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GR15 peptide of S-adenosylmethionine synthase (SAMe) from Arthrospira platensis demonstrated antioxidant mechanism against H2O2 induced oxidative stress in in-vitro MDCK cells and in-vivo zebrafish larvae model

Velayutham M, Guru A, Arasu MV, Al-Dhabi NA, Choi KC, Elumalai P, et al.

J Biotechnol, 2021 Dec 10;342:79-91.
PMID: 34751134 DOI: 10.1016/j.jbiotec.2021.10.010

GR15 is a short molecule or peptide composed of aliphatic amino acids and possesses to have antioxidant properties. The GR15, 1GGGAFSGKDPTKVDR15 was identified from the protein S-adenosylmethionine synthase (SAMe) expressed during the sulfur departed state of Arthrospira platensis (spirulina or cyanobacteria). The in-silico assessment and the structural features of GR15 showed its antioxidant potency. Real-time PCR analysis found the up-regulation of ApSAMe expression on day 15 against oxidative stress due to 10 mM H2O2 treatment in A. platensis (Ap). The antioxidant activity of GR15 was accessed by the cell-free antioxidant assays such as ABTS, SARS, HRAS and NO; the results showed dose-dependent antioxidant activity. The toxicity assay was performed in both in vitro and in vivo models, in which peptide does not exhibit any toxicity in MDCK cell and zebrafish embryos. The intercellular ROS reduction potential of GR15 peptide was also investigated in both in vitro and in vivo models including LDH assay, antioxidant enzymes (SOD and CAT), and fluorescent staining assay (DCFDA, Hochest and Acridine orange sting) was performed; the results showed that the GR15 peptide was effectively reduced the ROS level. Further, RT-PCR demonstrated that GR15 enhanced the antioxidant property and also up-regulated the antioxidant gene, thus reduced the ROS level in both in vitro and in vivo models. Based on the results obtained from this study, we propose that GR15 has the potential antioxidant ability; hence further research can be directed towards the therapeutic product or drug development against disease caused by oxidative stress.

Matched MeSH terms: Oxidative Stress
Fulltext The role of lycopene for the amelioration of glycaemic status and peripheral antioxidant capacity among the Type II diabetes mellitus patients: a case-control study

Leh HE, Mohd Sopian M, Abu Bakar MH, Lee LK

Ann Med, 2021 12;53(1):1059-1065.
PMID: 34180336 DOI: 10.1080/07853890.2021.1943515

BACKGROUND: The use of lycopene as a complementary medicine for Type II diabetes mellitus (T2DM) is limited and controversial. This study evaluated the effect of lycopene intake on the changes of glycaemic status and antioxidant capacity among the T2DM patients.
PATIENTS AND METHODS: This case-control study involved the participation of 87 patients and 122 healthy individuals. Lycopene intake was assessed by using a food frequency questionnaire. The peripheral antioxidant capacity among the T2DM patients was evaluated. Glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were measured as indications of glycaemic status.
RESULTS: Peripheral antioxidant capacity was significantly lower in the T2DM group. Direct positive correlations were found between the lycopene intake and peripheral antioxidant level among the T2DM patients. Contrarily, HbA1c and FPG levels decreased significantly with the higher lycopene intake.
CONCLUSIONS: T2DM patients with a higher lycopene intake showed a greater peripheral antioxidant capacity and better glycaemic control. Lycopene may act to ameliorate oxidative stress and improve the pathophysiology of T2DM.

Matched MeSH terms: Oxidative Stress/drug effects*
Fulltext Phytochemical analysis and protective effects of Vaccinium macrocarpon (cranberry) in rats (Rattus norvegicus) following ethylene oxide-induced oxidative insult

Rasool M, Malik A, Abdul Basit Ashraf M, Mubbin R, Ayyaz U, Waquar S, et al.

Bioengineered, 2021 12;12(1):4593-4604.
PMID: 34346287 DOI: 10.1080/21655979.2021.1955528

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.

Matched MeSH terms: Oxidative Stress/drug effects*
Fulltext The role of natural antioxidants in cisplatin-induced hepatotoxicity

Abd Rashid N, Abd Halim SAS, Teoh SL, Budin SB, Hussan F, Adib Ridzuan NR, et al.

