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

Table 3

Incidence and severity of liver histopathologic lesions in male core study Harlan Sprague Dawley rats, B6C3F1 mice, and Syrian hamsters following exposure to gemfibrozil in feed for 14 weeks^a.

Rats	0 ppm	10 ppm	100 ppm	1000 ppm	8000 ppm	16000 ppm
Liver, Cytoplasmic Alteration	0	7^b∗∗ (1.0)^c	10^∗∗ (2.0)	10^∗∗ (3.0)	10^∗∗ (4.0)	10^∗∗ (4.0)
Mice	0 ppm	10 ppm	100 ppm	1000 ppm	4000 ppm	8000 ppm
Liver, Cytoplasmic Alteration	0	NE	0	7^∗∗ (1.0)	10^∗∗ (2.6)	10^∗∗ (3.0)
Hamsters	0 ppm	100 ppm	1000 ppm	6000 ppm	12000 ppm	24000 ppm
Liver, Glycogen Depletion	0	5^d∗∗ (1.0)	4^∗ (1.0)	8^∗∗ (1.0)	9^∗∗ (1.0)	10^∗∗ (2.8)

^∗Significantly different (𝑃≤.05) from the control group by the Fisher exact test; ^∗∗𝑃≤.01; NE=not examined; ^a𝑛=10; ^bIncidence; ^cMeanseverity: 1 = minimal, 2 = mild, 3 = moderate, 4 = marked; ^d𝑛=9.