Abstract
Background: Our study aimed to assess the efficiency of Curcumin nanoformulation (LCC) on experimental nephrotoxicity induced by Gentamicin in rats. Methods: Six groups of seven rats were used: C—(control group) received saline solution i.p. (i.p. = intraperitoneal), G—gentamicin (G, 80 mg/kg body weight (b.w.)), GCC1 and GCC2—with G and CC solution (single dose of 10 mg/kg b.w.-CC1, or 20 mg/kg b.w.-CC2), GLCC1 (10 mg/kg b.w.) and GLCC2 (20 mg/kg b.w.) with G and LCC administration. Oxidative stress parameters (NOx = nitric oxide, MDA = malondialdehyde, TOS = total oxidative stress), antioxidant parameters (CAT = catalase, TAC = total antioxidant capacity), matrix metalloproteinases (MMP-2 and MMP-9), and renal function parameters (creatinine, blood urea nitrogen, and urea) were measured. Kidneys histopathologic examination was made for each group. Results: Pretreatment with CC and LCC in both doses had significantly alleviating effects on assessed parameters (NOx, MDA, TOS, CAT, TAC, MMP-2, and -9) as compared with the untreated group (p < 0.006). Histopathological aspect and renal function were significantly improved in CC and LCC groups. Liposomal formulation (LCC) showed higher efficiency on all examined parameters compared to CC (p < 0.006). Conclusions: Our results demonstrated improving renal function and kidney cytoarchitecture, oxidative stress/antioxidant/balance, and MMPs plasma concentrations with better dose-related efficacity of LCC than CC.
Highlights
Aminoglycoside antibiotics are widely used for gram-negative microorganism infections
LCC2to solution; letter codes correspond e G compared to GLCC2; A Gentamicin and CC1 solution (GCC1) compared to Gentamicin and CC2 solution (GCC2); B GCC1 compared to GLCC1; X GCC2 compared to GLCC2; α GLCC1 a b c d to the p-values < 0.006: G compared to C; G compared to GCC1; G compared to GCC2; G compared to GLCC1; e G
0.006: b c d e the p-values < 0.006: G compared to C; G compared to GCC1; G compared to GCC2; G compared to GLCC1; G
Summary
Aminoglycoside antibiotics are widely used for gram-negative microorganism infections This class comprises Gentamicin, Tobramycin, and Amikacin, their bactericidal activity being concentration-dependent [1]. In the group of aminoglycosides (antibiotics used to treat severe nosocomial gram-negative infections), Gentamicin was proved to be an effective treatment for nosocomial infections [2]. Aminoglycosides exert their antibacterial activity due to impeding bacterial synthesis of proteins by increasing cell’s membrane permeability [3]. The use of gentamicin, in parenteral administration, has shown significant better infection outcomes involving some gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and was efficient against some other strains such as Neisseria [5,6,7]. Different mechanisms of Gentamicin induced nephrotoxicity have been studied, pointing on inflammatory reaction and oxidative stress-induced renal proximal tubular epithelial cells (RPTECs) apoptosis [11]
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