Curcumin ameliorates cisplatin‐induced cystopathy via activating NRF2 pathway

Shao, Yun; Zhou, Qiao; Li, Yun Peng; Zhang, Si Cong; Xu, He; Wu, Shuo; Shen, Baixin; Ding, Liu Cheng; Xue, Jun; Chen, Zheng Sen; Wei, Zhong Qing

doi:10.1002/nau.23731

Cited by 13 publications

(6 citation statements)

References 24 publications

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“…Cisplatin is an effective anticancer drug, but it has demonstrated toxicity to the bladder [15], inner ear [16], peripheral nerves [17], and reproductive system [15]. Melatonin is capable of attenuating testis toxicity induced by microwave radiation [18], 2-bromopropane [19], and busulfan [20]; thus, melatonin may be useful in preventing the effect of cisplatininduced toxicity on fertility.…”

Section: Discussionmentioning

confidence: 99%

“…1a). Then, a working concentration of 250 µM cisplatin was selected, on the basis of a previous report [15], for use in combination with human sperm and different concentrations of melatonin. Our experimental results showed that only 100 mM melatonin could restore cisplatin-induced sperm dysfunction, and 5, 12.5, and 50 mM melatonin could not recover either total motility or progressive motility (Fig.…”

Section: Melatonin Significantly Restored Human Sperm Motilitymentioning

confidence: 99%

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Melatonin ameliorates cisplatin-induced asthenozoospermia via reducing oxidative stress

Shao¹,

Zhou²,

Xue³

et al. 2021

JOMH

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Background and objective:Cisplatin is an alkylating agent that has become a first-line therapy for some tumors. However, overproduction of reactive oxygen species (ROS) by cisplatin can cause male infertility, which can affect patients' quality of life. Melatonin, which has the ability to provide resistance against oxidation, is a potential therapy for male infertility caused by cisplatin.Material and methods: Normal human spermatozoa samples were divided into (i) control group incubated with physiological saline solution; (ii) cisplatin group incubated with cisplatin; (iii) melatonin group incubated with melatonin; and (iv) melatonin + cisplatin group incubated with melatonin and cisplatin. Spermatozoa motility was measured using a computer-aided semen analysis system.Additionally, we determined spermatozoa apoptosis through terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling. The mitochondrial membrane potential (∆Ψm) and levels of ATP, ROS, and malondialdehyde, as a metabolite of oxidative stress, were measured to study the mechanism by which melatonin can protect human spermatozoa. Results: Melatonin improved sperm motility, and decreased apoptosis and increased the ∆Ψm value and level of ATP in sperm. More importantly, the overproduction of ROS induced by cisplatin was reduced by melatonin. Furthermore, western blotting revealed that melatonin increased the expression of antioxidant pathway components nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) that was reduced by cisplatin. Conclusion:Our studies suggested that melatonin might protect human spermatozoa against the effects of cisplatin through Nrf2/HO-1.

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Section: Discussionmentioning

confidence: 99%

Section: Melatonin Significantly Restored Human Sperm Motilitymentioning

confidence: 99%

Melatonin ameliorates cisplatin-induced asthenozoospermia via reducing oxidative stress

Shao¹,

Zhou²,

Xue³

et al. 2021

JOMH

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“… [ 66 ] Cisplatin-Induced Bladder Cystopathy Female SD rats 6 mg/kg, 5 consecutive days RBSMCs, SV-HUC-1, ATCC, Manassas, VA NGF, HO-1 CUR via targeting NRF2 could ameliorate cisplatin-induced cystopathy. [ 67 ] Pain Male Swiss mice 3, 10, 30 mg/kg, subcutaneously, 1 h before stimulation - NF-ĸB, HO-1, TNF-α, IL-10, IL-1β CUR via reducing NF-κB activation and increasing Nrf2 expression could inhibit superoxide anion-induced inflammatory pain-like behaviors. [ 68 ] Endotoxemia Male Wistar rats 25,50, and 100 mg/kg, orally, 2 consecutive days - TNF-α, IL1-β CUR via modulating the activity of Nrf2 could prevent LPS-induced sickness behavior and fever possibly.…”

Section: Other Conditionsmentioning

confidence: 99%

Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders

et al. 2022

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Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.

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“…Curcumin’s antioxidative effects on bladder function are dependent on the promotion of the Nrf2 HO-1 pathway. It limited apoptotic enzymes, supported NGF protein synthesis and applied neurorestorative impacts on the urinary bladder in cisplatin-induced bladder injury in rats [ 94 ].…”

Section: Nrf2 Is An Essential Factor For Curcumin Effects On the Cellular Processes And Enzymesmentioning

confidence: 99%

Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects

et al. 2021

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Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc–curcumin Zn (II)–curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc–curcumin Zn (II)–curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.

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Curcumin ameliorates cisplatin‐induced cystopathy via activating NRF2 pathway

Cited by 13 publications

References 24 publications

Melatonin ameliorates cisplatin-induced asthenozoospermia via reducing oxidative stress

Melatonin ameliorates cisplatin-induced asthenozoospermia via reducing oxidative stress

Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders

Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects

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