Displaying publications 81 - 100 of 292 in total

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  1. Perera J, Tan JH, Jeevathayaparan S, Chakravarthi S, Haleagrahara N
    Cell Biosci, 2011;1(1):12.
    PMID: 21711768 DOI: 10.1186/2045-3701-1-12
    Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage.
    Matched MeSH terms: Glutathione Peroxidase
  2. Patro G, Bhattamisra SK, Mohanty BK, Sahoo HB
    Pharmacognosy Res, 2016;8(1):22-8.
    PMID: 26941532 DOI: 10.4103/0974-8490.171099
    OBJECTIVE: Mimosa pudica Linn. (Mimosaceae) is traditionally used as a folk medicine to treat various ailments including convulsions, alopecia, diarrhea, dysentery, insomnia, tumor, wound healing, snake bite, etc., Here, the study was aimed to evaluate the antioxidant potential of M. pudica leaves extract against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (in vitro) and its modulatory effect on rat brain enzymes.
    MATERIALS AND METHODS: Total phenolic, flavonoid contents, and in vitro antioxidant potential against DPPH radical were evaluated from various extracts of M. pudica leaves. In addition, ethyl acetate extract of Mimosa pudica leaves (EAMP) in doses of 100, 200, and 400 mg/kg/day were administered orally for 7 consecutive days to albino rats and evaluated for the oxidative stress markers as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) from rat brain homogenate.
    RESULTS: The ethyl acetate extract showed the highest total phenolic content and total flavonoid content among other extracts of M. pudica leaves. The percentage inhibition and IC50 value of all the extracts were followed dose-dependency and found significant (P < 0.01) as compared to standard (ascorbic acid). The oxidative stress markers as SOD, CAT, and GSH were increased significantly (P < 0.01) at 200 and 400 mg/kg of EAMP treated animals and decreased significantly the TBARS level at 400 mg/kg of EAMP as compared to control group.
    CONCLUSION: These results revealed that the ethyl acetate extract of M. pudica exhibits both in vitro antioxidant activity against DPPH and in vivo antioxidant activity by modulating brain enzymes in the rat. This could be further correlated with its potential to neuroprotective activity due to the presence of flavonoids and phenolic contents in the extract.
    SUMMARY: Total phenolic, flavonoid contents and in-vitro antioxidant potential were evaluated from various extracts of M. pudica leaves. Again, in-vivo antioxidant evaluation from brain homogenate on oxidative stress markers as TBARS, SOD, CAT and GSH from rat was investigated. Our findings revealed that M. pudica possesses both in-vitro and in-vivo antioxidant activity due to presence of phenolics and flavonoids.
    KEYWORDS: 2; 2-diphenyl-1-picrylhydrazyl; Brain homogenate; Flavonoids; Mimosa pudica; Oxidative stress
    Matched MeSH terms: Glutathione
  3. Othman MS, Khonsue W, Kitana J, Thirakhupt K, Robson M, Borjan M, et al.
    Bull Environ Contam Toxicol, 2012 Aug;89(2):225-8.
    PMID: 22722596 DOI: 10.1007/s00128-012-0708-6
    Glutathione-S-Transferase (GST) and metallothionein are important biomarker endpoints in studying the effect of Cd exposure. The purpose of this research was to study the correlation between hepatic GST and metallothionein with hepatic Cd in wild Fejervarya limnocharis exposed to environmental Cd. Results showed that frogs from contaminated sites had significantly higher hepatic metallothionein (3.58 mg/kg wet weight) and GST activity (0.259 μmol/min/mg total protein) than those from the reference site (2.36 mg/kg wet weight and 0.157 μmol/min/mg total protein respectively). There was a significantly positive correlation between hepatic Cd and GST activity (r = 0.802, p = 0.009) but not between hepatic Cd and metallothionein (r = 0.548, p = 0.139). The results concluded that while frogs from the contaminated site had higher GST and metallothionein, only GST showed significant positive correlation with hepatic Cd levels, indicating that hepatic GST activity may be used as a biomarker endpoint.
    Matched MeSH terms: Glutathione Transferase/metabolism*
  4. Onn LC, Ching CS, Lian TY, Foon LV, Chew Hee N, Moi CS
    Environ Toxicol, 2014 Jun;29(6):655-64.
    PMID: 22778066 DOI: 10.1002/tox.21792
    4-Chloro-1,2-phenylenediamine (4-Cl-o-PD) is a halogenated aromatic diamine that was used as a precursor for manufacturing permanent hair dyes. Despite its well-documented mutagenic and carcinogenic effects in a number of in vitro and in vivo models, its cytotoxicity and mode of action have not received similar attention. Here, we investigated the effect of 4-Cl-o-PD on Mardin-Darby canine kidney cells. It induced apoptosis and the evidence suggests its initiation by reactive oxygen species (ROS). The results of various assays used show a dose-dependent (i) decrease in cell viability, (ii) increase in cells at sub-G1 phase and the G0/G1 phase arrested in cell cycle, (iii) increase in intracellular ROS accompanied by depletion of glutathione, and (iv) that apoptotic cell death probably involves activation of both intrinsic and extrinsic pathways.
    Matched MeSH terms: Glutathione/metabolism
  5. Ong FB, Wan Ngah WZ, Top AG, Khalid BA, Shamaan NA
    Int. J. Biochem., 1994 Mar;26(3):397-402.
    PMID: 7910569
    1. The effects of alpha-tocopherol and gamma-tocotrienol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) activities in cultured hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated. 2. Both the alpha-tocopherol and gamma-tocotrienol treated hepatocytes showed significantly higher (P < 0.05) GST activities than untreated hepatocytes prepared from the carcinogen treated rats in the first 3 days of culture. Treatment with alpha-tocopherol and gamma-tocotrienol generally resulted in a tendency to increase the GST activities above that in the untreated hepatocytes. 3. Treatment with high doses (125-250 microM) of alpha-tocopherol and low doses (12.5-25 microM) of gamma-tocotrienol generally resulted in a significant reduction in gamma-GT activities at 1-3 days. gamma-GT activities are reduced as the dose of alpha-tocopherol and gamma-tocotrienol are increased.
    Matched MeSH terms: Glutathione Transferase/metabolism*
  6. Ong FB, Wan Ngah WZ, Shamaan NA, Md Top AG, Marzuki A, Khalid AK
    PMID: 7903615
    1. The effect of tocotrienol and tocopherol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (GGT) activities in cultured rat hepatocytes were investigated. 2. Tocotrienol and tocopherol significantly decreased GGT activities at 5 days in culture but tocotrienol also significantly decreased GGT activities at 1-2 days. 3. Tocotrienol and tocopherol treatment significantly decreased GST activities at 3 days compared to the control but tocotrienol also decreased GST activities at 1-3 days. 4. Tocotrienol showed a more pronounced effect at a dosage of greater than 50 microM tocotrienol at 1-3 days in culture compared to the control.
    Matched MeSH terms: Glutathione Transferase/metabolism*
  7. Ogar I, Egbung GE, Nna VU, Atangwho IJ, Itam EH
    Life Sci, 2019 Feb 15;219:283-293.
    PMID: 30668955 DOI: 10.1016/j.lfs.2019.01.027
    AIMS: Chronic hyperglycaemia in diabetes mellitus (DM) increases the production of free radicals which results in oxidative stress and related disorders such as cardiovascular diseases, compromised hepatic and renal functions. Hyptis verticillata reportedly demonstrated glucose lowering activity in previous studies. The present study therefore evaluated the effect of H. verticillata on hyperglycaemia-induced dyslipidaemia, hepatorenal distortions, oxidative stress, as well as calculated indices of cardiovascular function.

