prednisolone-farnesylate and Inflammation

An experimental study was performed to investigate the influence of subsidence of chronic inflammation in peripheral target tissue on the recovery of crushed nerve. Seventy-eight male Wistar rats weighing 300-370 g were used. The sciatic nerve was operatively crushed unilaterally with an aneurysm clip (250 gf) applied for 5 min. Chronic inflammation, localized to the ankle, was induced by intra-articular injection of complete Freund's adjuvant 1 week preoperatively. Prednisolone farnesylate (PNF-21) 1.4% gel was applied on the ankle as an anti-inflammatory agent for consecutive days after the operation. The animals were divided into five groups as follows: crush injury with ipsilateral arthritis (CIA); crush injury with ipsilateral arthritis and PNF-21 gel applied on the ipsilateral ankle (CIA + IPNF); crush injury with ipsilateral arthritis and PNF-21 gel applied on the contralateral ankle (CIA + CPNF); crush injury with contralateral arthritis (CCA); crush injury without arthritis (C). Specimens for histopathological examination were taken from the nerve at a site 5 mm distal to the crush lesion at 4 weeks postoperatively. The average axon diameter was significantly larger in the CIA + IPNF group than in the CIA group (p < 0.01). No significant difference was observed between the CIA + CPNF group and the CIA group. In conclusion, chronic inflammation in peripheral target tissue suppresses recovery of the crushed nerve, and subsidence of this chronic inflammation improves this suppression histopathologically.

Topics: Animals; Ankle Injuries; Arthritis, Experimental; Axons; Chronic Disease; Farnesol; Freund's Adjuvant; Inflammation; Male; Nerve Crush; Prednisolone; Rats; Rats, Wistar; Sciatic Neuropathy

The toxicity of Prednisolone farnesylate (PNF), a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF was injected subcutaneously at doses of 0.03, 0.3, 3 and 30 mg/kg/day for 13 weeks. In addition, 18.7 mg/kg/day prednisolone (PN), which is approximate to 30 mg/kg/day PNF in prednisolone molarity, was also administered to the rat for comparison. The results are summarized as follows: 1. All animals from the PN 18.7 mg/kg/day group, and four(4) out of ten(10) males and three(3) out of ten(10) females from the PNF 30 mg/kg/day group died having shown weakened condition such as unkempt fur and emaciation. Histopathologically, systemic suppurative inflammation, as shown by pyeronephritis and abscess formation in many organs and tissues, was observed and it was considered that the administration of steroid induced weakened condition and systemic suppuration which resulted in death. In addition, atrophy was noted in the adrenal glands, lymphatic organs and skin, and histopathological lesions were also observed in the lungs, liver, pancreatic islets, bone, bone marrow and mammary glands. 2. Surviving animals in the PNF 30 mg/kg/day group showed almost the same changes as those observed in the dead animals that died. Hematological examination revealed an anemic change and a decrease in lymphocytes with an increase in segmented neutrophils and eosinophils. In the urinalysis and blood chemistry, the changes suggesting damages to the liver and kidneys were mainly observed. 3. In the PNF 3 and 0.3 mg/kg/day groups, several changes such as atrophy of the adrenal glands, lymphatic organs and skin were noted in a dose dependent manner. 4. In the PNF 0.03 mg/kg/day group, ther were no toxic signs. 5. Based on these results, it was concluded that the overt toxic dose of PNF was 0.3 mg/kg/day and the non-toxic dose was 0.03 mg/kg/day in the present study.

Topics: Animals; Blood Chemical Analysis; Body Weight; Farnesol; Female; Inflammation; Injections, Subcutaneous; Kidney; Liver; Male; Organ Size; Prednisolone; Rats; Rats, Sprague-Dawley; Time Factors