L-carnitine protects against cyclosporine-induced pancreatic and renal injury in rats.

BACKGROUND L-carnitine has protective effects against various types of injury. This study was designed to evaluate the beneficial effects of L-carnitine on pancreatic and renal injuries caused by cyclosporine (CsA). METHODS Rats maintained on a low sodium diet were given vehicle (olive oil, 1 mL/kg/d), CsA (15 mg/kg/d), L-carnitine (50 or 200 mg/kg/d), or a combination of CsA and L-carnitine for 4 weeks. The impact of L-carnitine on pancreatic injury was assessed by blood glucose levels, plasma insulin concentrations, and hemoglobulin A1c (HbA1c). In addition, the protective effects of L-carnitine against CsA-induced kidney injury were evaluated in terms of renal function, histopathology (inflammatory cell influx and tubulointerstitial fibrosis), oxidative stress (8-hydroxy 2'-deoxyguanosine, 8-OHdG), transforming growth factor-betal (TGF-β1), apoptosis (caspase-3), and autophagy (LC3-II). RESULTS CsA treatment caused diabetes, renal dysfunction, tubulointerstitial inflammation (ED-1-positive cells), and fibrosis, which were accompanied by an increase in 8-OHdG production and upregulation of TGF-β1, caspase-3, and LC3-II. Concomitant administration of L-carnitine increased plasma insulin concentrations, decreasing plasma glucose and HbA1c levels. In the kidney, L-carnitine induced dose-dependent improvement of renal function, inflammation, and fibrosis in parallel with suppression of the expression of TGF-β1 and 8-OHdG. Furthermore, the administration of L-carnitine at a high dose inhibited the expression of caspase-3 and LC3-II. CONCLUSION These findings suggest that L-carnitine has a protective effect against CsA-induced pancreatic and renal injuries.