Thyme Extract Alleviates High-Fat Diet-Induced Obesity and Gut Dysfunction.

Prolonged intake of a high-fat diet (HFD) disturbs the composition of gut microbiota, contributing to the development of metabolic diseases, notably obesity and increased intestinal permeability. Thyme (Thymus vulgaris L.), an aromatic plant, is known for its several therapeutic properties. In this study, we explored the potential of thyme extract (TLE) to mitigate HFD-induced metabolic derangements and improve the gut environment. Eight-week-old C57BL/6 mice were administered 50 or 100 mg/kg TLE for eight weeks. Administration of 100 mg/kg TLE resulted in decreased weight gain and body fat percentage, alongside the regulation of serum biomarkers linked to obesity induced by a HFD. Moreover, TLE enhanced intestinal barrier function by increasing the expression of tight junction proteins and ameliorated colon shortening. TLE also altered the levels of various metabolites. Especially, when compared with a HFD, it was confirmed that 2-hydroxypalmitic acid and 3-indoleacrylic acid returned to normal levels after TLE treatment. Additionally, we investigated the correlation between fecal metabolites and metabolic parameters; deoxycholic acid displayed a positive correlation with most parameters, except for colon length. In contrast, hypoxanthine was negatively correlated with most parameters. These results suggest a promising role for thyme in ameliorating obesity and related gut conditions associated with a HFD.

Hippophae rhamnoides L. leaf extracts alleviate diabetic nephropathy via attenuation of advanced glycation end product-induced oxidative stress in db/db mice.

Diabetes mellitus leads to chronic complications, such as nephropathy. Diabetic complications are closely related to advanced glycation end products (AGEs). Excessive formation and accumulation of AGEs in diabetic renal diseases lead to excessive oxidative stress, resulting in chronic renal failure. The leaves of Hippophae rhamnoides L. (sea buckthorn leaves; SBL) show biological benefits, including antioxidant effects. This study aimed to evaluate the effect of SBL on kidney damage in db/db mice. The SBL extract was orally administered at 100 and 200 mg kg-1 for 12 weeks to db/db mice. Histological changes and the urine albumin/creatinine ratio were relieved, and the accumulation of AGEs in kidney glomeruli decreased following SBL treatment. Moreover, the SBL extract reduced the expression of AGEs, the receptor for AGEs, and NADPH oxidase 4, but upregulated glyoxalase 1 in the diabetic renal tissue. Urinary excretion levels and expression of 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative stress decreased after SBL treatment in the renal tissue. Furthermore, SBL attenuated oxidative stress in diabetic kidneys by reducing AGE accumulation, thereby ameliorating renal damage. Therefore, from these results, we infer that the SBL extract can act as a potential therapeutic agent for diabetic renal complications caused by AGEs.

Prebiotic and Anti-Adipogenic Effects of Radish Green Polysaccharide.

Radish (Raphanus sativus L.) greens are consumed as a source of nutrition, and their polysaccharides such as rhamnogalacturonan-I possess certain beneficial properties. This study investigated the prebiotic effects of a radish green polysaccharide (RGP) on gut health and obesity. The prebiotic activity of RGP was evaluated based on the pH changes and short-chain fatty acids (SCFAs) concentration. The results showed that 0.5% RGP had a higher prebiotic activity score than inulin and increased SCFAs production in all five prebiotic strains. Moreover, RGP inhibited fat accumulation in 3T3-L1 adipocytes, indicating its potential to reduce obesity. Overall, these findings suggested that the polysaccharide of radish greens has prebiotic effects and may serve as a beneficial prebiotic for gut health and obesity.

Protective effect of Schizonepeta tenuifolia Briq. ethanolic extract against UVB-induced skin aging and photodamage in hairless mice.

