title: A novel peptide derivative exhibits anti inflammatory and antioxidant activity in adjuvant induced arthritis in rats.
abstract: 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 microg/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 beta-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 beta-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.
authors.affiliation: Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India.
authors.forename: Dilly Ashok
authors.initials: DA
authors.lastname: Kumar
authors.forename: Panchatcharam
authors.initials: P
authors.lastname: Manikandan
authors.forename: Miriyala
authors.initials: M
authors.lastname: Sumitra
authors.forename: Kalidindi V S Narayana
authors.initials: KV
authors.lastname: Raju
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Gayathri
authors.forename: Natarajan
authors.initials: N
authors.lastname: Arutselvan
authors.forename: Rengarajulu
authors.initials: R
authors.lastname: Puvanakrishnan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001842:Bone and Bones / Q000378:metabolism; D004008:Diclofenac / Q000378:metabolism / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D007781:Lactoferrin / Q000627:therapeutic use*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; C402764:Boc-Lys(Boc)-Arg-Asp-Ser(tBu)-OtBu; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C056549:KRDS peptide; D004008:Diclofenac; D005966:Glucuronidase; D007781:Lactoferrin