Biomed Pharmacother, 2021 Dec;144:112328.
PMID: 34653753 DOI: 10.1016/j.biopha.2021.112328

Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.

Matched MeSH terms: Oxidative Stress/drug effects*
Fulltext Clinacanthus nutans attenuates atherosclerosis progression in rats with type 2 diabetes by reducing vascular oxidative stress and inflammation

Azemi AK, Mokhtar SS, Sharif SET, Rasool AHG

Pharm Biol, 2021 Dec;59(1):1432-1440.
PMID: 34693870 DOI: 10.1080/13880209.2021.1990357

CONTEXT: Atherosclerosis predisposes individuals to adverse cardiovascular events. Clinacanthus nutans L. (Acanthaceae) is a traditional remedy used for diabetes and inflammatory conditions.
OBJECTIVES: To investigate the anti-atherosclerotic activity of a C. nutans leaf methanol extract (CNME) in a type 2 diabetic (T2D) rat model induced by a high-fat diet (HFD) and low-dose streptozotocin.
MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into five groups: non-diabetic fed a standard diet (C), C + CNME (500 mg/kg, orally), diabetic fed an HFD (DM), DM + CNME (500 mg/kg), and DM + Metformin (DM + Met; 300 mg/kg). Treatment with oral CNME and metformin was administered for 4 weeks. Fasting blood glucose (FBG), serum lipid profile, atherogenic index (AI), aortic tissue superoxide dismutase levels (SOD), malondialdehyde (MDA), and tumour necrosis factor-alpha (TNF-α) were measured. The rats' aortas were stained for histological analysis and intima-media thickness (IMT), a marker of subclinical atherosclerosis.
RESULTS: The CNME-treated diabetic rats had reduced serum total cholesterol (43.74%; p = 0.0031), triglycerides (80.91%; p = 0.0003), low-density lipoprotein cholesterol (56.64%; p = 0.0008), AI (51.32%; p stress, inflammation, and serum AI. Continued studies on atherosclerotic animal models are suggested.

Matched MeSH terms: Oxidative Stress/drug effects
Fulltext Role of neurotoxicants in the pathogenesis of Alzheimer's disease: a mechanistic insight

Nisa FY, Rahman MA, Hossen MA, Khan MF, Khan MAN, Majid M, et al.

Ann Med, 2021 Dec;53(1):1476-1501.
PMID: 34433343 DOI: 10.1080/07853890.2021.1966088

Alzheimer's disease (AD) is the most conspicuous chronic neurodegenerative syndrome, which has become a significant challenge for the global healthcare system. Multiple studies have corroborated a clear association of neurotoxicants with AD pathogenicity, such as Amyloid beta (Aβ) proteins and neurofibrillary tangles (NFTs), signalling pathway modifications, cellular stress, cognitive dysfunctions, neuronal apoptosis, neuroinflammation, epigenetic modification, and so on. This review, therefore, aimed to address several essential mechanisms and signalling cascades, including Wnt (wingless and int.) signalling pathway, autophagy, mammalian target of rapamycin (mTOR), protein kinase C (PKC) signalling cascades, cellular redox status, energy metabolism, glutamatergic neurotransmissions, immune cell stimulations (e.g. microglia, astrocytes) as well as an amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2) and other AD-related gene expressions that have been pretentious and modulated by the various neurotoxicants. This review concluded that neurotoxicants play a momentous role in developing AD through modulating various signalling cascades. Nevertheless, comprehension of this risk agent-induced neurotoxicity is far too little. More in-depth epidemiological and systematic investigations are needed to understand the potential mechanisms better to address these neurotoxicants and improve approaches to their risk exposure that aid in AD pathogenesis.Key messagesInevitable cascade mechanisms of how Alzheimer's Disease-related (AD-related) gene expressions are modulated by neurotoxicants have been discussed.Involvement of the neurotoxicants-induced pathways caused an extended risk of AD is explicited.Integration of cell culture, animals and population-based analysis on the clinical severity of AD is addressed.