The purpose of this study was to illuminate the mechanism by which Schizonepeta tenuifolia Briq. (ST) ethanolic extract prevents skin photoaging in HR-1 hairless mice (HR-1). The ST ethanolic extract alleviated wrinkle formation, epidermal skin thickness, and collagen degradation in skin tissues of ultraviolet B (UVB)-irradiated HR-1 mice. Expression of matrix metalloproteinases (a wrinkle-related marker) was reduced, and tissue inhibitor of metalloproteinase 1 expression was upregulated following application of ST ethanolic extract. Furthermore, skin dehydration and levels of hyaluronidase-1 and -2 (enzymes that break hyaluronic acid) were decreased. Moreover, protein expression of hyaluronan synthases (markers of skin hydration) and hyaluronic acid levels increased following ST ethanolic extract treatment in UVB-induced photoaging HR-1 mice. In addition, the phosphorylation of mitogen-activated protein kinases (MAPKs), including p38, extracellular signal-regulated kinase, and Jun N-terminal kinase was suppressed, and expression of nuclear factor-kappa was reduced. Treatment with ST ethanolic extract also reduced advanced glycation end product (AGE) accumulation and expression of the receptor for AGE (RAGE) in skin tissue. These results suggest that ST ethanolic extract moderates skin damage caused by UVB irradiation via regulating the expression of wrinkle- and hydration-related proteins, MAPKs, and RAGE.

Comparison of body size perception of young women in Korea and the United States.

Body size perception among young women in Asian and Western countries is believed to be quite different, however, there are no confirming studies. We analyzed the data from young women aged between 20 and 40 who participated in the National Health and Nutrition Examination Survey (2001-2018) of the United States (US) and Korea. US young women had higher rates of being overweight and obesity than Korean young women, and there was no significant change over 20 years. In both countries, the percentage of properly estimating one's own weight exceeded 70 percent and remained relatively steady. The percentage of overestimating one's own weight was only about 10 percent in Korea in 2001, but increased to 20 percent. In the case of the US, the percentage was about 15 percent in 2001-2002, but has since continued to decline. The percentage of underestimating one's own body weight was about 18 percent in Korea in 2001, but decreased to about 8 percent. In the case of the US, the percentage was very low at about 10 percent in 2001-2002, but gradually increased to about 18 percent in 2017-2018. In conclusion, young women in the US tend to underestimate their body size, and those in Korea tend to overestimate it.

Glycolaldehyde induces synergistic effects on vascular inflammation in TNF-α-stimulated vascular smooth muscle cells.

Atherosclerosis is a chronic inflammatory disease that contributes to disease progression is associated with the expression of adhesion molecules in vascular smooth muscle cells (VSMCs). Glycolaldehyde (GA) has been shown to impair cellular function in various disorders, including diabetes, and renal diseases. This study investigated the effect of GA on the expression of adhesion molecules in the mouse VSMC line, MOVAS-1. Co-incubation of VSMCs with GA (25-50 µM) dose-dependently increased the protein and mRNA level of Vcam-1 and ICAM-1. Additionally, GA upregulated intracellular ROS production and phosphorylation of MAPK and NK-κB. GA also elevated TNF-α-induced PI3K-AKT activation. Furthermore, GA enhanced TNF-α-activated IκBα kinase activation, subsequent IκBα degradation, and nuclear translocation of NF-κB. These findings suggest that GA stumulated VSMC adhesive capacity and the induction of VCAM-1 and ICAM-1 in VSMCs through inhibition of MAPK and NF-κB signaling pathways, providing insights into the effect of GA to induce inflammation within atherosclerotic lesions.

Lactococcus lactis KF140 Reduces Dietary Absorption of Nε - (Carboxymethyl)lysine in Rats and Humans via ß-Galactosidase Activity.

Background and Aims: Excessive intake of advanced glycation end products (AGEs), which are formed in foods cooked at high temperatures for long periods of time, has negative health effects, such as inflammatory responses and oxidative stress. Nε-(Carboxymethyl)lysine (CML) is one of the major dietary AGEs. Given their generally recognized as safe status and probiotic functionalities, lactic acid bacteria may be ideal supplements for blocking intestinal absorption of food toxicants. However, the protective effects of lactic acid bacteria against dietary AGEs have not been fully elucidated. Materials and Methods: We investigated the effect of treatment with Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, on the levels and toxicokinetics of CML. The CML reduction efficacies of the Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, were conducted by in vitro test for reducing CML concentration of the casein-lactose reaction product (CLRP) and in vivo test for reducing serum CML level of LL-KF140 administered rats at 2.0 × 108 CFU/kg for14 days. In addition, 12 volunteers consuming LL-KF140 at 2.0 × 109 CFU/1.5 g for 26 days were determined blood CML concentration and compared with that before intake a Parmesan cheese. Results: Administration of LL-KF140 reduced serum CML levels and hepatic CML absorption in rats that were fed a CML-enriched product. In a human trial, the intake of LL-KF140 prevented increases in the serum levels of CML and alanine aminotransferase after consumption of a CML-rich cheese. LL-KF140 was determined to presence in feces through metagenome analysis. Furthermore, ß-galactosidase, one of the L. lactis-produced enzymes, inhibited the absorption of CML and reduced the levels of this AGE, which suggests an indirect inhibitory effect of LL-KF140. This study is the first to demonstrate that an L. lactis strain and its related enzyme contribute to the reduction of dietary absorption of CML.

