Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats

Hamed, Moses Agbomhere; Akhigbe, T. M.; Akhigbe, R.E.; Aremu, Adeyemi Oladapo; Oyedokun, P A; Gbadamosi, Jibriil A; Anifowose, P.E.; Adewale, Musa Abdus-Semiu; Aboyeji, O.O.; Yisau, H.O.; Tajudeen, G.O.; Titiloye, M.M.; Ayinla, N.F.; Ajayi, Ayodeji Folorunsho

doi:10.1016/j.biopha.2022.112765

Cited by 30 publications

(24 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zebrafish are often used as biological models for in vivo studies of small molecules and drugs because of their fast growth rate, small size, transparency, and ease of handling ( 77 , 78 ). Glutathione, as a key antioxidant element, with the formation of its disulfide dimer, can respond to chemical stress and clear ROS, thereby balancing the intracellular redox homeostasis, helping to prevent oxidative stress in cells, and maintain a normal immune system ( 74 , 79 ). The intensity of green fluorescence is positively correlated with the level of ROS, and the higher the brightness, the higher the level of ROS.…”

Section: Resultsmentioning

confidence: 99%

Extraction, isolation, structural characterization, and antioxidant activity of polysaccharides from elderberry fruit

et al. 2022

View full text Add to dashboard Cite

The isolation, purification, and antioxidant activity of polysaccharides extracted from elderberry fruits were studied. Two neutral polysaccharides (EFP-0 and EFP-1) and three acidic polysaccharides (EFP-2, EFP-3, and EFP-4) were isolated from elderberry. EFP-0, EFP-1, EFP-2, EFP-3, and EFP-4 all contain arabinose, galactose, glucose, and mannose, with molecular weights of 1.7981 × 106, 7.0523 × 106, 7.7638 × 106, 4.3855 × 105, and 7.3173 × 105 Da, respectively. Structural characterization showed that the backbone of EFP-2 consisted of →4)-Manp (1→4)-β-D-Glcp (1→ and →4)-β-D-Glcp (1→5)-α-L-Araf (1→units, and T-α-L-Araf (1→ and T-β-D-Galp (1→ residues were detected by methylation analysis and NMR analysis. In addition, the MTT assay and zebrafish oxidative damage assay showed that EFP-2 had a protective effect on H2O2-damaged RAW264.7 cells in a dose-dependent manner, and zebrafish with the addition of EFP-2 would have low levels of ROS in vivo which showed significant antioxidant activity. Therefore, the results showed that the elderberry polysaccharides have antioxidant activity and can be used as potential antioxidants in functional foods.

show abstract

Section: Resultsmentioning

confidence: 99%

Extraction, isolation, structural characterization, and antioxidant activity of polysaccharides from elderberry fruit

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The preservation of cellular antioxidants that was associated with preserved intestinal and hepatic cytoarchitecture in MMOLE-treated rats suggests that the botanical conferred cellular protection in IIRI. Cellular antioxidants are integral parts of tissues that protect the cell against ROS-mediated oxidative injury (Hamed et al, 2022). SOD converts superoxide radicals into dioxygen and hydrogen peroxide, which is further broken down into water and molecular oxygen by catalase (Akhigbe et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress has been established as a cause and/or consequence of inflammation. Oxidative stress triggers the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) to the nucleus and induces the transcription of several deleterious pro-inflammatory genes (Won et al, 2006;Hamed et al, 2022). In addition, oxidative stress upregulates pro-inflammatory cytokines such as TNF-α and IL-6 that in turn activate NF-kB (Akhigbe and Ajayi, 2020;Hamed et al, 2022), prime neutrophil infiltration (Sheppard et al, 2005), and promote ROS-induced oxidative stress (Akhigbe and Ajayi, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…The intestinal and hepatic concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) , and the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) (Hamed et al, 2021;Hamed et al, 2022) in the intestinal and hepatic tissues were assayed by spectrophotometry as previously reported. Thiol and non-thiol proteins were assayed by colorimetry as earlier reported (Jocelyn, 1987;Hu, 1994).…”

Section: Markers Of Oxidative Stress and Antioxidant Levelsmentioning

confidence: 99%

See 1 more Smart Citation

Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3

Afolabi

Akhigbe

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI.Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS.Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3.Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid.

show abstract

“…Of note, L-glutamine, one of the 3 recently FDA-approved treatments for SCD (L-glutamine, crizanlizumab, and voxelotor), increases glutathione-dependent anti-oxidation in the testis and testosterone levels, at least in sleep-deprived rats ( 85 ), while alleviating primary hypogonadism and protecting erythrocytes against oxidative damage.…”

Section: Endogenous Mechanism-specific Molecular Targets For Testoste...mentioning

confidence: 99%

Testosterone Deficiency in Sickle Cell Disease: Recognition and Remediation

Musicki¹,

Burnett²

2022

Front. Endocrinol.

View full text Add to dashboard Cite

Hypogonadism is common in men with sickle cell disease (SCD) with prevalence rates as high as 25%. Testicular failure (primary hypogonadism) is established as the principal cause for this hormonal abnormality, although secondary hypogonadism and compensated hypogonadism have also been observed. The underlying mechanism for primary hypogonadism was elucidated in a mouse model of SCD, and involves increased NADPH oxidase-derived oxidative stress in the testis, which reduces protein expression of a steroidogenic acute regulatory protein and cholesterol transport to the mitochondria in Leydig cells. In all men including those with SCD, hypogonadism affects physical growth and development, cognition and mental health, sexual function, as well as fertility. However, it is not understood whether declines in physical, psychological, and social domains of health in SCD patients are related to low testosterone, or are consequences of other abnormalities of SCD. Priapism is one of only a few complications of SCD that has been studied in the context of hypogonadism. In this pathologic condition of prolonged penile erection in the absence of sexual excitement or stimulation, hypogonadism exacerbates already impaired endothelial nitric oxide synthase/cGMP/phosphodiesterase-5 molecular signaling in the penis. While exogenous testosterone alleviates priapism, it disadvantageously decreases intratesticular testosterone production. In contrast to treatment with exogenous testosterone, a novel approach is to target the mechanisms of testosterone deficiency in the SCD testis to drive endogenous testosterone production, which potentially decreases further oxidative stress and damage in the testis, and preserves sperm quality. Stimulation of translocator protein within the transduceosome of the testis of SCD mice reverses both hypogonadism and priapism, without affecting intratesticular testosterone production and consequently fertility. Ongoing research is needed to define and develop therapies that restore endogenous testosterone production in a physiologic, mechanism-specific fashion without affecting fertility in SCD men.

show abstract

Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats

Cited by 30 publications

References 62 publications

Extraction, isolation, structural characterization, and antioxidant activity of polysaccharides from elderberry fruit

Extraction, isolation, structural characterization, and antioxidant activity of polysaccharides from elderberry fruit

Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3

Testosterone Deficiency in Sickle Cell Disease: Recognition and Remediation

Contact Info

Product

Resources

About