Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Metabolic syndrome (MetS) induces profound pancreatic damage characterised by oxidative stress and chronic inflammation. Objectives: This study investigated the protective effects of L-citrulline (L-CIT) in the pancreas of a MetS animal model by evaluating oxidative stress responses, inflammatory cytokines, interferon gamma (IFN-?), aldose reductase (AKR1B1), glucose kinase-3?, abdominal fat and body weight. Methods: The animals (Wistar rats; Rattus norvegicus) were divided into five groups (n = 6), three of which received MetS induction via a 20% fructose solution and received oral L-CIT at escalating doses (200, 400, or 800 mg/kg). Group 1 served as the normal control, while group 2 served as the negative control (20% fructose solution). Post-treatment, pancreas samples were collected for biochemical analysis to determine the dose-dependent effects of L-CIT. Results: Pancreatic oxidative stress was significantly reduced (P< 0.05) in the L-CIT-treated groups vs the MS-untreated group. TNF-?, IL-1? and IL-6 were significantly reduced (P< 0.05) with L-CIT treatment vs the MS-untreated group. However, IL-10 was significantly increased (P < 0.05) in the L-CIT group compared with the MS-untreated group. Pancreatic IFN-? was significantly (P< 0.05) reduced in the L-CIT groups compared to the MS-untreated group, whereas the changes in pancreatic BDNF were not statistically significant. Both pancreatic AKR1B1 and GSK-3? were significantly reduced (P< 0.05) in the groups given L-CIT vs the MS-untreated group. Abdominal fat and body weight were significantly lower (P< 0.05) in the L-CIT groups than in the MS-untreated group. Conclusion: L-CIT holds promise as a therapeutic supplement for preserving pancreatic health in metabolic disease.