Renal Tissue Damage After Experimental Pyelonephritis: Role of Antioxidants and Selective Cyclooxygenase-2 Inhibitors

Abstract

To investigate the involvement of oxidative stress in the pathogenesis of acute pyelonephritis, and to evaluate the impact of meloxicam and/or L-carnitine in addition to conventional antibiotic treatment. A total of 48 Wistar rats were divided into 4 groups according to their treatment, which was started 1 day after inoculation of all rats with Escherichia coli (ATCC 25 922, 10(10) cfu/mL). Group 1 received only antibiotic treatment with ceftriaxone (50 mg/kg, IM). Groups 2 and 3 received L-carnitine (500 mg/kg, IM) and meloxicam (3 mg/kg, IM) in addition to conventional treatment, respectively. Group 4 received combination therapy (L-carnitine and meloxicam) in addition to the first group. Rats were killed 3 and 7 days after E. coli inoculation and underwent nephrectomy. Histologic determination of tubular atrophy, acute and chronic inflammation, interstitial fibrosis and biochemical determination of superoxide dismutase and catalase activity, total thiol content, total antioxidant capacity, and malondialdehyde and protein hydroperoxide levels were measured. Interstitial fibrosis (P = .06), chronic inflammation (P = .536), and tubular atrophy (P = 0.094) decreased in group 4 compared with the other groups, but there was a statistically significant decrease only in acute inflammation (P = .015). In addition, if the day of nephrectomy is considered, there was again a significant decrease in acute inflammation on day 7 compared with day 3 in groups 2, 3, and 4 (P = .002). Catalase significantly increased in group 2 (P = .029), group 3 (P = .02), and group 4 (P = .014), and decreased in group 1 (P = .012) in day 7. L-carnitine and meloxicam alleviated oxidative stress, probably by decreasing lipid peroxidation and enforcing antioxidant defense system. Acute renal inflammatory injury can be prevented much more effectively by combination therapy rather than by conventional therapy alone.