    METHODS: Wistar rats employed for this study consisted of normoglycaemic and diabetic rats in nine experimental groups. The normoglycaemic and diabetic rats were either treated with metformin (500 mg/kg b.w.), quercetin (10 mg/kg b.w.), or ethanol extract of H. verticillata leaf (250 mg/kg b.w. and 500 mg/kg b.w.) administered orally for 28 days.

    KEY FINDINGS: Results revealed that H. verticillata significantly lowered blood glucose level, attenuated dyslipidaemia, decreased atherogenic coefficient, atherogenic and coronary risk indices, and increased cardioprotective index in diabetic rats. Also, H. verticillata significantly decreased serum urea, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and unconjugated bilirubin levels, relative to untreated diabetic rats. Further, H. verticillata increased serum superoxide dismutase, catalase and glutathione peroxidase activities and glutathione level, and decreased malondialdehyde level in diabetic rats in a manner similar to metformin and quercetin. Histopathological investigation of the liver and kidney revealed restored hepatocytes and amelioration of congested interstitial blood vessel of the Bowman's space of the kidneys upon intervention with H. verticillata.

    SIGNIFICANCE: H. verticillata in addition to its anti-hyperglycaemic activity ameliorates oxidative stress, dyslipidaemia, atherogenicity and hepatorenal lesions in DM.