Matched MeSH terms: Oxidative Stress
Life cycle assessment of environmental impacts associated with oxidative desulfurization of diesel fuels catalyzed by metal-free reduced graphene oxide

Lin S, Ng SF, Ong WJ

Environ Pollut, 2021 Nov 01;288:117677.
PMID: 34273765 DOI: 10.1016/j.envpol.2021.117677

This study aimed to analyze the environmental impacts of the oxidative desulfurization (ODS) process catalyzed by metal-free reduced graphene oxide (rGO) through life cycle assessment (LCA). The environmental impacts study containing the rGO production process, the ODS process, the comparison of different oxidants and solvents was developed. This study was performed by using ReCiPe 2016 V1.03 Hierarchist midpoint as well as endpoint approach and SimaPro software. For the production of 1 kg rGO, the results showed that hydrochloric acid (washing), sulfuric acid (mixing), hydrazine (reduction) and electricity were four main contributors in this process, and this process showed a significant impact on human health 14.21 Pt followed by ecosystem 0.845 Pt and resources 0.164 Pt. For the production of 1 kg desulfurized oil (400 ppm), main environmental impacts were terrestrial ecotoxicity (43.256 kg 1,4-DCB), global warming (41.058 kg CO2), human non-carcinogenic toxicity (19.570 kg 1,4-DCB) and fossil resource scarcity (13.178 kg oil), and the main contributors were electricity, diesel oil and acetonitrile. The whole ODS process also showed a greatest effect on human health. For two common oxidants hydrogen peroxide and oxygen used in ODS, hydrogen peroxide showed a greater impact than oxygen. On the other hand, for three common solvents employed in ODS, N-methyl-2-pyrrolidone had a more serious impact on human health followed by acetonitrile and N,N-dimethylformamide. As such, LCA results demonstrated the detailed environmental impacts originated from the catalytic ODS, hence elucidating systematic guidance for its future development toward practicality.

Matched MeSH terms: Oxidative Stress
Fulltext Therapeutic Approach of Flavonoid in Ameliorating Diabetic Cardiomyopathy by Targeting Mitochondrial-Induced Oxidative Stress

Sapian S, Taib IS, Latip J, Katas H, Chin KY, Mohd Nor NA, et al.

Int J Mol Sci, 2021 Oct 27;22(21).
PMID: 34769045 DOI: 10.3390/ijms222111616

Diabetes cardiomyopathy is one of the key factors of mortality among diabetic patients around the globe. One of the prior contributors to the progression of diabetic cardiomyopathy is cardiac mitochondrial dysfunction. The cardiac mitochondrial dysfunction can induce oxidative stress in cardiomyocytes and was found to be the cause of majority of the heart morphological and dynamical changes in diabetic cardiomyopathy. To slow down the occurrence of diabetic cardiomyopathy, it is crucial to discover therapeutic agents that target mitochondrial-induced oxidative stress. Flavonoid is a plentiful phytochemical in plants that shows a wide range of biological actions against human diseases. Flavonoids have been extensively documented for their ability to protect the heart from diabetic cardiomyopathy. Flavonoids' ability to alleviate diabetic cardiomyopathy is primarily attributed to their antioxidant properties. In this review, we present the mechanisms involved in flavonoid therapies in ameliorating mitochondrial-induced oxidative stress in diabetic cardiomyopathy.

Matched MeSH terms: Oxidative Stress/drug effects*
Fulltext Antimicrobial activity and mode of action of 1,8-cineol against carbapenemase-producing Klebsiella pneumoniae

Moo CL, Osman MA, Yang SK, Yap WS, Ismail S, Lim SH, et al.

Sci Rep, 2021 10 21;11(1):20824.
PMID: 34675255 DOI: 10.1038/s41598-021-00249-y

Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death.

Matched MeSH terms: Oxidative Stress/drug effects
Model for type 2 diabetes exhibits changes in vascular function and structure due to vascular oxidative stress and inflammation

Azemi AK, Mokhtar SS, Hou LJ, Sharif SET, Rasool AHG

Biotech Histochem, 2021 Oct;96(7):498-506.
PMID: 32957845 DOI: 10.1080/10520295.2020.1823480

