–40.CrossRef Zwicker GM, Eyster RC, Sells DM, Gass JH. Spontaneous Skin Neoplasms in Aged Sprague-Dawley Rats. Toxicol Pathol. 1992;20:327–40.CrossRef
23.
go back to reference Shannon RS, Minakshi N, Nihal A. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–61.CrossRef Shannon RS, Minakshi N, Nihal A. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–61.CrossRef
24.
go back to reference Choi J, Ryu SJ, Kim KJ, Kim HM, Chung HC, Lee BY. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats. Molecules. 2018;23:217–35.CrossRef Choi J, Ryu SJ, Kim KJ, Kim HM, Chung HC, Lee BY. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats. Molecules. 2018;23:217–35.CrossRef
Metadata
Title
A 13-Week Repeated Oral Dose Toxicity Study of ChondroT in Sprague-Dawley Rats
Authors
Jiwon Jeong
Kiljoon Bae
Jihoon Kim
Chanhun Choi
Changsu Na
Myeongkyu Park
Youngran Kim
Chang-Seob Seo
Seon-Jong Kim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2773-4

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