    Matched MeSH terms: Glutathione; Glutathione Peroxidase
  8. Norsidah KZ, Asmadi AY, Azizi A, Faizah O, Kamisah Y
    J Physiol Biochem, 2013 Sep;69(3):441-9.
    PMID: 23208529 DOI: 10.1007/s13105-012-0226-3
    Oxidative stress contributes to cardiovascular diseases. We aimed to study the effects of palm tocotrienol-rich fraction (TRF) on plasma homocysteine and cardiac oxidative stress in rats fed with a high-methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control. Groups 2-6 were fed 1% methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60 and 150 mg/kg diet) was added into the diet of groups 3, 4, 5 and 6. The rats were then killed. Palm TRF at 150 mg/kg and folate supplementation prevented the increase in plasma total homocysteine (4.14 ± 0.33 and 4.30 ± 0.26 vs 5.49 ± 0.25 mmol/L, p < 0.05) induced by a high-methionine diet. The increased heart thiobarbituric acid reactive substance in rats fed with high-methionine diet was also prevented by the supplementations of palm TRF (60 and 150 mg/kg) and folate. The high-methionine group had a lower glutathione peroxidase activity (49 ± 3 vs 69 ± 4 pmol/mg protein/min) than the control group. This reduction was reversed by palm TRF at 60 and 150 mg/kg diet (p < 0.05), but not by folate. Catalase and superoxide dismutase activities were unaffected by both methionine and vitamin supplementations. In conclusion, palm TRF was comparable to folate in reducing high-methionine diet-induced hyperhomocysteinemia and oxidative stress in the rats' hearts. However, palm TRF was more effective than folate in preserving the heart glutathione peroxidase enzyme activity.
    Matched MeSH terms: Glutathione Peroxidase/metabolism
  9. Nor Arfuzir NN, Agarwal R, Iezhitsa I, Agarwal P, Sidek S, Ismail NM
    Neural Regen Res, 2018 Nov;13(11):2014-2021.
    PMID: 30233077 DOI: 10.4103/1673-5374.239450
    Endothelin-1 (ET-1), a potent vasoconstrictor, is involved in retinal vascular dysregulation and oxidative stress in glaucomatous eyes. Taurine (TAU), a naturally occurring free amino acid, is known for its neuroprotective and antioxidant properties. Hence, we evaluated its neuroprotective properties against ET-1 induced retinal and optic nerve damage. ET-1 was administered intravitreally to Sprague-Dawley rats and TAU was injected as pre-, co- or post-treatment. Animals were euthanized seven days post TAU injection. Retinae and optic nerve were examined for morphology, and were also processed for caspase-3 immunostaining. Retinal redox status was estimated by measuring retinal superoxide dismutase, catalase, glutathione, and malondialdehyde levels using enzyme-linked immuosorbent assay. Histopathological examination showed significantly improved retinal and optic nerve morphology in TAU-treated groups. Morphometric examination showed that TAU pre-treatment provided marked protection against ET-1 induced damage to retina and optic nerve. In accordance with the morphological observations, immunostaining for caspase showed a significantly lesser number of apoptotic retinal cells in the TAU pre-treatment group. The retinal oxidative stress was reduced in all TAU-treated groups, and particularly in the pre-treatment group. The findings suggest that treatment with TAU, particularly pre-treatment, prevents apoptosis of retinal cells induced by ET-1 and hence prevents the changes in the morphology of retina and optic nerve. The protective effect of TAU against ET-1 induced retinal and optic nerve damage is associated with reduced retinal oxidative stress.
    Matched MeSH terms: Glutathione
  10. Ngah WZ, Shamaan NA, Said MH, Azhar MT
    Eur Arch Otorhinolaryngol, 1993;250(5):304-7.
    PMID: 8105826
    Plasma gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in normal and nasopharyngeal carcinoma (NPC) patients. No difference in enzyme activities was observed in the three major races of the Malaysian population, i.e. Malay, Chinese and Indian patients. However, plasma gamma-GT, erythrocyte glutathione S-transferase (GST) and GPx activities were significantly increased in all NPC patients, while GR activity remained unchanged. Patients with elevated plasma gamma-GT activities also had increased GST and GPx activities. Plasma gamma-GT and GPx activities were then found to be affected by treatment. Patients with plasma gamma-GT activity greater than 70 IU/l had very poor prognoses but patients with decreased gamma-GT activities were found to be in remission.
    Matched MeSH terms: Glutathione Peroxidase/blood*; Glutathione Reductase/blood*
  11. Ng ZX, Chua KH, Iqbal T, Kuppusamy UR
    Int J Mol Sci, 2013;14(4):7480-91.
    PMID: 23552832 DOI: 10.3390/ijms14047480
    This study aims to investigate potential diabetic retinopathy (DR) risk factors by evaluating the circulating levels of pentosidine, soluble receptor for advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited. Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement. DNR and DR patients showed significantly higher levels of plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients. Proliferative DR patients had significantly higher levels of plasma pentosidine, sRAGE, AOPP and sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level, long duration of diabetes and low sRAGE/pentosidine ratio were determined as the risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR.
    Matched MeSH terms: Glutathione Peroxidase/blood
  12. Ng ZX, Kuppusamy UR, Iqbal T, Chua KH
    Gene, 2013 Jun 1;521(2):227-33.
    PMID: 23545311 DOI: 10.1016/j.gene.2013.03.062
    Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear.
    Matched MeSH terms: Glutathione Peroxidase/genetics; Glutathione Peroxidase/metabolism
  13. Nayak CD, Nayak DM, Raja A, Rao A
    Neurol India, 2008 3 4;56(1):31-5.
    PMID: 18310834
    CONTEXT: Acute oxidative stress following a traumatic head injury (HI) has been implicated in inducing severe secondary brain damage and influencing the clinical outcome of HI patients.

