Caffeine inhibits hypoxia-induced renal fibroblast activation by antioxidant mechanism

Nilnumkhum, Angkhana; Kanlaya, Rattiyaporn; Yoodee, Sunisa; Thongboonkerd, Visith

doi:10.1080/19336918.2019.1638691

Cited by 28 publications

(24 citation statements)

References 56 publications

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“…Hence, SSAO inhibition aids patients with diabetes to decrease the levels of toxic compounds. Caffeine is a natural substance with antioxidant capacity commonly consumed worldwide in daily life [ 77 , 78 ]. It has the ability of inhibiting SSAO as it contains an imidazole ring [ 68 , 79 ].…”

Section: Promising Agents Involved In Regulating Semicarbazide-senmentioning

confidence: 99%

Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus

2020

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Creatine supplementation of the population with type 2 diabetes mellitus (T2DM) combined with an exercise program is known to be a possible therapy adjuvant with hypoglycemic effects. However, excessive administration of creatine leads to the production of methylamine which is deaminated by the enzyme semicarbazide-sensitive amine oxidase (SSAO) and as a result, cytotoxic compounds are produced. SSAO activity and reaction products are increased in the serum of T2DM patients. Creatine supplementation by diabetics will further augment the activity of SSAO. The current review aims to find a feasible way to ameliorate T2DM for patients who exercise and desire to consume creatine. Several natural agents present in food which are involved in the regulation of SSAO activity directly or indirectly are reviewed. Particularly, zinc-α2-glycoprotein (ZAG), zinc (Zn), copper (Cu), histamine/histidine, caffeine, iron (Fe), and vitamin D are discussed. Inhibiting SSAO activity by natural agents might reduce the potential adverse effects of creatine metabolism in population of T2DM.

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Section: Promising Agents Involved In Regulating Semicarbazide-senmentioning

confidence: 99%

Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus

2020

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“…For example, caffeine prevented acute ROS-induced necrosis in human skin fibroblasts and inhibited oxidative stress-induced aging by activating autophagy (Li et al, 2018). Additionally, caffeine was found to reduce oxidative stress by antioxidant mechanism (Badshah et al, 2019;Nilnumkhum et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Caffeine Targets SIRT3 to Enhance SOD2 Activity in Mitochondria

Gan

Gao

et al. 2020

Front. Cell Dev. Biol.

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Caffeine is chemically stable and not readily oxidized under normal physiological conditions but also has antioxidant effects, although the underlying molecular mechanism is not well understood. Superoxide dismutase (SOD) 2 is a manganesecontaining enzyme located in mitochondria that protects cells against oxidative stress by scavenging reactive oxygen species (ROS). SOD2 activity is inhibited through acetylation under conditions of stress such as exposure to ultraviolet (UV) radiation. Sirtuin 3 (SIRT3) is the major mitochondrial nicotinamide adenine dinucleotide (NAD +)-dependent deacetylase, which deacetylates two critical lysine residues (lysine 68 and lysine 122) on SOD2 and promotes its antioxidative activity. In this study, we investigated whether the antioxidant effect of caffeine involves modulation of SOD2 by SIRT3 using in vitro and in vivo models. The results show that caffeine interacts with SIRT3 and promotes direct binding of SIRT3 with its substrate, thereby enhancing its enzymatic activity. Mechanistically, caffeine bound to SIRT3 with high affinity (K D = 6.858 × 10 −7 M); the binding affinity between SIRT3 and its substrate acetylated p53 was also 9.03 (without NAD +) or 6.87 (with NAD +) times higher in the presence of caffeine. Caffeine effectively protected skin cells from UV irradiation-induced oxidative stress. More importantly, caffeine enhanced SIRT3 activity and reduced SOD2 acetylation, thereby leading to increased SOD2 activity, which could be reversed by treatment with the SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) in vitro and in vivo. Taken together, our results show that caffeine targets SIRT3 to enhance SOD2 activity and protect skin cells from UV irradiation-induced oxidative stress. Thus, caffeine, as a small-molecule SIRT3 activator, could be a potential agent to protect human skin against UV radiation.

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“…Glomeruli have not any stain in all sections of all study groups. ROS mediated by both ASP and caffeine products, increase lipolysis, renal ischemia and pro‐inflammatory cells; all are predisposing factors for occurring of renal fibrosis and so of collagen and high alpha‐smooth muscles deposition (Nilnumkhum, Kanlaya, Yoodee, & Thongboonkerd, 2019).…”

Section: Discussionmentioning

confidence: 99%

Could aspartame exacerbate caffeine effects on renal maturation in rat's offspring? A biochemical and histological study

Fareed

Mostafa

2020

Birth Defects Research

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Background Caffeine and aspartame (ASP) are mostly used as a diet regimen to reduce overweight. The risk increase if used during critical life periods that may affect the development of fetal organs. Objective To evaluate the individual and combined effects of maternal exposure to caffeine and ASP during gestation and lactation on the kidneys' development of rats' offspring. Methods Pregnant rats were divided randomly into four groups; Group I (control group). Group II (ASP group): ASP was given at a dose of 40 mg of /kg/day. Group III (Caffeine group): caffeine was given at a dose of 80 mg/kg/day. Group IV (ASP & caffeine group); where previous doses of ASP and caffeine were given at the same time. All the treatments were given by oral gavage from the first day of pregnancy until postnatal day 30. Kidneys of rats' offspring were dissected and tested for detection of oxidative stress markers and for histopathological & immunohistochemical examination. Results This study showed a high significant increase in oxidative load (malondialdehyde) in renal tissues in group IV associated with decreased activities of total glutathione and antioxidant enzymes (superoxide dismutase and glutathione peroxidase). Histological and morphometric examination results showed delayed maturation of renal tissues in Group II and III, but more deleterious effects were observed in group IV with a lot of pathological changes in renal tissues. Conclusion The extensive use of caffeine and ASP should be controlled to avoid the risk of their toxicity.

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Caffeine inhibits hypoxia-induced renal fibroblast activation by antioxidant mechanism

Cited by 28 publications

References 56 publications

Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus

Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus

Caffeine Targets SIRT3 to Enhance SOD2 Activity in Mitochondria

Could aspartame exacerbate caffeine effects on renal maturation in rat's offspring? A biochemical and histological study

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