Therapeutic Potential of Phlorotannin-Rich Ecklonia cava Extract on Methylglyoxal-Induced Diabetic Nephropathy in In Vitro Model.

Advanced glycation end-products (AGEs) play a vital role in the pathogenesis of diabetic complications. Methylglyoxal (MGO), one of the major precursors of AGEs, is a highly reactive dicarbonyl compound that plays an important role in the pathogenesis of diabetic nephropathy. This study was designed to evaluate the therapeutic potential of phlorotannin-rich Ecklonia cava extract (ECE) on MGO-induced diabetic nephropathy in in vitro models using mouse glomerular mesangial cells. ECE showed anti-glycation activity via breaking of AGEs-collagen cross-links and inhibition of AGEs formation and AGE-collagen cross-linking formation. The renoprotective effects were determined by assessing intracellular reactive oxygen species (ROS) and MGO accumulation, cell apoptosis, and the Nrf-2/ARE signaling pathway. MGO-induced renal damage, intracellular ROS production level, and MGO-protein adduct accumulation were significantly decreased by pretreating ECE. Moreover, ECE pretreatment exhibited preventive properties against MGO-induced dicarbonyl stress via activation of the Nrf2/ARE signaling pathway and reduction of RAGE protein expression in mouse glomerular mesangial cells. Collectively, these results indicated potential anti-glycation properties and prominent preventive effects of ECE against MGO-induced renal damage. Additionally, ECE may be utilized for the management of AGE-related diabetic nephropathy.

Glycolaldehyde, an Advanced Glycation End Products Precursor, Induces Apoptosis via ROS-Mediated Mitochondrial Dysfunction in Renal Mesangial Cells.

Glycolaldehyde (GA) is a reducing sugar and a precursor of advanced glycation end products (AGEs). The role of precursor and precursor-derived AGEs in diabetes and its complications have been actively discussed in the literature. This study aimed to elucidate the mechanism of GA-induced apoptosis in renal cells. Immunoblotting results showed that GA (100 µM) caused cytotoxicity in murine renal glomerular mesangial cells (SV40 MES 13) and induced apoptosis via major modulators, decreasing Bcl-2 and increasing Bax, cytochrome c, and cleaved caspase-3/-9 expression. GA-derived AGE accumulation and receptor for AGE (RAGE) expression increased in mesangial cells; however, cells that were cotreated with aminoguanidine (AG) showed no increase in GA-derived AGE concentration. Furthermore, reactive oxygen species (ROS) production was increased by GA, while AG inhibited AGE formation, leading to a decrease in ROS levels in mesangial cells. We evaluated apoptosis through fluorescence-activated cell sorting, and used TUNEL staining to study DNA fragmentation. Additionally, we measured ATP generation and used MitoTracker staining to access changes in mitochondrial membrane potential. This study showed that GA increased AGE concentration, RAGE expression, and excessive ROS generation, leading to renal mesangial cell damage via GA-induced apoptosis pathway caused by mitochondrial dysfunction.

Dietary rhamnogalacturonan-â rich extracts of molokhia ameliorate high fat diet-induced obesity and gut dysbiosis.

Obesity is a global health issue associated with increased prevalence of disease and mortality. Molokhia (Corchorus olitorius L.) leaves, used as vegetables in Asia and Africa, comprise abundant water-soluble mucilage polysaccharides. The present study aimed to evaluate the effects of molokhia leaf polysaccharide fraction (MPF) on high-fat diet (HFD)-induced obesity and gut dysbiosis in mice. A significant decrease was observed in the body weight, adipocyte size, triglyceride serum, and low-density lipoprotein cholesterol levels, as well as in the expression of lipid synthesis-related proteins in mice treated with 4 mg/kg of MPF (MPF4). Moreover, the expression of the tight junction protein increased significantly; however, gut permeability and related inflammatory marker levels decreased in the MPF4 group. Furthermore, MPF ameliorated gut dysbiosis, whereas the MPF4 group presented a decreased Firmicutes to Bacteroidetes ratios and an increased abundance of Akkermansia during exposure to HFD. Our findings reveal that rhamnogalacturonan-Ⅰ rich MPF attenuates obesity in mice subjected to HFD by modulating the gut microbiota.

