Table 1.
Description of studies and outcomes reported for (a) troglitazone and (b) rosiglitazone.
| References | # animals/participants | Age | Strain/species | Sex | Drug dose | Route | Exposure time | ALT | AST | ALP | Total bilirubin | Liver weight, relative | Liver weight, absolute | Histo-pathology |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (a) Troglitazone studies | ||||||||||||||
| Studies in mice (n = 5) | ||||||||||||||
| Bedoucha 2001 | 3 mice/group | 13 weeks | C57BL/6 J | M | 0, 100 mg/kg/day | p.o. (gavage) | 28 days | X | ||||||
| Fujimoto 2009 |
10 mice/group 9 mice/group |
8 weeks 35 weeks |
Wild type Sod2 + / + | M | 0, 300 mg/kg/day | p.o. (gavage) | 28 days | X | X | X | X | X | X | X |
| Jia et al. 2019 | 4–6 mice/group | 6 weeks | BALB/c | F | 0, 30, 100, 300 mg/kg | i.p | 1 day/single dose | X | X | X | ||||
| Mak et al. 2018 |
3 mice/group 5 mice histopath control |
8–10 weeks | C57BL/6 | F | 0.2% w/w chow ad libitum | Diet | 5 weeks | X | X | |||||
| Ong et al. 2007 | 5 mice/group | 16–21 weeks | Wild type Sod2 + / + | M/F | 0, 30 mg/kg/day | i.p | 28 days | X | ||||||
| Studies in rats (n = 9) | ||||||||||||||
| Boitier 2011 | 5 rats/group | 8–10 weeks | Wistar | M | 0, 200, 1500 mg/kg/day | p.o. (gavage) | 14 days | X | ||||||
| Cepa et al. 2018 | 10 rats/sex/group | 88 to 94 days old | Sprague Dawley | M/F | 0, 25, 50 mg/kg | i.v | 1 day/single dose | X | X | X | ||||
| Cheng et al. 2017 | 4–5 rats/group | Not reported | Sprague Dawley | M | 0, 200 mg/kg/day | Oral gavage | 7 days/daily dose | X | X | X | ||||
| Hermann 2002 | 60 rats per sex per group (480 rats) | 7 weeks | Wistar | F | 0, 25, 50, 200 mg/kg/day | p.o. (gavage) | 104 weeks | X | ||||||
| M | 0, 100, 400, 800 mg/kg/day | |||||||||||||
| Jia 2000 | 6–10 rats/group | 12 weeks | Long-Evans Tokushima Otsuka (LETO) | M | 0, 200 mg/100 g food | p.o.(diet) | 60 weeks (until 72 wks old) | X | X | X | X | X | ||
| 28 weeks | M | 0, 200 mg/100 g food | 44 weeks (until 72 wks old) | |||||||||||
| Kakiuchi-Kiyota 2011 | 10 rats/group | 7 weeks | Wistar | F | 0, 50, 200 mg/kg/day | p.o. (gavage) | 4 weeks | X | X | |||||
| Kostrubsky 2001 | 4 rats/group | Not reported | Wistar | M | 0, 200 mg/kg | p.o. (gavage) | 2 h 36 h | X | ||||||
| Li 2002 | 5 rats/group | 10 weeks | Wistar/ST | M | 0,100, 500 mg/kg/day | p.o. (diet) | 3 weeks | X | X | |||||
| Watanabe 2000 | 5 rats/sex/group | 7 weeks | Wistar | M/F | 0, 100, 400 mg/kg | p.o. (gavage) | 94 days | X | X | X | X | |||
| Study in NHP (non-human primates; n = 1) | ||||||||||||||
| Rothwell 2002 | 4 NHP/sex/group | 2 to 6 years | Cynomolgus Macaques | M/F | 0, 300, 600, 1200 mg/kg | p.o. (gavage) | 52 weeks | X | X | X | X | X | X | X |
| Studies in humans (n = 7) | ||||||||||||||
| Arioglu 2000 | 20 patients | 6 to 65 years | – | M/F | 200 to 600 mg/day | p.o | 6 months | X | X | |||||
| Azziz 2001 | 305 patients | 30.1 + /- 6.0 years | – | F | Placebo | p.o | 44 weeks | X | X | |||||
| 28.9 + /- 5.4 years | 150 mg/day | |||||||||||||
| 29.2 + /- 5.8 years | 300 mg/day | |||||||||||||
| 29.0 ± 5.2 years (mean + /- SD) | 600 mg/day | |||||||||||||
| Björnsson 2006* | 148 cases | Not reported | – | - | Not reported | p.o | Not reported | |||||||
| Knowler 2005 | 582 + 585 patients | 51 years (mean) | – | M/F | Placebo, 400 mg/day | p.o | 0.9 year (mean) (range 0.5 to 1.5 years) | X | X | |||||
| Mavandadi 1999 | 21 patients | 31–64 years | – | M/F | 200 to 600 mg/day | p.o | 6 months | X | X | |||||
| St.Peter 2001 | 291 patients | 53.5 ± 12.8 (mean + /- SD) | – | M/F | Not reported | p.o | 412.7 ± 255.6 days (mean + /- SD) | X | X | |||||
| Yale 2001 | 200 patients | 59 years (mean) | – | M/F | 400 mg/day | p.o | 6–12 months | X | ||||||
| References | # animals/participants | Age | Strain/species | Sex | Drug dose | Route | Exposure time | ALT | AST | ALP | Total bilirubin | Liver weight, relative | Liver weight, absolute | Histo-pathology |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (b) Rosiglitazone studies | ||||||||||||||
