OBJECTIVES: To determine the effects of melatonin combined with antibiotic administration on the suppression of renal scarring in an experimental pyelonephritis model. METHODS: The control group underwent a sham operation without infection. In the other groups, treatment began 72 hours after direct bacterial inoculation. In the no-treatment group, rats received daily intraperitoneal injections of saline. In the antibiotic-only group, the rats were treated only with ceftriaxone intramuscularly at a dose of 50 mg/kg once daily for 5 days. In the melatonin-only group, only 20 mg/kg of melatonin once daily was given by intraperitoneal injection for 5 days. In the antibiotic plus melatonin group, melatonin and ceftriaxone were administered at the same dosages and duration as for the single-modality treatment groups. After 6 weeks, the kidneys were removed for malondialdehyde measurements and histopathologic examination (inflammatory response and cicatrization). RESULTS: Melatonin only (134.25 +/- 13.42) and antibiotic plus melatonin treatment (122.62 +/- 8.91) caused a marked reduction in the mean malondialdehyde values compared with no treatment (214.12 +/- 17.77) and antibiotic-only treatment (161.37 +/- 16.03), with no significant difference compared with that of the control group (120.75 +/- 9.83). Histopathologically, in the no-treatment group, the severity of scarring correlated directly with the severity of inflammation (r = 0.93). No significant differences were found in the renal scarring scores in rats receiving no treatment and those treated only with antibiotic or melatonin. In the antibiotic plus melatonin treatment group, the cicatrization score was not statistically different from that of the control group. CONCLUSIONS: When combined with antibiotics, melatonin causes a significant inhibition of malondialdehyde production and neutrophil infiltration caused by acute pyelonephritis in an experimental rat model, and these are responsible for the protective effect of melatonin against renal damage, preventing renal scarring formation.
OBJECTIVES: To determine the effects of melatonin combined with antibiotic administration on the suppression of renal scarring in an experimental pyelonephritis model. METHODS: The control group underwent a sham operation without infection. In the other groups, treatment began 72 hours after direct bacterial inoculation. In the no-treatment group, rats received daily intraperitoneal injections of saline. In the antibiotic-only group, the rats were treated only with ceftriaxone intramuscularly at a dose of 50 mg/kg once daily for 5 days. In the melatonin-only group, only 20 mg/kg of melatonin once daily was given by intraperitoneal injection for 5 days. In the antibiotic plus melatonin group, melatonin and ceftriaxone were administered at the same dosages and duration as for the single-modality treatment groups. After 6 weeks, the kidneys were removed for malondialdehyde measurements and histopathologic examination (inflammatory response and cicatrization). RESULTS:Melatonin only (134.25 +/- 13.42) and antibiotic plus melatonin treatment (122.62 +/- 8.91) caused a marked reduction in the mean malondialdehyde values compared with no treatment (214.12 +/- 17.77) and antibiotic-only treatment (161.37 +/- 16.03), with no significant difference compared with that of the control group (120.75 +/- 9.83). Histopathologically, in the no-treatment group, the severity of scarring correlated directly with the severity of inflammation (r = 0.93). No significant differences were found in the renal scarring scores in rats receiving no treatment and those treated only with antibiotic or melatonin. In the antibiotic plus melatonin treatment group, the cicatrization score was not statistically different from that of the control group. CONCLUSIONS: When combined with antibiotics, melatonin causes a significant inhibition of malondialdehyde production and neutrophil infiltration caused by acute pyelonephritis in an experimental rat model, and these are responsible for the protective effect of melatonin against renal damage, preventing renal scarring formation.
Authors: Egor Y Plotnikov; Maria A Morosanova; Irina B Pevzner; Ljubava D Zorova; Vasily N Manskikh; Natalya V Pulkova; Svetlana I Galkina; Vladimir P Skulachev; Dmitry B Zorov Journal: Proc Natl Acad Sci U S A Date: 2013-07-29 Impact factor: 11.205