Inhibitory effect of sea buckthorn extracts on advanced glycation endproduct formation.

This study shows the inhibitory effect of sea buckthorn (Hippophae rhamnoides L.) extracts, sea buckthorn leaf (HRL) and berry (HRB), on the formation of advanced glycation endproducts (AGEs), closely linked to diverse disease. In vitro assay revealed the superior inhibitory effect of HRL on the AGEs formation and AGEs-induced collagen crosslinking compared with that of HRB. Ultra-performance liquid chromatography-mass spectrometry results revealed that HRL displays a higher inhibition efficiency on the AGEs formation at 30 AGEs binding sites in bovine serum albumin than HRB. The high concentration of 3-sophoroside-7-rhamnoside in HRL compared with that in HRB may result in the strong inhibitory effect of HRL compared with that of HRB. HRL also exhibited significantly higher ABTS and DPPH radical scavenging activities than HRB. Overall, this study demonstrated that HRL has excellent potential as a dietary agent for controlling various diseases mediated by AGEs and oxidative stress.

Glyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Oxidative Damage and Inflammatory Response by Interacting with RAGE.

The glyoxal-lysine dimer (GOLD), which is a glyoxal (GO)-derived advanced glycation end product (AGE), is produced by the glycation reaction. In this study, we evaluated the effect of GOLD on the oxidative damage and inflammatory response in SV40 MES 13 mesangial cells. GOLD significantly increased the linkage with the V-type immunoglobulin domain of RAGE, a specific receptor of AGE. We found that GOLD treatment increased RAGE expression and reactive oxygen species (ROS) production in mesangial cells. GOLD remarkably regulated the protein and mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glyoxalase 1 (GLO1). In addition, mitochondrial deterioration and inflammation occurred via GOLD-induced oxidative stress in mesangial cells. GOLD regulated the mitogen-activated protein kinase (MAPK) and the release of proinflammatory cytokines associated with the inflammatory mechanism of mesangial cells. Furthermore, oxidative stress and inflammatory responses triggered by GOLD were suppressed through RAGE inhibition using RAGE siRNA. These results demonstrate that the interaction of GOLD and RAGE plays an important role in the function of mesangial cells.

Reliability and validity of the Korean version of the Caregiver Burden Inventory.

The purpose of this study was to demonstrate the reliability and validity of the Korean version of the Caregiver Burden Inventory (CBI). The study was conducted as a multicenter cross-sectional survey for caregivers caring for patients with disabilities in outpatient or inpatient rehabilitation clinics. Sociodemographic characteristics and health-related quality of life were collected via questionnaires. The CBI and Burden Interview (BI) were administered, after which internal consistency and factor analysis of the CBI and correlation between the CBI and BI were explored. A total of 151 caregivers participated. The mean age of caregivers was 53.7 ± 12.4 years, and 80.8 % were women. The majority of caregivers were the main caregivers of stroke, spinal cord injury or traumatic brain injury. The factor analysis confirmed its five factorial structure. The time-dependence and physical burden scores of CBI were higher than those of other factors. All five-dimensional and total scores of CBI showed high internal consistency and were well correlated with BI. In conclusion, the CBI has proven its reliability, construct validity and concurrent validity for caregivers of disabled people and has shown its advantage as a multidimensional measure.

Methylglyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Inflammation via Interaction with RAGE in Mesangial Cells.

INTRODUCTION: Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) mediate renal function during diabetic and non-diabetic nephropathy development. Methylglyoxal-lysine dimer (MOLD), a typical toxic advanced glycation end product (TAGE), contributes to inflammatory responses during renal diseases. This study determines the effect of MOLD on inflammatory responses in mouse mesangial cells. METHODS AND RESULTS: The murine mesangial cell line SV40 MES 13 is used to assess nuclear factor-kappa B (NF-κB) expression, reactive oxygen species (ROS) production, and mitochondria labeling. The interaction model between RAGE and MOLD is also determined. MOLD treatment of mesangial cells markedly increases RAGE expression and the linkage with V-type Ig domain of RAGE. MOLD induces ROS production and mitochondrial dysfunction. MOLD activates phosphatidylinositol 3-kinase-protein kinase B (PI3KB) and NF-κB signaling pathways. It is confirmed that these changes are reversed when ROS is suppressed. These effects may be regulated through mitogen-activated protein kinases and pro-inflammatory cytokines in circulatory inflammation responses. CONCLUSION: MOLD plays a major role in nephropathy via ROS production and mitochondrial dysfunction through direct association with RAGE. Further, the NF-kB and PI3K/AKT signaling pathways triggered by ROS mediate the inflammatory response to exacerbate MOLD-induced damages in inflammation-related diabetic and non-diabetic renal diseases.

