Table 2.
Summary of CYP1A1 inhibitors tested in rodents and their major outcomes
| Drug | Disease | Study design |
Animal Model Sex; strain; age |
Drug administration Route; dose; duration |
Study outcomes | Ref |
|---|---|---|---|---|---|---|
|
Alizarin IC50 = 6.2 × 10−6 M |
Hepatotoxicity induced by bromobenzene | P | M; Kunming mice | PO; 5 mM/animal; single dose | ↓ hepatic lipid peroxidation and serum ALT | [127] |
| Mutagenesis induced by MeIQx | P | M; C57BL/6 N mice; 5 wo | PO (diet); 30 mg/animal; 3 or 6 d | Unchanged CYP1A1 (EROD assay); antimutagenic effect (↓ MeIQx-DNA adducts) | [128] | |
| Diabetes induced by alloxan | R | M; Kunming mice | 24, 48 or 96 mg/kg; 10 d | ↓ fasting blood glucose (dose-dependent) | [129] | |
|
Ellipticine IC50 = 1.1 × 10−7 M |
Lung cancer—xenograft model (A549 cells) | R | Balb/c nude mice; 5 wo | IP; 11.25 mg/kg; 14 d | ↓ tumor size | [134] |
| Septic shock model induced by lipopolysaccharide | P | F; C57BL/6 mice; 8–12 wo | IP; 10 or 20 mg/kg; single dose | ↓ TNF-α and IL-6 (time-dependent) in serum | [135] | |
|
Pterostilbene IC50 = 3.6 × 10−6 M |
Inflammation induced by carrageenan | P | M; C57Bl/6 mice | IP; 30 mg/kg; single dose | ↓ paw edema; ↓ IL-6 and MCP-1 protein in the paw tissue | [138] |
|
Purpurin IC50 = 5.5 × 10−6 M |
Mutagenesis induced by MelQx | P | M; C57BL/6 N mice; 5 wo | PO (diet); 30 mg/animal; 3 or 6 d | ↓ CYP1A1 activity (EROD assay); ↓ adduct formation in lungs and kidney and marginally in liver | [128] |
| Obesity induced by HFD | P | M; C57BL/6 mice; 6–8 wo | PO (diet); 40 or 80 mg/kg;10 w | ↓ in weight gain (dose-dependent) | [139] | |
|
Rhapontigenin IC50 = 4 × 10−4 M |
Myocardial infarction related to isoproterenol | P | M; SD rats | IV; 1, 2.5 or 5 mg/kg/day; OD, 8 d | ↓ infarct size, heart/body weight index, CK, LD and CTT; ↓ TNF-α, IL-6, MD, SOD, p38 and iNOS protein (5 mg/kg/day) in serum and heart tissue | [145] |
| Rutaecarpine | Myocardial infarction—coronary artery occlusion | P | M; Wistar rats | IV; 100 or 300 μg/kg; single dose | ↓ infarct size and creatine kinase activity; ↑ plasma CGRP (dose-dependent) | [153] |
| Systemic Hypertension—2 kidneys-1 clip | R | M; SD rats | PO; 10, 20 or 40 mg/kg; bid, 4 w | ↓ SBP and mesenteric arteries AngII content (dose-dependent); ↑ plasma CGRP and α- and β-CGRP mRNA (20 and 40 mg/kg) | [155] | |
| Systemic Hypertension—SHR | P | M; SHR and WKY rats; 16 wo | PO; 10, 20 or 40 mg/kg; bid, 18 d | ↓ SBP and platelet aggregation (20 and 40 mg/kg); ↑plasma CGRP and α- and β-CGRP mRNA (20 and 40 mg/kg) | [156] | |
| P | M; SHR and WKY rats; 16 wo | PO; 20 or 40 mg/kg/day; bid, 18 d | ↓ SBP and CK activity (dose-dependent); ↑plasma CGRP; improved vasorelaxation to Ach in aortic rings (ex vivo) | [157] | ||
| P | M; SHR and WKY rats 16 wo | PO; 10, 20 or 40 mg/kg/day; bid, 14 d | ↓ SBP (dose-dependent); ↑ plasma CGRP and α-CGRP mRNA; ↑ telomerase activity and ↓ EPC senescence | [158] | ||