We used a type 2 diabetes rat model produced by a high fat diet (HFD) followed by low dose streptozotocin (STZ) to study diabetic vasculopathy. Animals were evaluated for early vascular structural changes, endothelial function, inflammation, lipid profile and oxidative stress. We used 20 male Sprague-Dawley rats divided equally into control and diabetic groups. Diabetic rats were fed an HFD for 4 weeks, injected intraperitoneally with STZ, then sacrificed at week 15. Aortic endothelial nitric oxide synthase (eNOS), aortic superoxide dismutase (SOD), endothelial-dependent and independent relaxation and contraction, intima-media thickness (IMT), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were measured. Histopathological characteristics also were assessed. Diabetic rats exhibited higher fasting blood glucose (FBG), low density lipoprotein, total cholesterol and triglycerides compared to the control group. Aortic endothelium-dependent relaxation due to acetylcholine (ACh) was lower, while aortic endothelium-dependent contraction due to calcium ionophore and endothelium-independent contraction due to phenylephrine (PE) were higher for the diabetic group. eNOS expression was lower in the diabetic group compared to controls. IMT and MDA levels were increased, while SOD activity was decreased in the diabetic group compared to controls. TNF-α was higher in the diabetic group than for controls. Our type 2 diabetes model exhibited endothelial dysfunction associated with early vascular structural changes, dyslipidemia, increased vascular oxidative stress, and inflammation. Therefore, the model is suitable for studying diabetic atherosclerosis.

Matched MeSH terms: Oxidative Stress
Marantodes pumilum Var Alata (Kacip Fatimah) ameliorates derangement in RANK/RANKL/OPG pathway and reduces inflammation and oxidative stress in the bone of estrogen-deficient female rats with type-2 diabetes

Karim K, Giribabu N, Salleh N

Phytomedicine, 2021 Oct;91:153677.
PMID: 34333329 DOI: 10.1016/j.phymed.2021.153677

BACKGROUND: M. pumilum has been claimed to protect the bone against the adverse effect of estrogen deficiency. Additionally, it also exhibits anti-diabetic activity. In view of these, this study aims to identify the mechanisms underlying the bone protective effect of M. pumilum in the presence of both estrogen deficiency and diabetes mellitus (DM).
METHODS: Ovariectomized, diabetic female rats were given M. pumilum leave aqueous extract (MPLA) (50 and 100 mg/kg/day), estrogen, glibenclamide and estrogen plus glibenclamide for 28 consecutive days. At the end of the treatment, fasting blood glucose (FBG), serum insulin, Ca2+, PO43- and bone alkaline phosphatase (BALP) levels were measured. Rats were sacrificed and femur bones were harvested for determination of expression level and distribution of RANK, RANKL, OPG and oxidative stress and inflammatory proteins by molecular biological techniques.
RESULTS: 100 mg/kg/day MPLA treatment decreased the FBG and BALP levels but increased the serum insulin, Ca2+ and PO43- levels in estrogen deficient, diabetic rats. Expression and distribution of RANKL, NF-κB p65, IKKβ, IL-6, IL-1β and Keap-1 decreased however expression and distribution of RANK, OPG, BMP-2, Type-1 collagen, Runx2, TRAF6, Nrf2, NQO-1, HO-1, SOD and CAT increased in the bone of estrogen deficient, diabetic rats which received 100 mg/kg/day MPLA with greater effects than estrogen-only, glibenclamide-only and estrogen plus glibenclamide treatments.
CONCLUSION: MPLA helps to overcome the adverse effect of estrogen deficiency and DM on the bone and thus this herb could potentially be used for the treatment and prevention of osteoporosis in postmenopausal women with diabetes.

Matched MeSH terms: Oxidative Stress
Oxidative torrefaction performance of microalga Nannochloropsis Oceanica towards an upgraded microalgal solid biofuel

Zhang C, Ho SH, Chen WH, Wang R, Show PL, Ong HC

J Biotechnol, 2021 Sep 10;338:81-90.
PMID: 34298023 DOI: 10.1016/j.jbiotec.2021.07.009

