Curcumin alleviates colistin-induced nephrotoxicity and neurotoxicity in rats via attenuation of oxidative stress, inflammation and apoptosis

Edrees, Nagah; Galal, Azza A.A.; Monaem, Aliaa R. Abdel; Beheiry, Rasha R.; Metwally, Mohamed M.M.

doi:10.1016/j.cbi.2018.08.012

Cited by 62 publications

(54 citation statements)

References 80 publications

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“…A similar molecular mechanism has also been detected in the protection of curcumin against gentamicin-induced nephrotoxicity in rats [ 107 ]. Consistent with these findings, curcumin supplementation (e.g., at 200 mg/kg/day for 6 days) can also markedly improve colistin-induced nephrotoxicity via the inhibition of oxidative stress, apoptosis, NO signaling and inflammatory response (i.e., decreases the tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6] in the kidney tissue) in a rat model [ 27 ]. Our recent data reveal that curcumin after oral administration at 50 and 200 mg/kg/day for 7 days can be detected and accumulated in multiple organs of mice, including kidney tissues [ 25 ].…”

Section: Polymyxin-induced Nephrotoxicity and Protective Effect Ofmentioning

confidence: 81%

“…Our recent studies showed that colistin treatment (200 μM) of N2a neuronal cells downregulated the expression of mammalian target of rapamycin (mTOR) and phospho (p)-p70S6 kinase (p70s6k) and upregulates unc-51 like autophagy activating kinase 1 (ULK1) expression, suggesting that mTOR inhibition-mediated autophagy is triggered in the process of colistin-induced apoptosis in neuronal cells [ 128 ]. In addition, colistin-induced neuronal cell death also involves p53, MAPK and PI3 K/Akt/c-AMP response element-binding (CREB) pathways, and their roles are shown in Figure 4 [ 26 , 27 , 78 , 81 , 132 , 142 , 146 , 147 , 148 , 149 , 150 ].…”

Section: Colistin-induced Neurotoxicity and Protective Effects Of mentioning

confidence: 99%

“…Curcumin supplementation effectively protects against colistin treatment-induced neurotoxicity in vitro (e.g., mouse primary and N2a neuronal cells) and animal models (e.g., mice and rats) ( Figure 4 ) [ 25 , 26 , 27 ]. Curcumin indicated the potential application as a neuroprotective agent with an ability to cross the BBB [ 40 , 151 , 152 ].…”

Section: Colistin-induced Neurotoxicity and Protective Effects Of mentioning

confidence: 99%

“…Natural products have been the source of most of our antibacterial armamentarium and efforts over the last 30 years [ 22 ]. Recent studies have shown that combining polymyxins with curcumin has many pharmacological and toxicological benefits over monotherapy with each compound per se including: (1), the in vitro synergy against various strains of MDR bacteria [ 23 ], including polymyxin resistant isolates [ 24 ]; (2), protection against polymyxin-induced nephron- and neuro-toxicity [ 25 , 26 , 27 ]; (3), curcumin supplementation improves recovery from the bacterial infection or LPS—induced inflammatory response or sepsis [ 28 , 29 , 30 , 31 , 32 , 33 ]. Importantly, human clinical trials indicated that curcumin displays good safety and tolerability [ 34 , 35 , 36 ]; oral administration of curcumin at eight grams per day over three months or a single oral dose of 12 grams has no marked adverse effect [ 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

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Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment

et al. 2020

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The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens.

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Section: Polymyxin-induced Nephrotoxicity and Protective Effect Ofmentioning

confidence: 81%

Section: Colistin-induced Neurotoxicity and Protective Effects Of mentioning

confidence: 99%

Section: Colistin-induced Neurotoxicity and Protective Effects Of mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment

et al. 2020

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“…4 Colistin, which has previously been limited in its use due to the incidence of adverse effects including nephrotoxicity and neurotoxicity, is resurfacing more frequently for treatment. 5,6 It is oen used to treat multi-resistant Gram-negative bacteria, where other antibiotics are no longer effective. Colistin's mechanism relies on the electrostatic interaction between the negatively charged phosphate groups of the lipopolysaccharide (LPS) bacterial outer cell membrane and the positively charged amino groups of Colistin.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles in an antibiotic-loaded nanomesh for drug delivery

et al. 2019

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Liposomes Co‐Delivering Curcumin and Colistin to Overcome Colistin Resistance in Bacterial Infections

Qin

Tang

Gan

et al. 2023

Adv Healthcare Materials

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Antibiotic colistin is the last line of defense against multidrug‐resistant (MDR) Gram‐negative bacterial infections. Emergence of colistin resistance in microbes is a critical challenge. Herein, curcumin is discovered, for the first time, to reverse the resistance phenotype of colistin‐resistant bacteria via a checkerboard assay. For the co‐delivery of curcumin and colistin, negatively charged poly(ethylene glycol)‐functionalized liposomes encapsulating both drugs (Lipo‐cc) are prepared. Killing kinetics and live/dead assays confirm the antibacterial activity of Lipo‐cc against colistin‐resistant bacteria, which is more potent than that of the free curcumin and colistin combination. Mechanistical studies reveal that Lipo‐cc restores the affinity of colistin for the bacterial membrane and improves the uptake of curcumin, which leads to reduced efflux pump activity, achieving a synergistic effect of colistin and curcumin. At the effective antibacterial dose, Lipo‐cc does not exhibit any toxicity. The therapeutic efficacy of Lipo‐cc is further demonstrated in an intestinal bacterial infection model induced with colistin‐resistant Escherichia coli. Lipo‐cc reduces the bacterial burden with over 6‐log reduction and alleviated inflammation caused by infection. Importantly, unlike colistin, Lipo‐cc does not affect the homeostasis of the intestinal flora. Taken together, Lipo‐cc successfully overcame colistin resistance, indicating its potential for the treatment of colistin‐resistant bacterial infections.

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Curcumin alleviates colistin-induced nephrotoxicity and neurotoxicity in rats via attenuation of oxidative stress, inflammation and apoptosis

Cited by 62 publications

References 80 publications

Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment

Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment

Nanoparticles in an antibiotic-loaded nanomesh for drug delivery

Liposomes Co‐Delivering Curcumin and Colistin to Overcome Colistin Resistance in Bacterial Infections

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