Renoprotective Effect Of Melatonin In Conditions Of Acute Kidney Injury And Altered Pineal Gland Activity

INTRODUCTION: Melatonin is a promising therapeutic agent due to its multiple beneficial effects, wide availability and relatively high safety. As melatonin acts as a chronobiotic agent, its adequate production by the pineal gland allows for adaptation to environmental changes, while disturbances in melatonin secretion are associated with health disorders. The renoprotective effect of exogenous melatonin was established on different experimental models of acute kidney injury (AKI), while the influence of the altered pineal gland activity on the efficacy of melatonin treatment has not been investigated. OBJECTIVES: The aim of this research was to study the renoprotective potential of melatonin in conditions of aminoglycoside-induced AKI against the background of pineal hypo- and hyperfunction. METHODS: Nonlinear mature white rats (n=40) were randomly divided into 5 groups. Animals from the I (Control), and II (AKI) group were kept under the natural light regimen. Pineal hypofunction was simulated in rats from the III group by maintenance under conditions of constant light at 500 lux (24.00 light : 0.00 darkness) for 7 days. Pineal hyperfunction was simulated in rats from the IV group by maintenance under conditions of constant darkness (0.00 light : 24.00 darkness). Toxic AKI (II-IV groups) was induced by daily administration of gentamicin at a dose of 80 mg/kg for 6 days. Animals from the III-IV groups were injected daily with melatonin at a dose of 5 mg/kg. 24 h after the last injection biochemical and histological examination was performed. For the statistical analysis SPSS 17.0 software was used. RESULTS: Nephrotoxicity of gentamicin caused significant (p<0.05) functional changes and structural alterations to the rat kidneys. Treatment with melatonin in conditions of gentamicin-induced kidney injury significantly limited the degree of damage to renal tissue and prevented a critical reduction in kidney function, confirming a protective effect of melatonin. At the same time, significant (p<0.05) differences between the indices of the III and IV group allow us to state, that treatment with exogenous melatonin on the background of endogenous melatonin deficiency was less effective in comparison to the administration of melatonin in conditions of pineal hyperfunction. CONCLUSION: Melatonin ameliorates gentamicin-induced kidney injury by the limitation of histopathological changes in kidney tissue and the preservation of kidney function. Pre-existing deficiency of endogenous melatonin decreases the resistance of kidneys to the damaging action of the toxin and lessens the protective effect of the exogenous melatonin. Alternatively, in rats with increased pineal gland activity and melatonin production, co-treatment with exogenous melatonin more effectively protects the kidney from gentamicin-induced structural and functional changes and prevents the development of renal failure. Classification-JEL: