Combination therapy of N-acetylcysteine,sodium nitroprusside and phosphoramidon attenuates ischemia-reperfusion injury in rat kidney

A tetrapeptide derivative PEP1261 {Boc-Lys-(Boc)-Arg-Asp-Ser-(tBu)-OtBu}, corresponding to residues 39–42 of human lactoferrin, was tested for its antiinflammatory action in adjuvant induced arthritis in rats. Administration of heat killed Mycobacterium tuberculosis (500 g/0.1 ml of paraffin oil) intradermally into the foot pad of right hind paw resulted in an increased paw volume and an increase in the levels of reactive oxygen species and -glucuronidase as well as a decrease in the antioxidants levels. PEP1261, at an effective dose of 10 mg/kg body wt., exhibited a significant antiarthritic activity as evidenced by lowering of paw volume and inhibited the free radicals toxicity by increasing the antioxidants levels. This peptide derivative was also shown to have a membrane stabilizing action by significantly decreasing the total and free activity of -glucuronidase and inhibiting the rate of release of the enzyme from lysosomal rich fraction. Histopathological studies confirmed the above results by showing a decrease in mononuclear cell infiltration, hypertrophy, hyperplasia and pannus formation after PEP1261 treatment in arthritic rats.