| Studies in mice (n = 5) | ||||||||||||||
| Anandharajan 2009 | 8 mice/group | 7–9 weeks | C57BL/6 J | M | 0, 10 mg/kg/day | p.o. (gavage) | 10 days | X | X | X | ||||
| Bedoucha 2001 | 3 mice/group | 13 weeks | C57BL/6 J | M | 0, 2.5 mg/kg/day | p.o. (gavage) | 28 days | X | ||||||
| Jia et al. 2019 | 4–6 mice/group | 6 weeks | BALB/c | F | 0, 30, 100, 300 mg/kg | i.p | 1 day/single dose | X | X | X | ||||
| Otake 2011 | 5 mice/group | 7 weeks | ICR | M | 0, 30,100 mg/kg/day | p.o. (gavage) | 14 days | X | ||||||
| Zhang et al. 2019 | 6 mice/group | 8 weeks | C57BL/6 J | M | 0, 30 mg/kg/day | Gastric intubation | 6 days | X | X | X | X | X | X | X |
| Studies in rats (n = 7) | ||||||||||||||
| Anandharajan 2009 | 8 rats/group | 6 weeks | Wistar | F | 0, 40 mg/kg/day | p.o. (gavage) | 28 days | X | X | X | ||||
| Anwar et al. 2015 | 6 rats/group | 7–8 weeks | Sprague–Dawley | M/F | 0, 40 mg/kg/day | Diet | 16 weeks | X | X | X | X | X | ||
| Dadarkar 2011 | 3 rats/group | 8 weeks | Sprague Dawley | F | 0, 300 mg/kg | i.p | 1 day/single dose | X | X | X | X | X | ||
| Egerod 2009 |
10 rats 5 rats 5 rats |
6 weeks | Sprague Dawley | M |
0 mg/kg/day 8 mg/kg/day 20 mg/kg/day |
p.o. (gavage) | 7 days | X | X | |||||
| Meghani 2012 | 6 rats/group | Not reported | Wistar | M | 0, 80 mg/kg/day | p.o.(gavage) | 14 days | X | X | X | X | |||
| Schafer et al. 2012 | 6 rats | 10 weeks | ZDF | M | 3 mg/kg | p.o. (gavage) | 8 weeks | x | X | X | ||||
| Spicker et al. 2007 |
9 rats 5 rats |
5–6 weeks | Sprague Dawley | M |
0, 1000 mg/kg/day |
p.o. (gavage) | 1 day/single dose | X | X | |||||
| Studies in humans (n = 11) | ||||||||||||||
| Aramwit 2009 | 13 patients | 54.17 ± 11.42 years (Mean + /- SD. Range 35–85 years) | – | M/F | 4 mg/day | p.o | 12 weeks | X | X | |||||
| Beysen 2008 | 6 patients | 56 + /- 6 years (Mean + /- SD) | – | M/F | 16 mg/day for 4 weeks followed by 8 mg/day for 16 weeks | p.o | 20 weeks | X | X | |||||
| Chalasani 2005 | 210 patients (Cohort 1) | 53 ± 11 years | – | M/F | 4.4 + /- 1.8 mg/day | p.o | 12 months | X | X | X | ||||
| 628 patients (Cohort 2) | 55 + /- 11 years (Mean + /- SD) | 4.4 + /- 2 mg/day (mean + /- SD) | ||||||||||||
| Chiang 2007 | 78 patients | 56.8 + /- 7.2 years (Mean + /- SD) | – | M/F | 2 to 8 mg/day | p.o | 3–12 months | X | X | X | ||||
| Dereli 2005 | 20 patients | 29.4 ± 1.7 years | – | F | 2 mg/day | p.o | 8 months | X | X | |||||
| 20 patients | 31.4 ± 0.9 years (Mean + /- SD) | 4 mg/day | ||||||||||||
| Gegick 2001* | 77 patients | 59 ± 10.4 | – | M/F | 4 or 8 mg/day | p.o | 3.2 months | |||||||
| Gegick 2004* | 49 patients | 59.5 ± 10.9 (Mean + /- SD) | – | M/F | 4 or 8 mg/day | p.o | 12.6 months | |||||||
| Hussein 2004 | 96 patients | 64.6 + /- 10.3 Mean + /- SD. Range 41–82 years) | _ | M/F | 4 or 8 mg/day | p.o. | 2 months | X | ||||||
| Nolan 2000 | 93 patients | 62.3 + /- 9.5 (Mean = /- SD. Range 39–80 years) | – | M/F | Placebo, | p.o | 8 weeks | X | ||||||
| 95 patients | 62.9 ± 10.1 (Mean = /- SD. Range 43–83 years | 4 mg/day | ||||||||||||
| 90 patients | 62.6 ± 9.9 years (Mean + /- SD. Range 40–80 years) | 8 mg/day | ||||||||||||
| 91 patients | 63.4 + /- 9.1 (Mean + /- SD. Range 41–79 years) | 12 mg/day | ||||||||||||
| Phillips 2001 | 173 patients | 57.7 ± 9.2 years | – | M/F | Placebo, | p.o | 26 weeks | X | ||||||
| 181 patients | 57.5 ± 9.9 years | 4 mg o.d | ||||||||||||
| 186 patients | 56.8 ± 9.4 years | 2 mg b.i.d | ||||||||||||
| 181 patients | 58.9 ± 9.9 years | 8 mg o.d | ||||||||||||
| 187 patients | 56.5 ± 9.7 years (Mean + /- SD) | 4 mg b.i.d | ||||||||||||
| Wong 2005* | 52 patients | 62.92 ± 7.30 rosiglitazone and 61.58 ± 9.7 control | – | M/F | 4 mg/day | p.o | 24 weeks | |||||||
*Narrative review includes no numerical data.