    AIMS: This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators.

    SETTINGS AND DESIGN: Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls.

    MATERIALS AND METHODS: Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR).

    RESULTS: Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls.

    CONCLUSION: Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.

    Matched MeSH terms: Glutathione/blood; Glutathione Reductase/blood
  14. Nayak CD, Nayak DM, Raja A, Rao A
    Indian J Med Sci, 2007 Jul;61(7):381-9.
    PMID: 17611343
    BACKGROUND: Reactive oxygen species are indicated to play a prime role in the pathophysiology of brain damage following a severe head injury (SHI).

    AIM: The current study was designed to understand the time-relative changes and relationship between erythrocyte antioxidant enzyme activities and Glasgow Coma Scale (GCS) scores of SHI patients in the 21-day posttraumatic study period.

    SETTINGS AND DESIGN: The study included 24 SHI patients and 25 age- and sex-matched normal controls (NC). Activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) were assayed in these patients and controls. The GCS scores of these patients were also recorded for the comparative study.

    MATERIALS AND METHODS: Venous blood samples were collected on day 7 (D7) and D21 from SHI patients and NC for the assay of SOD, GR and GSH-Px activities. These changes were correlated with age and changes in GCS scores of patients.

    STATISTICAL ANALYSIS: A one-way analysis of variance (ANOVA) was used to compare mean values of each parameter between group 1 (NC), group 2 (D7 changes in SHI patients) and group 3 (D21 changes in SHI patients). ANOVA was followed by Bonferroni post hoc tests. The Pearson correlation was applied to correlate between the antioxidant parameters and age and GCS scores of these patients.

    RESULTS: A significant increase in erythrocyte SOD and GSH-Px activities was observed in group 3 as compared to groups 1 and 2. The increase in GSH-Px activity was significant in group 2 as compared to group 1. Although not significant, there was an increase in mean GR activity in groups 2 and 3 as compared to group 1.

    CONCLUSION: These findings indicate that SHI patients have shown significantly enhanced erythrocyte SOD and GSH-Px activities during the 21-day posttraumatic study period.

