SIRT1 inhibitors mitigate radiation-induced GI syndrome by enhancing intestinal-stem-cell survival

Fu, Guoxiang; Chen, Shengzhi; Liang, Li‐Ping; Li, Yongming; Tang, Peiyuan; Rao, Xinxin; Pan, Mengxue; Xu, Xiang; Li, Yuanchuang; Yao, Ye; Zhou, Yi; Gao, Jun; Mo, Shaobo; Cai, Sanjun; Peng, Junjie; Zhang, Zhen; Gao, Jianjun; Hua, Guoqiang

doi:10.1016/j.canlet.2020.12.034

Cited by 28 publications

(16 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, epithelial injury is the primary result of IR-induced elimination of ISCs residing at the bottom of the crypt [34]. High-proliferating and radiosensitive Lgr5 + ISCs can generate all types of mature intestinal epithelial cells in vitro and in vivo [35,36] and are indispensable for radiation-induced intestinal regeneration [19,37]. In this study, PAH-mediated radioprotection was closely associated with the number of Lgr5 + ISCs in the intestine after irradiation.…”

Section: Discussionmentioning

confidence: 69%

Perillaldehyde mitigates ionizing radiation-induced intestinal injury by inhibiting ferroptosis via the Nrf2 signaling pathway

Tang¹,

Xie

Zhou³

et al. 2023

Preprint

View full text Add to dashboard Cite

The gastrointestinal tract is a rapidly self-renewing system and is thus highly sensitive to ionizing radiation (IR). Unfortunately, methods for preventing and treating IR-induced gastrointestinal syndrome are limited. Volatile monoterpenoid perillaldehyde (PAH) is the major component of the essential oil extracted from perilla plants and has been demonstrated to have antioxidant, anti-inflammatory, antimicrobial activity, and antitumor effects. However, its role in preventing or alleviating radiation-induced injuries remains unknown. In this study, PAH prolonged the survival time and attenuated radiation-induced intestinal injury in whole abdominal lethally irradiated mice. PAH treatment also promoted the survival of crypt cells, attenuated radiation-induced DNA damage, and mitigated intestinal barrier damage in irradiated mice. The radioprotective effects of PAH in intestinal crypt organoids and human intestinal epithelial cell line (HIEC-6) were also identified. PAH-mediated radioprotection was associated with the upregulation of Nrf2, activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolished the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity. The findings of this study collectively suggest that PAH is a promising therapeutic strategy for IR-induced intestinal injury.

show abstract

Section: Discussionmentioning

confidence: 69%

Perillaldehyde mitigates ionizing radiation-induced intestinal injury by inhibiting ferroptosis via the Nrf2 signaling pathway

Tang¹,

Xie

Zhou³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Notably, NAM can be used as a direct substrate for NAMPT to generate NAD+ 21 . To date, several studies demonstrated the effect of NAM on ameliorating radiation damage in human lymphocytes, human keratinocytes, mouse liver, mouse taste bud stem cells, and mouse intestinal stem cells 15,22–25 . However, it is still unknown whether NAM could prevent radiation damage in salivary gland.…”

Section: Discussionmentioning

confidence: 99%

“…*p < 0.05 versus the controls; #p < 0.05 versus the irradiation alone. NAD, nicotinamide adenine dinucleotide; NADH, reduced nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyl transferase; SMG, submandibular gland keratinocytes, mouse liver, mouse taste bud stem cells, and mouse intestinal stem cells 15,[22][23][24][25]. However, it is still unknown whether NAM could prevent radiation damage in salivary gland.…”

mentioning

confidence: 99%

Nicotinamide mitigates radiation injury in submandibular gland by protecting mitochondrial structure and functions

Wang

Liu

Zhang

et al. 2022

J Oral Pathology Medicine

View full text Add to dashboard Cite

Background: Radiation damage to salivary gland is inevitable in head and neck cancer patients receiving radiotherapy. Safe and effective treatments for protecting salivary glands from radiation are still unavailable. Mitochondrial damage is a critical mechanism in irradiated salivary gland; however, treatment targeting mitochondria has not received much attention. Nicotinamide is a key component of the mitochondrial metabolism. Here, we investigated the effects and underlying mechanisms of nicotinamide on protecting irradiated submandibular gland. Methods: Submandibular gland cells and tissues were randomly divided into four groups: control, nicotinamide alone, radiation alone, and radiation with nicotinamide pretreatment. Cell viability was detected by PrestoBlue cell viability reagent. Histopathological alterations were observed with HE staining. Pilocarpine-stimulated saliva was measured from Wharton's duct. Cell apoptosis was determined by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Nicotinamide phosphoribosyl transferase was examined with immunofluorescence. The levels of nicotinamide adenine dinucleotide, mitochondrial membrane potential, and adenosine triphosphate were measured with the relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy.Results: Nicotinamide significantly mitigated radiation damage both in vitro and in vivo. Also, nicotinamide improved saliva secretion and reduced radiation-induced apoptosis in irradiated submandibular glands. Moreover, nicotinamide improved nicotinamide phosphoribosyl transferase and the levels of nicotinamide adenine dinucleotide/adenosine triphosphate and mitochondrial membrane potential, all of which were decreased by radiation in submandibular gland cells. Importantly, nicotinamide protected the mitochondrial ultrastructure from radiation. Conclusion:These findings demonstrate that nicotinamide alleviates radiation damage in submandibular gland by replenishing nicotinamide adenine dinucleotide and maintaining mitochondrial function and ultrastructure, suggesting that nicotinamide could be used as a prospective radioprotectant for preventing radiation sialadenitis.

show abstract

“…PDO models of CRC. Organoids were established as described previously by D1Med Technology Inc. (61,62). In this study, 50 organoids/well were laid into 48-well plates and incubated in 5% CO 2 /95% air at 37°C for total 6 days.…”

Section: Methodsmentioning

confidence: 99%

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

Jin¹,

Wu²,

Zhao³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

SIRT1 inhibitors mitigate radiation-induced GI syndrome by enhancing intestinal-stem-cell survival

Cited by 28 publications

References 35 publications

Perillaldehyde mitigates ionizing radiation-induced intestinal injury by inhibiting ferroptosis via the Nrf2 signaling pathway

Perillaldehyde mitigates ionizing radiation-induced intestinal injury by inhibiting ferroptosis via the Nrf2 signaling pathway

Nicotinamide mitigates radiation injury in submandibular gland by protecting mitochondrial structure and functions

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

Contact Info

Product

Resources

About