Abstract | Melatonin Ameliorates Rhabdomyolysis – Induced Acute Kidney Injury In Rats

Authors: Uppuluri A., Jain C.

Scientific advisor: Shchudrova  T. Ph.D. Department of Pharmacology Bukovinian State Medical University

Rhabdomyolysis is the disruption of skeletal muscle integrity leading to the leakage of muscle cell contents, Rhabdomyolysis can be caused by different physical or chemical damages Clinically rhabdomyolysis ranges from an asymptomatic with elevation in the  creatine kinase level to a life- threatening  condition  associated  with   kidney   injury   (AKI)   and  disseminated  intravascular coagulation. Development of AKI is caused by accumulation of nephrotoxic myoglobin in the kidney and renal hypoperfusion as a result of systemic hypovolemia. Current treatment for rhabdomyolysis- induced AKI relies on supportive therapies (IV fluids, bicarbonate, hemodialysis) and the mortality remains considerably high. Pineal hormone melatonin is known as a main regulator of biorhythms, possessing cytoprotective, antioxidant, immunomodulatory, and antiinflammatory properties under the conditions of various pathologies, including  renal, which contributes to its active study in order to expand the range of clinical use.

Research was conducted on 24  nonlinear mature white  rats randomly divided  into 3 equal groups: group I – control,  group II – rhabdomyolysis-induced AKI caused by intramuscular injection of 50%  glycerol solution (8 ml/kg), group  III – administration of melatonin at a dose of 5 mg/kg (“Sigma”, USA) 1 h and 24 h after glycerol administration. The rats were sacrificed 48 h after the glycerol injection.  It was found that  co-administration of melatonin  significantly ameliorated kidney function  in rats with AKI.

Cytoprotective effect  on  the  proximal renal tubules is verified  by 3-fold decrease in urine Gamma Glutamyl Transpeptidase(γ-GTP) level (p<0.05), and resulted in an increase in creatinine clearance by 1.4  times (p<0.05) with subsequent reduction of retention azotemia, decrease in plasma potassium level, reduction of proteinuria by 1.5 times (p<0.05), 2-fold decrease in fractional sodium excretion (p<0.05). Renoprotective effect  of melatonin may be  partially attributed to its potent antioxidant effect,  verified by an increase in Glutathione Peroxidase(GPx) activity compared to  untreated animals  (p<0.05),  as well  as  an  ability to  maintain  cellular  energy   balance  by preservation of Succinate Dehydrogenase(SDH) activity in kidney tissue. The obtained data on the effectiveness of melatonin under the conditions of rhabdomyolysis-induced AKI indicate its potent renoprotective activity resulting from the influence on the key links of pathogenesis. The results of the research confirm the prospects for further  experimental study of melatonin in conditions of various renal pathologies.

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