sulfasalazine

Sulfasalazine is a drug for the treatment of rheumatoid arthritis and ulcerative colitis. Sulfasalazine is reported to suppress NF-κB activity.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> NF-κB >> NF-κB

Research Areas >> Inflammation/Immunology

RelA

Autophagy

Treatment of SW620 colon cells with sulfasalazine inhibits TNFα-, LPS-, or phorbol ester-induced NFκB activation. NFκB–dependent transcription is inhibited by sulfasalazine at micro- to millimolar concentrations. TNFα-induced nuclear translocation of NFκB is prevented by sulfasalazine through inhibition of IκBα degradation[1]. Pre‐incubation with 5 mM of sulfasalazine alone significantly increases basal mRNA expression of all pro‐inflammatory cytokines with levels of IL‐6 mRNA increased by 80‐fold compared with vehicle control[2]. Once digested, sulfasalazine is cleaved into sulfapyridine and 5-aminosalicylic acid by colonic bacteria, and the latter, too, is reported to suppress NF-kappaB activity[3].

At low doses (0.25 mM), SAS is able to suppress glioma growth by over 60% compared to untreated controls[3].

Sulfasalazine is dissolved in culture medium. SW620 cells are grown in Dulbecco’s modified Eagle medium, supplemented with 10% heat-inactivated FCS, 2 mmol/liter glutamine, and 1% (wt/vol) penicillin/streptomycin. SW620 cells are transfected with the 3xIgkBLuc reporter construct. After 18 h, cells are incubated with either medium alone or with sulfasalazine (0.1, 0.2, 0.5, 1, 2, 5 mM) before stimulation with TNFα, LPS, or PMA. Luciferase assay is performed[1].

Mice: Sulfasalazine is dissolved in 0.1 M NaOH, and then neutralized by titrating with 0.1 M HCl. U-87MG glioma cells are implanted into the cranium of a SCID mouse. After 7 days, animals are randomized into three groups of five animals each. One group receives 1 mL i.p. saline injections twice daily for 3 weeks. The two test groups receives 8 mg of sulfasalazine in 1 mL saline twice daily for 3 weeks. Tumor growth and animal health were monitored. After perfusion with 4% paraformaldehyde, mouse brains were collected, rinsed, and placed in 30% sucrose[3].

[1]. Wahl C, et al. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest. 1998 Mar 1;101(5):1163-74.

[2]. Sykes L, et al. Sulfasalazine augments a pro-inflammatory response in interleukin-1β-stimulated amniocytes and myocytes. Immunology. 2015 Dec;146(4):630-44.

[3]. Chung WJ, et al. Sulfasalazine inhibits the growth of primary brain tumors independent of nuclear factor-kappaB. J Neurochem. 2009 Jul;110(1):182-93.

BAY 11-7082 | Ammonium 1-pyrrolidinedithiocarbamate | SN50 | Triptolide | JSH-23 | Shikonine | Bay 11-7085 | Rocaglamide | (-)-DHMEQ | Dihydroartemisinin | Tomatidine | QNZ (EVP4593) | Baicalin | Laquinimod | Parthenolide

DATA ITEMS CITED :

38

MOLECULAR FORMULA :

C18-H14-N4-O5-S

MOLECULAR WEIGHT :

398.42

WISWESSER LINE NOTATION :

T6NJ BSWMR DNUNR DQ CVQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1286 mg/kg/30D-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes Blood - eosinophilia Blood - changes in cell count (unspecified)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

570 mg/kg/11D-I

TOXIC EFFECTS :

Blood - leukopenia Blood - thrombocytopenia Blood - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

3800 mg/kg/19D-I

TOXIC EFFECTS :

Liver - hepatitis (hepatocellular necrosis), diffuse

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

7143 ug/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

143 mg/kg/10D-I

TOXIC EFFECTS :

Blood - thrombocytopenia

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3200 mg/kg/31D-I

TOXIC EFFECTS :

Blood - agranulocytosis Blood - other changes Skin and Appendages - dermatitis, allergic (after systemic exposure)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

429 mg/kg/10D-I

TOXIC EFFECTS :

Blood - other hemolysis with or without anemia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

357 mg/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - headache

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

140 mg/kg/2W-I

TOXIC EFFECTS :

Behavioral - headache Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

1300 mg/kg/4W-I

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - ataxia Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

2700 mg/kg/13W-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure) Immunological Including Allergic - uncharacterized

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Rectal

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

7143 ug/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3870 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1520 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

12500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1096 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>7500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

32400 mg/kg/16D-I

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Endocrine - changes in thymus weight Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

32400 mg/kg/16D-I

TOXIC EFFECTS :

Gastrointestinal - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

177 mg/kg/2Y-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Kidney, Ureter, Bladder - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

141 mg/kg/2Y-I

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8100 mg/kg

SEX/DURATION :

female 1-40 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5460 mg/kg

SEX/DURATION :

male 13 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8400 mg/kg

SEX/DURATION :

male 28 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

16800 mg/kg

SEX/DURATION :

male 28 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

7 gm/kg

SEX/DURATION :

male 35 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8400 mg/kg

SEX/DURATION :

male 14 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

43875 mg/kg

SEX/DURATION :

male 13 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

MUTATION DATA

TEST SYSTEM :

Rodent - mouse

DOSE/DURATION :

5634 mg/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 283,53,1992 *** REVIEWS *** TOXICOLOGY REVIEW DPIRDU Dangerous Properties of Industrial Materials Report. (Van Nostrand Reinhold, 115 Fifth Ave., New York, NY 10003) V.1- 1981- Volume(issue)/page/year: 1(8),8,1981 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5355 No. of Facilities: 48 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 704 (estimated) No. of Female Employees: 435 (estimated)