| Atherosclerosis—HFD | P | F; C57Bl/6 ApoE−/− mice; 8 wo | PO; 10, 20 or 40 mg/kg; daily, 8 w | ↓ face lesions on the aorta (dose-dependent); ↓ TC and TG; ↑ ABCA1 and SR-BI protein and mRNA | [159] | |
| Right ventricular remodeling—Hypoxia | P | M; SD rats; 6–8 wo | PO; 20 or 40 mg/kg; OD, for 3 w | ↓ ventricular SBP (dose-dependent); ↓ cardiac ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a and TGF-β1 mRNA; ↓ TGF-β1 and ↑ CGRP in plasma | [154] | |
| Obesity—HFD + streptozotocin | R | M; SD rats | PO; 25 mg/kg; OD, 7 w | ↓ TC, TG, LDL-C, blood glucose; ↓ serum CRP, MCP-1, TNF-α and IL-6; ↓ liver NF-kB protein; ↑ HDL-C and insulin sensitivity | [161] | |
| Renal Injury—ischemia- reperfusion injury | P | M; SD rats; 6–8 wo | IP; 30 or 60 mg/kg; single dose | ↓ serum Cr, BUN, NGAL (dose-dependent); ↓ NF-kB, TNF-α, IL-6, ICAM-1 mRNA and protein; ↓ MD and ↑ SOD content in renal tissue | [162] | |
| Vascular disease—carotid balloon-injury | R | M; SD rats | PO; 25, 50 or 75 mg/kg; OD, 14 d | ↑ NO protein and eNOS mRNA (dose-dependent); ↑ plasma cGMP (highest dose); ↓ c-myc, ERK2 and PCNA mRNA (50 and 75 mg/kg); ↑ MKP-1 (highest dose) and p-ERK2 (50 and 75 mg/kg) protein | [160] |
-/-: null; α-SMA: α-smooth muscle actin; ABCA1: ATP binding cassette transporter A1; ACh: acetylcholine; ALT: alanine aminotransferase; AngII: angiotensin II; ANP: atrial natriuretic peptide; Bid: twice a day; BNP: B-type natriuretic peptide; BUN: blood urea nitrogen; cGMP: cyclic guanosine 3',5'-monophosphate; CGRP: calcitonin gene-related peptide; CK: creatinine kinase; Cr: creatinine; CRP: C-reactive protein; CTT: cardiac troponin-T; CYP1A1: cytochrome P450, family 1, subfamily A, polypeptide 1; d: days; eNOS: endothelial nitric oxide synthase; EPC: endothelial progenitor cell; ERK2: extracellular signal-regulated kinase 2; EROD: ethoxyresorufin-O-deethylase; F: Female; HDL-C: high density lipoprotein-cholesterol; HFD: high-fat diet; ICAM-1: intercellular adhesion molecule-1; IL: interleukin; iNOS: inducible nitric oxide synthase; IP: intraperitoneal; IV: intravenous; LD: lactate dehydrogenase; LDL-C: low density lipoprotein-cholesterol; M: Male; MeIQx: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; MCP-1: monocyte chemotactic protein-1; MD: malondialdehyde; MKP-1: MAPK phosphatase-1; NF-kB: nuclear factor kappa B; NGAL: neutrophil gelatinase-associated lipocalin; NO: nitric oxide; OD: once a day; P: prevention; PCNA: proliferating cell nuclear antigen; PO: Per os; R: reversion; SBP: systolic blood pressure; SD: Sprague–Dawley; SHR: spontaneously hypertensive rats; SOD: superoxide dismutase; SR-BI: scavenger receptor class B type I; TC: total cholesterol; TG: triglycerides; TGF-β1: transforming growth factor beta 1; TNF-α: tumor necrosis factor-α; w: weeks; wo: weeks old; WKY: Wistar Kyoto