The ameliorative effect of pioglitazone and/or cod liver oil on hepatotoxicity induced by carbon tetrachloride in rats

Liver diseases rank among the foremost causes of mortality and morbidity worldwide. The PPARγ ligand, pioglitazone (PG), which has been clinically tested and is utilized in diabetes management, demonstrated a hepatoprotective effect in different studies. Furthermore, cod liver oil (COD) and its components exhibit a significant protective effect against hepatotoxicity in animals. This work aimed to investigate the impact of PG and/or COD on hepatotoxicity provoked by carbon tetrachloride (CCl4) in rats. Fifty albino Wistar rats were assigned to five groups (n = 10). Group I acted as a control. Group II received CCl4. Groups III and IV were administered with CCl4 and co-treated with oral PG or COD, respectively. Group V was administered with CCl4 and co-treated with both PG and COD. The duration of the experiment was 4 weeks. Liver function tests, hyaluronic acid (HA), and adiponectin levels were measured in serum. In liver tissue, adiponectin, tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) gene expressions were evaluated by RT-PCR. Moreover, histopathological examinations and alpha-smooth muscle actin (α-SMA) immunoreactivity were assessed in hepatic tissues. Histopathological alterations were improved in the group treated with combined PG and COD, as indicated by amelioration of liver function tests, as well as decreased HA and elevated adiponectin levels in serum. In hepatic tissues, there was also an upregulation of adiponectin and IL-10 and a downregulation of TNF-α gene expression. Moreover, PG and COD decreased α-SMA expression in hepatic tissues as well. These findings indicate that PG and/or COD markedly mitigate liver damage caused by CCl4 in rats; however, further large-scale studies are necessary to prove this hypothesis.