A Study to Evaluate the Efficacy of Saroglitazar in Non-Alcoholic Steatohepatitis Induced by High Fructose Diet Rat Model

Non-alcoholic steatohepatitis (NASH) is a clinical condition with a global prevalence of 25.24%. Peroxisome proliferator-activated receptors (PPAR) have been significantly associated with the pathogenesis of NASH. To evaluate the efficacy of saroglitazar in an animal model of NASH by evaluating the magnitude of changes in liver function tests (LFT) and histopathology. The baseline parameters of 14 male Sprague–Dawley rats were recorded and then grouped into four groups: treatment groups (high high-dose saroglitazar [HDSG] and low low-dose saroglitazar [LDSG] doses of saroglitazar), normal control, and disease control. Initially, except for the normal control, the other three groups were fed a fructose diet for 5 weeks and then all four groups were fed a standard chow diet for the next 2 weeks during which the two treatment groups were orally gavaged with saroglitazar. Changes in LFT, body weight (BW), lipid profile, oxidative stress, and histopathology were evaluated at different time points. A statistically significant reduction was found in the mean serum glutamic-oxaloacetic transaminase (SGOT) ( p = 0.0267) and serum glutamate-pyruvate transaminase (SGPT) ( p = 0.0059) between the groups at the end of treatment. As with BW changes ( p < 0.001), a significant difference was observed between the time points in HDSG and LDSG with respect to all parameters of the lipid profile assessed ( p < 0.05). Amelioration of hepatocellular ballooning and lobular inflammation in histopathology was evident in both treatment groups. Immunohistochemistry revealed loss of cytokeratin CK8/18 in disease control while it was preserved in LDSG and HDSG. The study has explicitly illustrated the improvement in the biochemical and pathological changes in the rat model of NASH induced by a high fructose diet.