Effects of the PPAR𝛼 Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism

Table 6

Hepatic peroxisomal enzyme activities in male special study Harlan Sprague Dawley rats, B6C3F1 mice, and Syrian hamsters following exposure to gemfibrozil in feed for 6 days, 34 days, or 13 weeks^a,b.

Rats	0 ppm	10 ppm	100 ppm	1000 ppm	8000 ppm	16000 ppm
Acyl CoA oxidase (nmol DCF/minute per mg)
Day 6	1.5±0.2	1.8±0.7	1.3±0.2	2.0±0.1	6.9±0.7^∗∗	11.1±1.0^∗∗
Day 34	1.8±0.2	1.9±0.1	2.5±0.5	5.2±0.4^∗∗	16.5±2.6^∗∗	22.1±2.4^∗∗
Week 13	1.6±0.1	1.6±0.1	2.9±0.4^∗	6.8±0.5^∗∗	27.2±0.9^∗∗	33.2±1.2^∗∗
𝛽-Oxidation(Lazarowmethod)(nmolNADH/minutepermg)
Day 6	1.0±0.1	1.0±0.1	1.0±0.2	2.3±0.3	12.2±1.0^∗∗	19.8±2.0^∗∗
Day 34	1.2±0.2	1.0±0.1	2.3±0.3^∗	10.0±1.3^∗∗	37.9±6.0^∗∗	55.8±7.0^∗∗
Week 13	1.4±0.2	1.4±0.1	2.4±0.3^∗	16.9±1.3^∗∗	75.2±4.8^∗∗	89.9±4.2^∗∗
Carnitineacetyltransferase(nmolreducedCoA/minutepermg)
Day 6	0.8±0.1	0.9±0.1	1.5±0.5^∗∗	2.0±0.1^∗∗	11.3±1.2^∗∗	15.9±1.7^∗∗
Day 34	0.7±0.1	0.7±0.1^c	2.3±0.2^∗∗	7.0±1.3^∗∗	18.6±4.0^∗∗	21.8±3.1^∗∗
Week 13	0.6±0.1	0.8±0.1	3.3±0.9^∗∗	13.9±2.3^∗∗	55.6±5.2^∗∗	42.8±5.1^∗∗
Catalase(nmolNADPH/minutepermg)
Day 6	253±17	234±17	177±13	162±9	302±11	292±18
Day 34	289±23	253±16	222±18	329±29	438±30^∗	476±26^∗
Week 13	274±28	281±6.0	253±22	378±28^∗	523±24^∗∗	508±29^∗∗
Mice	0ppm	10ppm	100ppm	1000ppm	4000ppm	8000ppm
AcylCoAoxidase(nmolDCF/minutepermg)
Day 6	1.2±0.1	1.0±0.0	1.1±0.1	2.5±0.1^∗	8.2±1.8^∗∗	16.5±2.2^∗∗
Day 34	1.2±0.1	1.4±0.2	1.0±0.3	2.7±0.5^∗	8.5±0.7^∗∗	15.5±0.4^∗∗
Week 13	1.2±0.1	1.4±0.1	1.1±0.1	1.7±0.1^∗	10.9±1.3^∗∗	18.0±1.7^∗∗
𝛽-Oxidation(Lazarowmethod)(nmolNADH/minutepermg)
Day 6	0.5±0.2^c	1.0±0.2	0.8±0.2	1.9±0.1^c∗∗	15.3±0.5^c∗∗	30.6±1.3^∗∗
Day 34	1.0±0.3	1.0±0.2	0.9±0.1^c	1.9±0.1^∗	19.8±1.1^∗∗	45.4±1.3^∗∗
Week 13	1.2±0.1^c	1.2±0.1	1.2±0.2	1.9±0.2	21.3±0.6^∗∗	42.2±1.5^∗∗
Carnitineacetyltransferase(nmolreducedCoA/minutepermg)
Day 6	1.2±0.1	1.4±0.2	1.4±0.1	2.6±0.3^∗∗	11.1±2.0^∗∗	17.2±0.5^∗∗
Day 34	1.7±0.2	1.3±0.1	1.2±0.1	2.7±0.3	15.7±1.3^∗	24.6±1.4^∗∗
Week 13	1.5±0.2	1.7±0.1	1.8±0.3	2.8±0.3^∗∗	18.1±0.9^∗∗	24.8±1.0^∗∗
Catalase(nmolNADPH/minutepermg)
Day 6	98.3±6.2	96.8±4.2	95.8±2.8	96.0±2.6	187.8±27.4	314.7±8.7^∗∗
Day 34	98.3±4.0	88.1±3.9	86.6±3.8	89.3±6.3	225.9±8.8	289.2±4.3^∗∗
Week 13	74.8±4.4	75.4±7.1	84.2±10.5	78.7±7.4	238.8±8.4^∗∗	302.1±11.3^∗∗
Hamsters	0ppm	100ppm	1000ppm	6000ppm	12000ppm	24000ppm
AcylCoAoxidase(nmolDCF/minutepermg)
Day 6	2.4±0.2	2.1±0.1	2.5±0.2	3.1±0.4	4.0±0.2^∗	4.4±0.6^∗
Day 34	2.1±0.2	2.3±0.2	2.3±0.2	3.1±0.2^∗	3.2±0.3^∗	4.6±0.4^∗∗
Week 13	2.2±0.1	2.2±0.1	2.1±0.1	2.9±0.1^∗∗	3.2±0.2^c∗∗	3.7±0.4^∗∗
𝛽-Oxidation(Lazarowmethod)(nmolNADH/minutepermg)
Day 6	1.9±0.1	1.9±0.5	1.7±0.1	2.2±0.4^d	2.7±0.2^c	3.0±0.2^∗∗
Day 34	2.2±0.1	1.8±0.3	2.0±0.3	2.0±0.2	1.6±0.3^c	2.0^e
Week 13	2.1±0.1	2.0±0.1	1.6±0.3	1.6±0.2	2.0±0.2^c	2.2±0.5^f
Carnitineacetyltransferase(nmolreducedCoA/minutepermg)
Day 6	8.0±0.5	8.1±0.2	7.6±0.6	10.8±0.4^∗∗	12.8±0.9^∗∗	14.1±1.6^∗∗
Day 34	7.0±0.2	6.1±0.2	8.2±0.5	7.4±0.4	9.3±0.4^∗	17.2±2.1^∗∗
Week 13	6.8±0.4	6.0±0.2	7.5±0.8	8.2±0.3	10.8±2.0^∗	14.1±2.2^∗∗
Catalase(nmolNADPH/minutepermg)
Day 6	273±21	304±9	249±25	260±37^c	251±17	226±11
Day 34	302±24	312±22	285±12	284±22	258±16	261±34
Week 13	291±19	272±17	269±26	270±10	246±14	252±13^c

^∗∗Significantly different (𝑃≤.01) from the control group by Shirley’s test; ^aMean±standarderror; ^b𝑛=5; ^c𝑛=4; ^d𝑛=3; ^e𝑛=1, no standard error presented because only one sample available; ^f𝑛=2.