A novel peptide derivative exhibits anti inflammatory and antioxidant activity in adjuvant induced arthritis in rats.
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.
Kumar
Dilly Ashok
DA
Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India.
Manikandan
Panchatcharam
P
Sumitra
Miriyala
M
Raju
Kalidindi V S Narayana
KV
Gayathri
Chandrasekar
C
Arutselvan
Natarajan
N
Puvanakrishnan
Rengarajulu
R
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
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