Endotoxin Leakage and Toll-like Receptor 4 Up-regulation Promote Doxorubicin-caused Systemic Inflammation

Lintao Wang1, Qian Chen1, Haixia Qi1, Chunming Wang2, Cheng Wang1,3, Junfeng Zhang1,4,*, Lei Dong1,*

  1. State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
  2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR.
  3. Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road,Nanjing, 210002, China
  4. Jiangsu Provincial Laboratory for Nano-Technology, Nanjing University, Nanjing, P. R. China

* Corresponding author at: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin avenue, Nanjing 210093, China.

E-mail addresses: (J. Zhang), (L. Dong).

Catalogue

  1. Table S1…………………………………………………………………………...Page 3
  2. Supplementary Fig S1……………………………………………………………Page 4
  3. Supplementary Fig S2……………………………………………………….…..Page 5
  4. Supplementary Fig S3…………………………………………………….……..Page 6
  5. Supplementary Fig S4……………………………………………………….…..Page 7
  6. Supplementary Fig S5……………………………………………………….…..Page 8
  7. Supplementary Fig S6……………………………………………………….…..Page 9

Table S1: Information of the clinical sample donors.

Sample no. / Gender / Age / Disease / Previous Treatment
Health Donor
1 / Male / 45 / - / -
2 / Female / 47 / - / -
3 / Female / 51 / - / -
4 / Female / 58 / - / -
5 / Male / 60 / - / -
6 / Male / 52 / - / -
7 / Male / 47 / - / -
8 / Female / 50 / - / -
9 / Female / 59 / - / -
10 / Male / 62 / - / -
Cancer Patient Without DOX Treatment
1 / Male / 47 / Lymphoma / -
2 / Male / 64 / Lymphoma / -
3 / Male / 52 / Lymphoma / -
4 / Female / 53 / Lymphoma / -
5 / Male / 60 / Lymphoma / -
6 / Female / 59 / Lymphoma / -
7 / Female / 68 / Gastric Cancer / -
8 / Male / 69 / Gastric Cancer / -
9 / Male / 57 / Gastric Cancer / -
10 / Male / 58 / Gastric Cancer / -
Cancer Patient With DOX Treatment
1 / Female / 70 / Lymphoma / Doxorubicin
2 / Female / 63 / Lymphoma / Doxorubicin
3 / Male / 66 / Lymphoma / Doxorubicin
4 / Female / 45 / Lymphoma / Doxorubicin
5 / Male / 66 / Lymphoma / Doxorubicin
6 / Male / 61 / Lymphoma / Doxorubicin
7 / Female / 47 / Breast Cancer / Doxorubicin
8 / Female / 65 / Breast Cancer / Doxorubicin
9 / Female / 45 / Breast Cancer / Doxorubicin
10 / Female / 45 / Breast Cancer / Doxorubicin
11 / Female / 59 / Breast Cancer / Doxorubicin
12 / Female / 43 / Gastric Cancer / Doxorubicin
13 / Male / 55 / Gastric Cancer / Doxorubicin
14 / Male / 66 / Gastric Cancer / Doxorubicin

Supplementary Fig S1

Supplementary Fig S1. The ET concentration in DGM mice receiving DOX (20 mg/kg body weight) and/or LPS. (n=10). *p < 0.05.

Supplementary Fig S2

Supplementary Fig S2. Serum level of IL-1β in DGM mice receiving DOX (20 mg/kg body weight) and/or LPS (n=10). *p < 0.05.

Supplementary Fig S3

Supplementary Fig S3. Body weights of DGM mice receiving DOX (20 mg/kg body weight) and/or LPS. LPS at 5 mg/kg body weight killed all the animals at the 3rd day (n=10).

Supplementary Fig S4

Supplementary Fig S4. Evaluation of multi-organ damages in DGM+DOX+LPS group and in DGM+DOX group. (A) Serum levels of CK, LDH, BUN and ALT in DGM+DOX, DGM+DOX+2mg/kg LPS and DGM+DOX+5mg/kg LPS mice (n=10). *p < 0.05 versus DGM+DOX/DGM+DOX+2mg/kg LPS or DGM+DOX+5mg/kg LPS. (B) Representative histological images of H&E staining of the heart, kidney and liver of the experimental mice.

Supplementary Fig S5

Supplementary Fig S5. The influence of Rapamycin on the toxicity of DOX, as evidenced by the change in body weight (left panel) and the survival rate (right panel) of mice receiving DOX (20 mg/kg body weight). (n=10).

Supplementary Fig S6

Supplementary Fig S6. Multi-organ damages in DOX+Rapamycin group and DOX group. (A) Serum levels of CK, LDH, BUN and ALT in DOX and DOX+Rapamycin groups (n = 10). *p < 0.05. (B) Representative histological images of H&E staining of the heart, kidney, and liver.

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