Hospital adverse outcomes of the elderly in a tertiary referral hospital: A prospective cohort study of 9,586 admissions.

OBJECTIVE: This study aimed to evaluate the hospital adverse outcomes (HAO) of admitted older adult patients in a large prospective cohort and investigate the demographic, economic, and health-related characteristics at risk of HAO in all older adult patients admitted in the general ward of a tertiary referral hospital. MATERIALS AND METHODS: We recruited admission episodes of older adult patients aged over 65 years who were admitted at the general ward of Konkuk University Medical Center, which is a tertiary referral hospital, from September 2016 to October 2017. Out of 9,586 admission episodes, 8,263 were included. Modified from the Geriatric Screening for Care-10, six common geriatric health issues, namely, dysphagia, polypharmacy, fecal incontinence, functional mobility, depression, and dementia, were evaluated. Fall, hospital-acquired pressure ulcer (HPU), and mortality were checked daily by experienced nurses during the patients' hospital stay. A logistic regression model was used, and P < 0.05 was the threshold of significance. RESULTS: The incidence rates of fall and HPU were 1.3 % and 4.0 %, respectively. The hospital mortality was 6.1 %. Older adult patients with dysphagia or dementia upon admission were significantly associated with an increased likelihood of falls. Furthermore, age, ER admission, low income, fecal incontinence, or functional immobility increased the HPU incidence. Meanwhile, age, male, ER admission, fecal incontinence, or functional immobility significantly increased the hospital mortality. CONCLUSION: All demographic, economic, and health-related characteristics, except for polypharmacy and depression, affect the incidence of HAO. Intervention to vulnerable older adult patients with HAO risk could improve the treatment outcome.

How to Improve Patient Safety Literacy?

The aim of this comparative study involving pre- and post-tests was to analyze the effectiveness of patient safety educational materials developed for the Comprehensive Plans for Patient Safety in Korea (2018-2022), and to suggest how to improve patient safety literacy. A face-to-face survey interview comprising items related to general information and patient safety literacy was completed by 217 patients and their families who visited three general hospitals in Seoul and one general hospital in Gyeonggi-do for treatment between 25 October and 15 November 2019. In the interview, the patients were asked questions about whether the patient safety educational materials were "easy to understand," provided "help in safe hospitalization," and enabled patients to practice patient safety independently ("do it yourself"). The literacy of the patient safety educational materials was analyzed using a paired t-test with a p value of 0.05. The comparison between patient safety literacy on pre- and post-tests revealed that among all participants, there were significant differences in "easy to understand," "help in safe hospitalization," and "do it yourself" scores. To improve patient safety literacy, patient education materials need to optimize communication by improving patients' knowledge, skills, and attitudes for maintaining and promoting healthy living.

Importance of Geriatric Syndrome Screening within 48 Hours of Hospitalization for Identifying Readmission Risk: A Retrospective Study in an Acute-Care Hospital.

BACKGROUND: Given the association between geriatric syndrome and hospital readmission, we evaluated the suitability of geriatric syndrome screening for care (GSC) in identifying readmission risk and suggested the appropriate time for GSC. METHODS: GSC considering cognitive impairment, depression, polypharmacy (five or more medications), functional mobility, dysphagia, malnutrition, pain, and incontinence was performed among 2,663 general ward inpatients aged 65 years or older within 48 hours after admission and again before discharge between November 2016 and October 2017. From each patient, fall events, pressure ulcers, potentially inappropriate medication use, and delirium were assessed at admission. Patients were divided into two groups on the basis of readmission within 1 year after the first admission. According to the screening period (at admission and before discharge) and in-hospital decline, we applied receiver operating characteristic curve analysis to compare the prevalence of clinical concerns between the readmission and no-readmission groups. We also used multiple logistic regression analysis to evaluate the risk of readmission according to the presence of geriatric syndrome and clinical outcomes. RESULTS: The 782 readmitted patients (29.4%) showed a higher rate of poor GSC than those who were not readmitted. Polypharmacy at admission was significantly correlated with readmission risk (area under the receiver operating characteristic curve=0.602). Fall events (odds ratio [OR]=4.36; 95% confidence interval [CI], 2.36-8.05), urinary incontinence (OR=4.21; 95% CI, 3.28-5.39), and depressive mood (OR=3.88; 95% CI, 2.69-5.59) at admission were risk factors for readmission. CONCLUSION: Geriatric syndromes assessed by GSC at admission was associated with an increased risk of readmission.

