Shen-Kang protects against tacrolimus-induced renal injury

Zhang, Long Ye; Jin, Jian; Luo, Kun; Piao, Shang Guo; Zheng, Hongliang; Jin, Ji Zhe; Lim, Sun Woo; Choi, Bum Soon; Yang, Chul Woo; Li, Can

doi:10.3904/kjim.2017.276

Cited by 11 publications

(8 citation statements)

References 29 publications

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“…However, chronic TAC nephropathy caused by the long-term use of TAC is a major cause of late graft failure in KT recipients [ 16 ]. Therefore, researchers are interested in reducing nephrotoxicity, and several trials have been conducted to inhibit the various pathophysiologic pathways involved in TAC-induced nephrotoxicity [ 3 , 17 , 18 ]. We have focused on the effects of AAT on renal fibrosis, inflammation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, OPN binds strongly to macrophages, resulting in prominent macrophage infiltration [ 40 , 41 ]. In the in vitro and in vivo TAC nephropathy studies, tubular OPN expression was avidly associated with macrophage infiltration and subsequent tubulointerstitial injury [ 3 , 42 ]. Our results were also consistent with these findings; OPN was overexpressed in the TAC group, notably in the inflammatory areas.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, the TAC-based immunosuppressive regimen is the globally preferred treatment in kidney transplant (KT) recipients [ 1 , 2 ]. However, despite the effective immunosuppressive property, long-term TAC treatment causes irreversible kidney injury and adversely affects long-term graft survival [ 3 ]. The histopathologic features of TAC-induced renal injury are arteriolar hyalinization, vasoconstriction, interstitial fibrosis (IF), tubular atrophy, and apoptosis [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Lim

et al. 2020

IJMS

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The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal injections of AAT (80 mg/kg) for four weeks. The effects of AAT on TAC-induced renal injury were evaluated using serum biochemistry, histopathology, and Western blotting. The TAC injection significantly increased renal interstitial fibrosis, inflammation, and apoptosis as compared to the control treatment. The histopathological examination showed that cotreatment of TAC and AAT attenuated interstitial fibrosis (collagen, fibronectin, and α-SMA staining), and α-SMA expression in Western blotting was also decreased. Immunohistochemical staining for inflammation (osteopontin and ED-1 staining) revealed improved interstitial inflammation in the TAC with AAT group compared to that in the TAC group. The TAC treatment increased renal apoptosis compared to the control treatment, based on the results of increased immunohistochemical staining of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), increased caspase-3 activity, and lower Bcl-2 to Bad expression ratio. However, AAT cotreatment significantly changed these markers and consequently showed decreased apoptosis. AAT protects against TAC-induced renal injury via antifibrotic, anti-inflammatory, and antiapoptotic effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Lim

et al. 2020

IJMS

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“…Following a 1-week acclimatization period on a low-salt diet, weight-matched rats were randomized into four subgroups and treated daily for 4 weeks with: (1) subcutaneous injection with olive oil (vehicle [VH] group, n = 8, 1 mL/kg); (2) simultaneous treatment with olive oil and NIC (NIC group, n = 8, 1.5 mg/kg; intraperitoneal, n = 8); (3) subcutaneous injection with TAC (TAC group, n = 8, 1.5 mg/kg); (4) simultaneous treatment with a combination of NIC and TAC (NIC + TAC group, n = 8). TAC (Prograf, Astellas Pharma, Ibaraki, Japan) and NIC (Sigma-Aldrich) doses were based on previous studies [ 9 , 10 ].…”

Section: Methodsmentioning

confidence: 99%

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

Jiang

Sheng

Luo

et al. 2021

Korean J Intern Med

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Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury.Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy).Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined.Conclusions: Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

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“…These include TAC-induced DM, which is an important adverse effect in organ transplant recipients [ 2 , 3 ]. The mechanisms of TAC-induced DM are not well studied, but direct injury to pancreatic islet cells or impaired insulin signaling by TAC are regarded as the main pathogenesis methods, and oxidative stress plays a significant role in the process of TAC-induced pancreatic islet injury [ 4 , 5 ]. Thus, reducing TAC-induced oxidative stress is one of the important approaches for decreasing TAC-induced DM.…”

Section: Introductionmentioning

confidence: 99%

The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

Quan

Luo

Sheng

et al. 2020

Korean J Intern Med

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Background/Aims: Coenzyme Q 10 (CoQ 10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ 10-based micelle formulation (CoQ 10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). Methods: We developed CoQ 10-W from a glycyrrhizic-carnitine mixed layer CoQ 10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ 10 (CoQ 10-L) or CoQ 10-W for 4 weeks. Their plasma and pancreatic CoQ 10 concentrations were measured using liquid chromatography-tandem mass spectrometry. The therapeutic efficacies of CoQ 10-W and CoQ 10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. Results: The plasma CoQ 10 level was signif icantly increased in the CoQ 10-W group compared to that in the CoQ 10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ 10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ 10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ 10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ 10-W than CoQ 10-L. Electron microscopy revealed that CoQ 10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ 10-L. In vitro studies showed that CoQ 10-L and CoQ 10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. Conclusions: CoQ 10-W has better therapeutic efficacy than CoQ 10-L in TAC-induced DM.

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Shen-Kang protects against tacrolimus-induced renal injury

Abstract: SK protects against TAC-induced renal injury.

Cited by 11 publications

References 29 publications

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury

Nicotine exacerbates tacrolimus-induced renal injury by programmed cell death

The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

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