mber of α-SMA-positive activated hepatic stellate cells, a major fibrogenic cell, increased in response to the CL diet, but was decreased in mice treated with febuxostat and allopurinol (Fig. [3a](#Fig3){ref-type="fig"}). Consistent with the histological findings, both febuxostat and allopurinol reduced hepatic hydroxyproline, a marker of collagen fiber content (Fig. [3e](#Fig3){ref-type="fig"}). Additionally, compared with the CL group, the lower levels of plasma ALT in the febuxostat- and allopurinol-treated groups indicated an attenuation of CL diet-induced liver damage (Table [1](#Tab1){ref-type="table"}).Figure 3Febuxostat and allopurinol attenuated the development of hepatic steatosis and fibrosis in NASH mice. (**a**) Liver sections were stained with hematoxylin-eosin (H&E), Azan, and Sirius Red. α-smooth muscle actin (α-SMA)--positive hepatic stellate cells were detected by immunohistochemical staining. The original magnification was × 200. Scale bars represent 100 μm. (**b**) Triglycerides (TG), (**c**) free fatty acids (FFAs), and (**d**) total cholesterol (TC) levels in the livers. (**e**) Hydroxyproline content in the livers. Data are mean ± SEM (n = 7--8 mice per group). \*\**P* \< 0.01 *vs*. NC; ^\#^*P* \< 0.05, ^\#\#^*P* \< 0.01 *vs*. CL. A.U., arbitrary unit.

Febuxostat alleviated CL diet-induced inflammation and oxidative stress in the liver {#Sec6}
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Chemokine (C-C motif) ligand 2 (Ccl2) increases recruitment of Ccl2 receptor (Ccr2)-positive inflammatory monocytes into the liver^[@CR20]^. In response to the CL diet, the resulting influx of Ccr2-positive cells and liver-resident macrophages (Kupffer cells) produces a large amount of proinflammatory mediators and promotes insulin resistance and NASH in mice^[@CR21],[@CR22]^. Here, we observed a marked induction of *Ccl2*, *Ccr2*, and tumor necrosis factor-α (*Tnf-a*) in the liver of CL mice, which was significantly attenuated in C