Clinicobiochemical and GC-MS Based Serum Metabolomics for determination of Therapeutic Efficacy of Silymarin in Pneumonic Sheep

Abstract

<title>Abstract</title> <bold>Background:</bold> The goal of this study was to evaluate the therapeutic efficacy of silymarin against sheep pneumonia utilizing clinical, biochemical and metabolomics approaches. <bold>Methods:</bold> Fifty adult male Barki sheep were divided into two groups based on their health status. Group 1 included healthy sheep (n = 10); Group 2 included sick sheep with clinical evidence of pneumonia (n = 40), which were further classified into four subgroups based on treatment protocols: subgroup 1 (SG1) was given traditional treatment; subgroup 2 (SG2) received traditional treatment plus daily 280 mg of silymarin orally; subgroup 3 (SG3) was administrated daily 280 mg of silymarin orally; and subgroup 4 (SG4) received daily 560 mg of silymarin orally. Evaluation of hepatic and renal function as well as serum lipid profile, glucose concentrations, malondialdehyde (MDA) concentrations, and total antioxidant activity (TAC) was carried out using commercial kits. Efficacy-directed distinction between therapeutic groups was accomplished based on GC-MS generated serum metabolite profiles supported by partial least squares regression analysis (PLS). <bold>Results:</bold> PLS score plot showed a clear discrimination between the healthy and pneumonic sheep groups that exhibited lower concentrations of TAC, total cholesterol, HDL-cholesterol, and glucose, but elevated liver enzyme, urea, creatinine, MDA and LDL-cholesterol (P &lt; 0.05). Through clinical evaluations, the rapid clinical responses were achieved by the oral administration of silymarin 560 mg and through selective analysis of metabolomics profile, pneumonic therapy with 280 mg of silymarin was the best therapeutic outcome relying on a SG3 was strongly correlated with the upregulation of TAC, glucose, and total and HDL-cholesterol values. <bold>Conclusions: </bold>Pneumonic sheep treated with silymarin exhibited healing as well as greater clinical, metabolomic and biochemical improvement than treatment with traditional treatment alone.