Antioxidant effects of L-citrulline supplementation in high-fat diet- and dexamethasone-induced Type-2 diabetes mellitus in wistar rats (Rattus norvegicus)

Background: Oxidative stress is one of the major mechanisms underlying the onset and development of type-2 diabetes mellitus (T2DM). Although L-citrulline possesses antioxidant effect, little or no data exist linking such effects in diabetic setting. Objective: This study aimed to evaluate the effect of L-citrulline on biomarkers of oxidative stress in diabetic Wistar rats. Materials and Methods: Thirty male Wistar rats 10–12 weeks old and weighing 200–250 g were randomly assigned into six groups of five rats each. Group I rats were fed normal diet, while diabetes was induced in the other groups with high-fat diet (HFD) and dexamethasone intraperitoneally (1 mg/kg) for 21 days. Thereafter, Group III received metformin 100 mg/kg/day orally, and Groups IV, V, and VI received 200, 400, and 800 mg/kg/day L-citrulline, respectively, for another 21 days. Data were analyzed using SPSS and values at P < 0.05 were considered statistically significant. Results: The malondialdehyde concentrations were significantly reversed from 42.0 ± 0.42 μmol/mL in the diabetic group to 20.7 ± 0.81, 22.2 ± 0.75 and 22.1 ± 0.39 μmol/mL at 200, 400, and 800 mg/kg/day, respectively. The L-citrulline remarkably ameliorated the reduction in superoxide dismutase activity noted in the diabetic group (13.0 ± 0.44 μmol/mL) at all doses (17.8 ± 0.37, 16.0 ± 0.51, and 23.7 ± 0.78 μmol/mL at 200, 400, and 800 mg/kg, respectively). Similarly, there was a corresponding significant increase in the catalase activity, especially at 400 mg/kg (13.7 ± 0.43 ng/mL) and 800 mg/kg (14.6 ± 0.54 ng/mL) compared to the diabetic group (10.8 ± 0.41 ng/mL). The marked reduction in reduced glutathione level observed in the diabetic group (22.9 ± 0.69 mg/mL) was markedly ameliorated by L-citrulline supplementation at all doses (42.9 ± 1.08, 46.4 ± 0.53, and 45.2 ± 1.00 mg/mL at 200, 400, and 800 mg/kg, respectively). Conclusion: This study shows that L-citrulline supplementation has antioxidant effects in HFD- and dexamethasone-induced T2DM in male Wistar rats.