Riboflavin ameliorates mitochondrial dysfunction via the AMPK/PGC1α/HO‑1 signaling pathway and attenuates carbon tetrachloride‑induced liver fibrosis in rats

Hepatic fibrosis is a global health problem, with increasing evidence demonstrating that oxidative stress serves a pivotal role in fibrogenesis. Riboflavin is a vital nutrient in the human and animal diet, which enhances the activity of antioxidant enzymes and ameliorates oxidative stress. The present study evaluated the effect of riboflavin on liver fibrosis and the mechanisms underlying this process. Rats were subcutaneously injected with carbon tetrachloride (CCl4) dissolved in sterile olive oil twice per week to induce hepatic fibrosis. The effect of riboflavin on CCl4‑induced liver fibrosis was then assessed. Blood samples and liver tissues were collected and analyzed. The liver tissue morphological changes, immunohistochemical analysis, levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the mitochondria, and the protein expression levels of α‑smooth muscle actin (α‑SMA), transforming growth factor‑β1 (TGF‑β1), extracellular signal‑regulated kinase (ERK), p38, c‑Jun N‑terminal kinase (JNK), AMP‑activated protein kinase (AMPK), peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α) and heme oxygenase 1 (HO‑1) in the liver were also analyzed. The results demonstrated that riboflavin treatment significantly decreased the levels of alanine transaminase and aspartate transaminase in the serum, increased SOD activity and modulated the MDA level in the mitochondria. Furthermore, riboflavin significantly inhibited the CCl4‑induced, upregulated protein expression levels of phosphorylated (p)‑ERK, p‑p38, p‑JNK, TGF‑β1 and α‑SMA. Moreover, riboflavin significantly increased the expression of p‑AMPK, PGC‑1α and HO‑1 in the liver tissue. These results suggested that riboflavin delays CCl4‑induced hepatic fibrosis by enhancing the mitochondrial function via the AMPK/PGC‑1α/HO‑1 and mitogen‑activated protein kinase signaling pathways.