Microalgae are a promising feedstock for carbon-neutral biofuel production due to their superior cellular composition. Alternatively, oxidative torrefaction has been recognized as a potential thermochemical technique for microalgal solid biofuel upgrading. Herein, by using microalga N. oceanica as a feedstock, several characterizations are adopted for evaluating the potential of oxidative torrefaction towards microalgal solid biofuel production. The oxidatively torrefied microalgae can be upgraded as lignite. After in-depth analysis, significant change in the surface microstructure of oxidatively torrefied microalgae is largely changed (via wrinkle and fragmentation) The hydrophobicity, thermal decomposition, thermal stability, and aromatization of oxidatively torrefied microalgae can be largely enhanced as the oxidative torrefaction severity increase. With the increasing torrefaction temperature, the hydrophobicity of oxidative torrefied microalgae gradually improved. The decomposition of C-2/3/5, and -OCH3, the CO bonds of CH3CO-, and the aromatization occurs via oxidative torrefaction according to the NMR analysis. For XPS analysis, torrefaction operation significantly decreases the carbide carbon and enhances the graphitization. As a result, the thermal stability of oxidatively torrefied microalgae is improved. Conclusively, the information obtained in this study can provide insights into the evaluation of oxidative torrefaction performance and fuel properties of microalgal solid biofuel, which may help accelerate the advancement of oxidative torrefaction industrialization.

Matched MeSH terms: Oxidative Stress
Fulltext Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells

Maniam S, Maniam S

Int J Mol Sci, 2021 Sep 08;22(18).
PMID: 34575883 DOI: 10.3390/ijms22189722

Targeted chemotherapy has become the forefront for cancer treatment in recent years. The selective and specific features allow more effective treatment with reduced side effects. Most targeted therapies, which include small molecules, act on specific molecular targets that are altered in tumour cells, mainly in cancers such as breast, lung, colorectal, lymphoma and leukaemia. With the recent exponential progress in drug development, programmed cell death, which includes apoptosis and autophagy, has become a promising therapeutic target. The research in identifying effective small molecules that target compensatory mechanisms in tumour cells alleviates the emergence of drug resistance. Due to the heterogenous nature of breast cancer, various attempts were made to overcome chemoresistance. Amongst breast cancers, triple negative breast cancer (TNBC) is of particular interest due to its heterogeneous nature in response to chemotherapy. TNBC represents approximately 15% of all breast tumours, however, and still has a poor prognosis. Unlike other breast tumours, signature targets lack for TNBCs, causing high morbidity and mortality. This review highlights several small molecules with promising preclinical data that target autophagy and apoptosis to induce cell death in TNBC cells.

Matched MeSH terms: Oxidative Stress/drug effects
Fulltext Polystyrene Microplastics Exposure: An Insight into Multiple Organ Histological Alterations, Oxidative Stress and Neurotoxicity in Javanese Medaka Fish (Oryzias javanicus Bleeker, 1854)

Usman S, Abdull Razis AF, Shaari K, Amal MNA, Saad MZ, Mat Isa N, et al.

Int J Environ Res Public Health, 2021 09 07;18(18).
PMID: 34574375 DOI: 10.3390/ijerph18189449

Microplastics (MPs) have become pollutants of concern due to their unknown human health effect and negative impact on terrestrial and aquatic ecosystems. There is increasing number of experimental research on MPs globally with its effects not fully understood; recent animal studies explore its effects on the intestines, yet on other vital organs. Javanese medaka fish was exposed to polystyrene microplastics (PS-MPs) beads for a period of 21 days. Histological alterations, intestinal oxidative stress, permeability and neurotoxicity were evaluated. Significant inflammatory changes and tissue damage were observed in the intestine, liver and kidney. Intestinal oxidative stress and permeability were found to be significantly increased. In the brain, neurotoxicity characterised by a significant induction of oxidative stress, lipid peroxidation and the inhibition of acetylcholinesterase enzyme were elucidated. This study provided an insight into the multiple organ effect of microplastics exposure, necessitating further exploration and identification of biomarkers to be utilised for biomonitoring population at risk in the future.

