Influence on sle-like disorder in MRL^L.(final).pptx

Influence on SLE-like disorder in MRL/lpr mice

1. Influence on SLE-like disorder in MRL/ lpr mice NITTAL VEKARIA M.PHARM PHARMACOLOGY(SEM 1 ST )

2. INTRODUCTION: An autoimmune disease affecting multiple body organs. Characterized by self-antigens. Antibodies form against double-stranded DNA (dsDNA), leading to widespread vasculitis. MRL/ Ipr mice develop severe disease with symptoms similar to human systemic lupus erythematosus (SLE). Symptoms include hyper-gammaglobulinemia and glomerulonephritis.

3. PROCEDURE:- Female MRL/ Ipr -mice (originally from Jackson Laboratories, USA), displaying distinct symptoms of SLE (between 12 and 13 weeks of age) are randomized and divided into groups of 12 animals each. At this age, the animals have already clinical manifestations of the SLE-like illness, as determined by the disease index, but have not yet developed proteinuria. Animals with early symptoms of disease are treated with various drugs, e.g., leflunomide, cyclosporin A, azathioprine, cyclophosphamide or prednisolone for 11 weeks and the survival rate and disease index of these animals are followed for 24 weeks. The disease index and urine protein level are determined once weekly.

4. Disease index: The subsequent clinical parameters are taken into consideration: Ears: reddening of the skin, deterioration of the pinna. Nose: loss of hair, wasting of the skin. Lymph nodes: detection of swollen lymph nodes on any part of the body, especially neck and extremities. Fur: general condition of fur (e.g. shabby, mangy, etc.), loss of hair. Skin: inflammation of the skin, scab and/ or granuloma formation. Eyes: exophthalmos, deterioration due to inflammation, tumor formation around the eye, swelling of the eyelid with eventual closure of the eye. Paws: reddening of the skin, swelling of the paw.

5. EVALUATION:-  A score for each of the above described parameters is given according to the severity of the symptoms as follows: POINTS FOR CLINICAL INDEX INVOLVEMENT DETECTABLE MODERATE SEVERE EARS(EACH) 0.5 1.0 1.5 NOSE 1.0 2.0 3.0 LYMPH NODE(EACH) 1.0 2.0 3.0 FUR 1.0 2.0 3.0 SKIN 1.0 2.0 3.0 EYES(EACH) 1.0 2.0 3.0 PAWS(EACH) 0.5 1.0 1.5

6. Body weight (one point for 5g difference from week to week) The determination of the disease index is performed, weekly, by the same individual, but without knowledge of the group being evaluated. The points, for each animal , are registered and the total score, of each group, summarized. The average score for the group is calculated, significance between the experimental group and the untreated diseased group is determined using the Student t-test. Proteinuria Pooled urine is collected from each experimental group and the amount of protein in the urine is calculated.

7. REFRENCE:- VOGEL HG,EDITOR DRUG DISCOVERY and evaluation:pharmacological assays. Springer science & business media; 2002 jun 13. Tripathi kd . Essentials of medical pharmacology. Jp medical ltd;2013 sep 30. Gupta sk. Drug screening methods jaypee brothers;2004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042628/#:~:text=The%20SLE%20symptoms%20attributed%20to,autoimmunity%20%5B39%2C%2040%5D