Regulation of Glutathione in Health and Disease with Special Emphasis on Chronic Alcoholism and Hyperglycaemia Mediated Liver Injury: A Brief Perspective

Kumar, Santosh; Dey, Aparajita

doi:10.1007/s40362-013-0015-6

Cited by 8 publications

(4 citation statements)

References 124 publications

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“…Diethyl maleate (DEM) is a known GSH-decreasing agent and was used to induce GSH-deficient conditions in M. tb infected mice [14]. GSH diminishment is achieved through enzymatic conjugation of DEM to GSH via a thioester bond, inactivating GSH activity [20,21]. The results of our in vivo studies indicate that DEM treatment exacerbated the inflammatory response, leading to a redox imbalance and thereby increasing the burden of M. tb in the lungs and spleen of the mice.…”

Section: Introductionmentioning

confidence: 86%

Effects of Glutathione Diminishment on the Immune Responses against Mycobacterium tuberculosis Infection

et al. 2021

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Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), continues to be a global health burden. We have reported that patients with marked deficiency in the production of glutathione (GSH) had impaired granulomatous effector responses against M. tb infection, which were restored when supplementing patients with liposomal GSH (lGSH). However, the effects of GSH deficiency in the lung parenchyma in altering granuloma formation and effector responses against M. tb infection remain unexplored. We aim to elucidate the effects of diethyl maleate (DEM)-induced GSH deficiency during an active M. tb infection in an in vivo mouse model. We assessed for total and reduced GSH levels, malondialdehyde (MDA) levels, cytokine profiles, granuloma formation and M. tb burden. DEM administration significantly diminished total and reduced GSH levels in the lungs and plasma and increased MDA levels in infected mice compared to sham-treated controls. DEM treatment was also associated with an increase in IL-6, TNF-α and ill-formed granulomas in infected mice. Furthermore, M. tb survival was significantly increased along with a higher pulmonary and extrapulmonary bacterial load following DEM treatment. Overall, GSH deficiency led to increased oxidative stress, impaired granuloma response, and increased M. tb survival in infected mice. These findings can provide insight into how GSH deficiency can interfere with the control of M. tb infection and avenues for novel therapeutic approaches.

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Section: Introductionmentioning

confidence: 86%

Effects of Glutathione Diminishment on the Immune Responses against Mycobacterium tuberculosis Infection

et al. 2021

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“…Therefore, BSO is expected to impair GSH production (49). DEM is an electrophilic reagent that forms conjugates with GSH through the catalytic action of GSH transferase, leading to a rapid GSH depletion (50–52). Given these two compounds can abolish the protection phenotypes, we assessed GSH levels following NINJ1 knockdown.…”

Section: Resultsmentioning

confidence: 99%

NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation

Chen,

Lin,

et al. 2024

Preprint

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Ninjurin-1 (NINJ1), initially identified as a stress-induced protein in neurons, recently emerged as a key mediator of plasma membrane rupture during apoptosis, necrosis, and pyroptosis. However, its involvement in ferroptosis remains unknown. Here, we demonstrate that NINJ1 also plays a crucial role in ferroptosis, but through a distinct mechanism. NINJ1 knockdown significantly protected cancer cells against ferroptosis induced by xCT inhibitors but no other classes of ferroptosis-inducing compounds (FINs). Glycine, known to inhibit canonical NINJ1-mediated membrane rupture in other cell deaths, had no impact on ferroptosis. A compound screen revealed that NINJ1-mediated ferroptosis protection can be abolished by pantothenate kinase inhibitor (PANKi), buthionine sulfoximine (BSO), and diethylmaleate (DEM). These results suggest that this ferroptosis protection is mediated via Coenzyme A (CoA) and glutathione (GSH), both of which were found to be elevated upon NINJ1 knockdown. Furthermore, we discovered that NINJ1 interacts with the xCT antiporter, which is responsible for cystine uptake for the biosynthesis of CoA and GSH. The removal of NINJ1 increased xCT levels and stability, enhanced cystine uptake, and contributed to elevated CoA and GSH levels, collectively contributing to ferroptosis protection. These findings reveal that NINJ1 regulates ferroptosis via a non-canonical mechanism, distinct from other regulated cell deaths.

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“…In the present study, the reduced GSH levels in untreated Chang liver cells ( Figure 3 ) implied the occurrence of oxidative stress, as reduced GSH levels have been regarded as an oxidative stress marker at the cellular level [ 20 ]. Elevated cellular levels of GSH significantly reduce oxidative stress and cellular toxicity [ 21 ]. Thus, the increased level of GSH in cells pretreated with C. gratissimus ( Figure 3 ) may suggest the hepatoprotective property of the herbal tea.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury

Ncume,

Salau,

Mtshali

et al. 2023

Plants

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Oxidative stress plays a vital role in the pathogenesis and progression of various liver diseases. Traditional medicinal herbs have been used worldwide for the treatment of chronic liver diseases due to their high phytochemical constituents. The present study investigated the phytochemical properties of Croton gratissimus (lavender croton) leaf herbal tea and its hepatoprotective effect on oxidative injury in Chang liver cells, using an in vitro and in silico approach. C. gratissimus herbal infusion was screened for total phenolic and total flavonoid contents as well as in vitro antioxidant capacity using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) methods. Oxidative hepatic injury was induced by incubating 0.007 M FeSO4 with Chang liver cells which has been initially incubated with or without different concentrations (15–240 μg/mL) of C. gratissimus infusion or the standard antioxidants (Gallic acid and ascorbic acid). C. gratissimus displayed significantly high scavenging activity and ferric reducing capacity following DPPH and FRAP assays, respectively. It had no cytotoxic effect on Chang liver cells. C. gratissimus also significantly elevated the level of hepatic reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities as well as suppressed the malondialdehyde (MDA) level in oxidative hepatic injury. Liquid Chromatography–Mass Spectrometry (LC-MS) analysis of the herbal tea revealed the presence of 8-prenylnaringenin, flavonol 3-O-D-galactoside, caffeine, spirasine I, hypericin, pheophorbide-a, and 4-methylumbelliferone glucuronide. In silico oral toxicity prediction of the identified phytochemicals revealed no potential hepatotoxicity. Molecular docking revealed potent molecular interactions of the phytochemicals with SOD and catalase. The results suggest the hepatoprotective and antioxidative potentials of C. gratissimus herbal tea against oxidative hepatic injury.

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Regulation of Glutathione in Health and Disease with Special Emphasis on Chronic Alcoholism and Hyperglycaemia Mediated Liver Injury: A Brief Perspective

Cited by 8 publications

References 124 publications

Effects of Glutathione Diminishment on the Immune Responses against Mycobacterium tuberculosis Infection

Effects of Glutathione Diminishment on the Immune Responses against Mycobacterium tuberculosis Infection

NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury

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