Syzygium aromaticum Reduces Diabetes-induced Glucotoxicity via the NRF2/Glo1 Pathway.

Advanced glycation end products and methylglyoxal are known to show increased levels in diabetic conditions and induce diverse metabolic disorders. However, the antiglycation ability of the bark of Syzygium aromaticum is not yet studied. In this study, we determined the inhibitory effects of S. aromaticum on AGE formation. Moreover, S. aromaticum showed breakage and inhibitory ability against the formation of AGE-collagen crosslinks. In SV40 MES13 cells, treatment with the S. aromaticum extract significantly ameliorated MG-induced oxidative stress as well as cytotoxicity. Furthermore, in the S. aromaticum extract-treated group, there was a reduction in levels of several diabetic markers, such as blood glucose, kidney weight, and urinary albumin to creatinine ratio in streptozotocin-induced diabetic rats. Treatment with the S. aromaticum extract significantly increased the expression of nuclear factor erythroid 2-related factor 2, a transcription factor involved in the expression of antioxidant enzymes. Moreover, the treatment significantly upregulated the expression of glyoxalase 1 and downregulated the expression of receptor for AGEs. These results suggest that the S. aromaticum extract might ameliorate diabetes-induced renal damage by inhibiting the AGE-induced glucotoxicity and oxidative stress through the Nrf2/Glo1 pathway.

Characterization of macrophage stimulating compound in glycated whey protein concentrate.

Whey, a by-product of cheese making, is a collection of several milk proteins and has functional and nutritional values. Whey protein concentrate (WPC) exhibits various functional effects by glycation. Studies to find sugar-binding sites in a protein having a functional effect are reported. However, it is rarely clear whether it confirms that glycated single protein exhibits the same effect of protein cluster. This study confirmed which protein sites are responsible for the effect of glycated WPC (G-WPC). ß-Lactoglobulin (LG) was the major protein of G-WPC and glycated with lactose. The glycated LG increased the nitric oxide and cytokine secretion similar to G-WPC and peptide sequences of active compound was confirmed using the high molecular weight band of G-WPC. The K151 and K157 residues of LG were modified by glycation with sugar in common with G-WPC. These residues of glycated LG potentially contribute to the immune-modulation effect of G-WPC.

Autophagy Functions to Prevent Methylglyoxal-Induced Apoptosis in HK-2 Cells.

Methylglyoxal (MGO), a reactive carbonyl species, causes cellular damage and is closely related to kidney disease, particularly diabetic nephropathy. Although MGO has been reported to induce autophagy and apoptosis, the relationships between the two pathways are unclear. Here, we evaluated whether autophagy may be the underlying mechanism inhibiting MGO-induced apoptosis. MGO treatment induced concentration- and time-dependent apoptosis in HK-2 cells. Moreover, MGO upregulated the autophagy markers p62 and LC3-II. Apoptosis caused by MGO was increased in ATG5-knockdown cells compared to that in wild-type cells. In contrast, autophagy activation by 5-aminoimidazole-4-carboxamide ribonucleotide resulted in reduced apoptosis, suggesting that autophagy played a role in protecting against MGO-induced cell death. To examine the mechanisms through which autophagy occurred following MGO stimulation, we investigated changes in AKT/mammalian target of rapamycin (mTOR) signaling. Autophagy induction by MGO treatment was not related to AKT/mTOR signaling; however, it did involve autophagy-related gene expression promoted by AMP-activated protein kinase-mediated transcription factors, such as forkhead box 1. Overall, our findings indicate that MGO-induced cellular damage can be mitigated by autophagy, suggesting that autophagy may be a potential therapeutic target for diseases such as diabetic nephropathy.