    Matched MeSH terms: Glutathione Peroxidase
  15. Nayak C, Nayak D, Raja A, Rao A
    Neurol Res, 2008 Jun;30(5):461-4.
    PMID: 18953735
    Epidemiologic works reveal that moderate head injury (MHI) is more frequent and a substantial number of these patients develop complications resulting in neurological disabilities. Reactive oxygen species (ROS) play a major role in post-traumatic neuronal damage following traumatic head injury. Thus, the current study analysed the post-traumatic changes in the erythrocyte markers of oxidative damage and the relationship between these parameters and Glasgow coma scale (GCS) scores of MHI patients during the 7 day study period.
    Matched MeSH terms: Glutathione/metabolism*
  16. Nayak C, Nayak D, Bhat S, Raja A, Rao A
    Clin Chem Lab Med, 2007;45(5):629-33.
    PMID: 17484625
    Experimental data indicate that destructive oxidative events reach their peak within the first 24 h after trauma in head injury (HI) and that brain damage occurring due to this impact can be the cause of death or irreversible permanent disabilities in affected patients.
    Matched MeSH terms: Glutathione/blood
  17. Nallappan D, Chua KH, Ong KC, Chong CW, Teh CSJ, Palanisamy UD, et al.
    Food Funct, 2021 Jul 05;12(13):5876-5891.
    PMID: 34019055 DOI: 10.1039/d1fo00539a
    Obesity is a driving factor in the onset of metabolic disorders. This study aims to investigate the effects of the myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract on high-fat diet (HFD)-induced obesity and its associated complications and its influence on uncoupling protein-1 (UCP-1) and gut microbiota in C57BL/6J mice. Mice were randomly assigned into four groups (n = 6) and given a normal diet (ND) or high-fat diet (HFD) for 10 weeks to induce obesity. The HFD groups (continued with HFD) were administered 50 mg kg-1 MD (treatment), 50 mg kg-1 metformin (positive control) and normal saline (HFD and ND controls) daily for four weeks via oral gavage. The ten-week HFD-feeding resulted in hyperglycemia and elevated urinary oxidative indices. The subsequent MD administration caused significant weight reduction without appetite suppression and amelioration of insulin resistance, steatosis and dyslipidemia. Besides, MD significantly reduced lipid hydroperoxides and protein carbonyls in tissue homogenates and urine and elevated Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and reduced glutathione (GSH) and thus, alleviated oxidative stress. The weight reduction was correlated with downregulation of inflammatory markers and the increased UCP-1 level, suggesting weight loss plausibly through thermogenesis. The Akkermansia genus (reflects improved metabolic status) in the HFD50 group was more abundant than that in the HFD group while the non-enzymatic antioxidant markers were strongly associated with UCP-1. In conclusion, MD ameliorates obesity and its related complications possibly via the upregulation of UCP-1 and increased abundance of Akkermansia genus and is promising as a therapeutic agent in the treatment of obesity and its associated metabolic disorders.
    Matched MeSH terms: Glutathione/metabolism
  18. Naidu KR, Kumar KS, Arulselvan P, Reddy CB, Lasekan O
    Arch Pharm (Weinheim), 2012 Dec;345(12):957-63.
    PMID: 23015406 DOI: 10.1002/ardp.201200192
    A series of α-hydroxyphosphonates were synthesized from the reaction of aldehyde (1) with triethylphosphite (2) in the presence of oxone and evaluated for their antioxidant properties against lipid peroxidation, reduced glutathione, superoxide dismutase, and catalase. The majority of the compounds showed promising antioxidant activity. Diethyl anthracen-9-yl (hydroxy) methylphosphonate (3n) is the most potent and biologically active compound against free radicals.
    Matched MeSH terms: Glutathione/metabolism
  19. Nahar N, Mohamed S, Mustapha NM, Lau S, Ishak NIM, Umran NS
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar;394(3):457-467.
    PMID: 33047165 DOI: 10.1007/s00210-020-01989-w
    Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.
    Matched MeSH terms: Glutathione/blood
  20. Nagapan TS, Lim WN, Basri DF, Ghazali AR
    Exp Anim, 2019 Nov 06;68(4):541-548.
    PMID: 31243189 DOI: 10.1538/expanim.19-0017
    Dietary antioxidant supplements such as L-glutathione have gained considerable attention in dermatology and cosmeceutical fields. L-glutathione possesses antiaging, antimelanogenic, antioxidant, and anticancer properties. This study aimed to investigate the inhibitory effects of L-glutathione on melanogenesis activity and oxidative stress in ultraviolet B (UVB)-irradiated BALB/c mice. Eighteen female BALB/c mice were randomly divided into 3 groups: a control group (n=6), a group without UVB irradiation and L-glutathione administration; a UVB irradiated group (n=6), a group irradiated with a UVB dose of 250 mJ/cm2 for 3 min; and a treatment group (n=6), a group irradiated with UVB and treated with 100 mg/kg of L-glutathione by oral gavage. Treatment was given for 14 days, and UVB irradiation was given on days 9, 11, and 13. Oral L-glutathione significantly (P<0.05) reduced lipid peroxidation and elevated superoxide dismutase activity the and glutathione level. L-glutathione also inhibited melanin content and tyrosinase activity significantly (P<0.05) as compared with the UVB-irradiated group. Histopathological examination also showed that L-glutathione reduced the deposition of melanin pigment in the basal layer of the epidermis as compared with that in UVB-irradiated mice. All in all, the present study demonstrated that L-glutathione has the potential to be developed as a photoprotection agent against UVB-induced oxidative stress and melanogenesis.
    Matched MeSH terms: Glutathione/administration & dosage; Glutathione/pharmacology*
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