Effects of Methylprednisolone on TGF-beta, Apoptosis and Renal Scarring in Experimental Acute Pyelonephritic Weaning Rats

ABSTRACT

PURPOSE: Acute pyelonephritis of growing kidneys may result in renal scarring. TGF-beta, inflammatory cytokine, has been suggested to play an important role in promoting renal scarring through apoptosis, suppression of cellular proliferation and fibrosis. We observed the effects of a potent anti-inflammatory agent, methylprednisolone on apoptosis and renal scarring in experimentally induced acute pyelonephritic weaning rats. MATERIALS AND METHODS: To induce ascending pyelonephritis a saline solution containing Escherichia coli type ATCC No. 25922, pili-form (107 bacteria/mL) was infused into the bladder through the 16-guage silicone cannula for 48 hours to 102 three-week-old Sprague-Dawley rats (50-60g). Experimental groups were divided into three groups according to the treatment protocols, group I (ceftriaxone only, n=31), group II (methylprednisolone+ceftriaxone n=28), control group (n=43) was not treated. Histopathologic scores of inflammatory changes, fibrosis and tubular atrophy, the apoptosis index and TGF-beta1 expression score were observed at post-infection 1 and 3 week. Datas were analysed using ANOVA test and P value below 0.05 was interpreted as significant. RESULTS: The mortality rate (21.4%) of group II was not different to the control group (41.9%) and group I (32.3%). The inflammatory score of group II (0.8+/-0.87) at week 1 was significantly lower than those of the control group (2.3+/-0.87) and Group I (1.7+/-0.79) (P<0.05). Apoptosis index of group II (2.9+/-2.15) at week 1 was significantly lower than (10.0+/-0.95) and group 1 (8.3+/-2.53) (P<0.05). TGF-beta1 expression score of group II (0.8+/-0.72) at week 1 was significantly lower than those of the control group (1.9+/-0.68) and group I (1.8+/-0.60) (P<0.05). The fibrosis score of group II (1.1+/-0.10) at week 3 was significantly lower than that of the group I (1.8+/-0.83) (P<0.05). CONCLUSION: Combined treatment with methylprednisolone and ceftriaxone reduced inflammation, fibrosis, apoptosis and TGF-beta expression in acute pyelonephritic weaning rats, compared to ceftriaxone alone. Anti-inflammatory agent supplemented to antibiotics could prevent renal scarring more effectively.