Matched MeSH terms: Oxidative Stress
Fulltext Potential Health Benefits of Curcumin on Female Reproductive Disorders: A Review

Kamal DAM, Salamt N, Yusuf ANM, Kashim MIAM, Mokhtar MH

Nutrients, 2021 Sep 07;13(9).
PMID: 34579002 DOI: 10.3390/nu13093126

Curcumin is one of the main polyphenolic compounds in the turmeric rhizome. It possesses antioxidant, anti-inflammatory, anti-cancer, anti-arthritis, anti-asthmatic, anti-microbial, anti-viral and anti-fungal properties. This review aims to provide an overview of the potential health benefits of curcumin to treat female reproductive disorders, including polycystic ovary syndrome (PCOS), ovarian failure and endometriosis. Comprehensive information on curcumin was retrieved from electronic databases, which were MEDLINE via EBSCOhost, Scopus and Google Scholar. The available evidence showed that curcumin reduced the high level of androgen in PCOS. Studies in rodents suggest that curcumin resulted in the disappearance of cysts and the appearance of healthy follicles and corpora lutea. Furthermore, animal studies showed curcumin improved the overall function of the ovary in ovarian diseases and reversed the disturbance in oxidative stress parameters. Meanwhile, in vitro and in vivo studies reported the positive effects of curcumin in alleviating endometriosis through anti-inflammatory, anti-proliferative, anti-angiogenic and pro-apoptotic mechanisms. Thus, curcumin possesses various effects on PCOS, ovarian diseases and endometriosis. Some studies found considerable therapeutic effects, whereas others found no effect. However, none of the investigations found curcumin to be harmful. Curcumin clinical trials in endometriosis and ovarian illness are still scarce; thus, future studies need to be conducted to confirm the safety and efficacy of curcumin before it could be offered as a complementary therapy agent.

Matched MeSH terms: Oxidative Stress/drug effects
Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer

Arunachalam A, Lakshmanan DK, Ravichandran G, Paul S, Manickam S, Kumar PV, et al.

Med Oncol, 2021 Sep 04;38(10):122.
PMID: 34482423 DOI: 10.1007/s12032-021-01573-z

A limited number of overexpressed transcription factors are associated with cancer progression in many types of cancer. BTB and CNC homology 1 (BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar). It forms heterodimers with the small musculoaponeurotic fibrosarcoma (MAF) proteins and stimulates or suppresses the expression of target genes under a very low intracellular heme concentration. It possesses a significant regulatory role in heme homeostasis, oxidative stress, cell cycle, apoptosis, angiogenesis, and cancer metastasis progression. This review discusses the current knowledge about how BACH1 regulates cancer metastasis in various types of cancer and other carcinogenic associated factors such as oxidative stress, cell cycle regulation, apoptosis, and angiogenesis. Overall, from the reported studies and outcomes, it could be realized that BACH1 is a potential pharmacological target for discovering new therapeutic anticancer drugs.

Matched MeSH terms: Oxidative Stress
Allium sativum mitigates oxidative damages induced by Microcystin-LR in heart and liver tissues of mice

Ait Abderrahim L, Taibi K, Boussaid M, Al-Shara B, Ait Abderrahim N, Ait Abderrahim S

Toxicon, 2021 Sep;200:30-37.
PMID: 34217748 DOI: 10.1016/j.toxicon.2021.06.018

Microcystins (MCs) are hepatotoxic cyanotoxins implicated in several incidents of human and animal toxicity. Microcystin-(Lysine, Arginine) or MC-LR is the most toxic and encountered variant of MCs where oxidative stress plays a key role in its toxicity. This study investigated the oxidative damages induced in the liver and heart of Balb/C mice by an intraperitoneal injected acute dose of MC-LR. Thereafter, the potential protective effect of garlic (Allium sativum) extract supplementation against such damages was assessed through the evaluation of oxidative stress and cytotoxicity markers. Lipid peroxidation (LPO), carbonyl content (CC), glutathione content (GSH), alkaline phosphatase activity (ALP), lactate dehydrogenase (LDH) and sorbitol dehydrogenase (SDH) activities were measured. Results showed important oxidative damages in hepatic and cardiac cells of mice injected with the toxin. However, these damages have been significantly reduced in mice supplemented with garlic extract. Thus, this study demonstrated for the first time the effective use of garlic as an antioxidant agent against oxidative damages induced by MC-LR. As well, this study supports the use of garlic as a potential remedy against pathologies related to toxic agents.

Matched MeSH terms: Oxidative Stress
Limonin modulated immune and inflammatory responses to suppress colorectal adenocarcinoma in mice model

Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM

Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
PMID: 34009457 DOI: 10.1007/s00210-021-02101-6

Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p stress, and enhancing the endogenous anti-oxidation defense reactions (GSH) in CRC-induced mice.

