Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress

Garrett, Qian; Khandekar, Neeta; Shih, Sharon; Flanagan, Judith; Simmons, Peter A.; Vehige, Joseph; Willcox, Mark

doi:10.1016/j.exer.2012.12.001

Cited by 62 publications

(42 citation statements)

References 77 publications

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“…57 Our previous in vitro studies using cultured human corneal epithelial cells demonstrated that exogenous osmoprotectants L-carnitine (Garrett Q. IOVS 2012;53:ARVO E-Abstract 564; Willcox MD. IOVS 2012;53:AR-VO E-Abstract 564) and betaine 24 could help stabilize corneal epithelial cell volume under hyperosmotic stress and limit hyperosmotic stress-induced apoptosis. Among the compounds tested, L-carnitine demonstrated the greatest ability.…”

Section: Discussionmentioning

confidence: 99%

“…47 Hyperosmolarity is known to induce ocular surface epithelial apoptosis both in vitro (Garrett Q. IOVS 2011;52:ARVO EAbstract 290-D754; Garrett Q. IOVS 2012;53:ARVO E-Abstract 564; Willcox MD. IOVS 2012;53:ARVO E-Abstract 564) 16,24,19,[48][49][50][51][52][53][54] and in vivo. 13,26 In the present study, we also observed corneal epithelial apoptosis in ICES-induced murine dry eyes.…”

Section: Discussionmentioning

confidence: 99%

“…The concentrations of the test compounds were determined based on the previously published data where addition of L-carnitine (10-15 mM), erythritol (20-40 mM), or betaine (10 mM), to hyperosmolar media demonstrated osmoprotection of cultured human corneal epithelial cells. 23,24 As well, the addition of betaine or L-carnitine at 10 mM, or erythritol at 40 mM, to the culture medium had no effect on viability of the cultured corneal epithelial cells. 23 …”

Section: Compound Administration Schedulesmentioning

confidence: 99%

“…IOVS 2012;53:ARVO E-Abstract 564). 24 Further, in dry-eye patients, reduced levels of tear Lcarnitine compared with healthy subjects have been reported, 25 suggesting that carnitine might play a contributory role in the development of dry eye.…”

mentioning

confidence: 99%

“…15,26,27 Using this animal model, the present study extended the previous in vitro studies of osmoprotectants (Garrett Q. IOVS 2012;53:ARVO E-Abstract 564; Willcox MD. IOVS 2012;53:ARVO E-Abstract 564) 23,24 to determine the efficacy of osmoprotectants L-carnitine, betaine, and erythritol in protection and therapeutic treatment of ICESinduced murine dry eye. …”

mentioning

confidence: 99%

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Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Compound Administration Schedulesmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye

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Invest. Ophthalmol. Vis. Sci.

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Thermo‐Responsive Microemulsions Containing Deep Eutectic‐Based Antibiotic Formulations for Improved Treatment of Resistant Bacterial Ocular Infections

Pedro

Gomes

Vilela

et al. 2023

Advanced Therapeutics

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The rise of antibiotic resistant strains, as methicillin-resistant Staphylococcus aureus (MRSA), challenges the current treatment of infections. In the case of ocular infections, antibiotic eye drops are commonly prescribed. However, their efficacy is usually compromised by the low viscosity of these formulations and the eye drainage. To overcome these drawbacks, deep eutectic solvent (DES)-based microemulsions with thermo-responsive character, that increase their viscosity upon contact with the eye have been developed. Using betaine-based DES aqueous solutions, it is possible to increase up to 140-fold the water solubility of the antibiotic chloramphenicol, typically used in ocular infections. The DES solutions containing the antibiotic are applied as water phases in water-in-oil-in-water (w/o/w) microemulsions, being stable up to 3 months. Furthermore, a sustained-release and a higher permeation of the antibiotic through the cornea than that of commercialized eye drops is achieved, while presenting comparable cytotoxicity profiles (cell viabilities > 88%). Higher antimicrobial activity and faster action of the antibiotic in case of infection with MRSA is observed compared to the commercialized formulations (7 log 10 of inactivation in 48 h vs 72 h). Overall, these microemulsions comprising DES are a promising strategy to achieve higher antibiotic effectiveness in the treatment of resistant bacterial infections.

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Betaine downregulates microRNA 34a expression via a p53‐dependent manner in cisplatin‐induced nephrotoxicity in rats

Hussein

Al-Dalain

2021

J Biochem & Molecular Tox

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Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NF k B, and IL-1β compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NF k B, and IL-1β as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

show abstract

Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress

Cited by 62 publications

References 77 publications

Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye

Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye

Thermo‐Responsive Microemulsions Containing Deep Eutectic‐Based Antibiotic Formulations for Improved Treatment of Resistant Bacterial Ocular Infections

Betaine downregulates microRNA 34a expression via a p53‐dependent manner in cisplatin‐induced nephrotoxicity in rats

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