Matched MeSH terms: Oxidative Stress/drug effects
Fulltext Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet

Suleiman JB, Abu Bakar AB, Noor MM, Nna VU, Othman ZA, Zakaria Z, et al.

Am J Physiol Endocrinol Metab, 2021 Sep 01;321(3):E351-E366.
PMID: 34229480 DOI: 10.1152/ajpendo.00093.2021

The pituitary-gonadal axis plays an important role in steroidogenesis and spermatogenesis, and by extension, fertility. The aim of this study was to investigate the protective role of bee bread, a natural bee product, against obesity-induced decreases in steroidogenesis and spermatogenesis. Thirty-two adult male Sprague-Dawley rats weighing between 200 and 300 g were divided into four groups (n = 8/group), namely: normal control (NC), high-fat diet (HFD), HFD plus bee bread administered concurrently for 12 wk (HFD + B), HFD plus orlistat administered concurrently for 12 wk (HFD + O) groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was suspended in distilled water and given by oral gavage daily for 12 wk. Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and adiponectin, as well as sperm count, motility, viability, normal morphology, and epididymal antioxidants decreased, whereas levels of leptin, malondialdehyde, and sperm nDNA fragmentation increased significantly in the HFD group relative to the NC group. There were significant decreases in the testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme, 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD in the testes of the HFD group. Furthermore, mount, intromission and ejaculatory latencies increased, and penile cGMP level decreased significantly in the HFD group. Supplementation with bee bread significantly reduced leptin level and increased adiponectin level, enhanced sperm parameters and reduced sperm nDNA fragmentation, upregulated the levels of steroidogenic genes and proteins in HFD-induced obese male rats. Bee bread improved steroidogenesis and spermatogenesis by upregulating steroidogenic genes. Therefore, bee bread may be considered as a potential supplementation to protect against infertility in overweight men or men with obesity.NEW & NOTEWORTHY The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.

Matched MeSH terms: Oxidative Stress/drug effects*
Myristic acid defends against testicular oxidative stress, inflammation, apoptosis: Restoration of spermatogenesis, steroidogenesis in diabetic rats

Khalil ASM, Giribabu N, Yelumalai S, Shahzad H, Kilari EK, Salleh N

Life Sci, 2021 Aug 01;278:119605.
PMID: 33989665 DOI: 10.1016/j.lfs.2021.119605

Diabetes mellitus (DM) may lead to testicular-related infertility while Myristic acid (MA) is beneficial to lower hyperglycaemia. Thus, we hypothesized that MA could protect testes against hyperglycaemia-induced damage in DM. DM was induced in adult male rats by high-fat diet consumption for 12 weeks, accompanied by a single dose streptozotocin injection. Following DM confirmation, the rats were fed orally with 10 and 20 mg/kg body weight MA for 28 consecutive days. After completion of treatment, rats were sacrificed and blood, cauda epididymis and testes were harvested. Serum was separated, epididymal sperm was collected for analysis. Molecular studies of the testes were performed by qPCR, Western blotting and immunostaining. MA was found to protect the testes against oxidative stress via preventing the upregulation of RAGE, Keap1, and the downregulation of Nrf2, NQO1, HO1, SOD, CAT and GPx. MA also prevented increase in testicular inflammation and apoptosis, as indicated by low inflammatory (NF-κB p65, IKKβ, TNF-α, IL-1β and iNOS) and apoptosis (Bax and caspase-9), but high anti-apoptosis (Bcl-2) markers' levels. Besides, MA prevented the downregulation of testicular steroidogenic markers (3βHSD, 17βHSD, StAR, ARA-54 and CYP11A1). Sperm analysis revealed near normal sperm count, motility, viability, lower abnormal sperm morphology in diabetic rats received MA. MA also prevented the loss of germ cells via preventing the decreased in cell proliferative marker (PCNA) while maintaining near normal epithelial height, tubular and Leydig cell diameters in the testes in DM. MA protects the testes against damage in DM, thus maintaining spermatogenesis and steroidogenesis, consequently preserving male fertility in diabetes.

Matched MeSH terms: Oxidative Stress/drug effects

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