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Protective Role of Natural Products in Cisplatin-Induced Nephrotoxicity

Ridzuan NRA, Rashid NA, Othman F, Budin SB, Hussan F, Teoh SL

Mini Rev Med Chem, 2019;19(14):1134-1143.
PMID: 30894108 DOI: 10.2174/1389557519666190320124438

Cisplatin is a widely used antineoplastic agent for the treatment of metastatic tumors, advanced bladder cancer and many other solid tumors. However, at higher doses, toxicities such as nephrotoxicity may appear. Cisplatin leads to DNA damage and subsequently renal cell death. Besides that, oxidative stress is also implicated as one of the main causes of nephrotoxicity. Several studies showed that numerous natural products: ginseng, curcumin, licorice, honey and pomegranate were able to reduce the oxidative stress by restoring the levels of antioxidant enzymes and also at the same time act as an anti-inflammatory agent. Furthermore, pre-treatment with vitamin supplementation, such as vitamin C, E and riboflavin markedly decreased serum urea and increased the levels of antioxidant enzymes in the kidney even after cisplatin induction in cancer patients. These natural products possess potent antioxidant and anti-inflammatory medicinal properties, and they can be safely used as a supplementary regime or combination therapy against cisplatin-induced nephrotoxicity. The present review focused on the protective role of a few natural products which is widely used in folk medicines in cisplatin-induced nephrotoxicity.

Matched MeSH terms: Riboflavin
Riboflavin content of foods

Leong PC

Journal of the Malaya Branch of the British Medical Association, 1941;5:104-8.

Matched MeSH terms: Riboflavin
Fulltext Somatic Embryogenesis and Plantlet Regeneration in the Carica papaya L. cv. Eksotika

Al-Shara B, Taha RM, Mohamad J, Elias H, Khan A

Plants (Basel), 2020 Mar 12;9(3).
PMID: 32178429 DOI: 10.3390/plants9030360

A highly efficient protocol for regeneration of Carica papaya L. cv. Eksotika somatic embryos from immature zygotic embryos was developed. This study was designed to overcome the obstacles in regeneration of somatic embryos from immature zygotic embryos of "Eksotika", especially problems associated with formation of better root quality and callus formation at the base of somatic embryos. Somatic embryos were generated by incubation of immature zygotic embryos in half-strength salt Murashige and Skoog (MS) medium with full-strength vitamins supplemented with 7.5 mg L-1 2,4-D, 100 mg L-1 L-glutamine, 50 mg L-1myo-inositol, 45 mg L-1 adenine sulphate, 0.33% gelrite, and 6% sucrose, followed by transfer to maturation medium consisting of ½ MS medium supplemented with 5 mg L-1 phloroglucinol, 100 mg L-1 L-glutamine, 100 mg L-1myo-inositol, 68 mg L-1 adenine sulphate, 0.38% gelrite, and 3% sucrose. After that, well-formed somatic embryos were transferred to MS medium containing 3% sucrose and 0.8% agar for shoot production. The embryos were elongated in MS medium supplemented with 1 mg L-1 gibberellic acid, 0.5 mg L-1 indole-3-butyric acid, 100 mg L-1myo-inositol, and 3.76 mg L-1 riboflavin. Root regeneration was achieved on MS medium containing 7.9 mg L-1 phloroglucinol and supported with vermiculite after 4 days of cultivation on ½ MS medium with 2 mg L-1 indole-3-butyric acid. After the rooting phase, in vitro plantlets were acclimatized in peat moss soil.

Matched MeSH terms: Riboflavin
Some observations on food deficiency diseases in Malaya

Pallister RA

Journal of the Malaya Branch of the British Medical Association, 1940;4:191-97.

Matched MeSH terms: Riboflavin Deficiency
Stimulation of erythrocyte glutathione reductase activity by flavin adenine dinucleotide (FAD) in Malaysian adults and newborns and their parents

Luan Eng LI, Ng T, Wan WP, Ganesan J

Br J Haematol, 1975 Nov;31(3):337-42.
PMID: 1201246

A study of glutathione reductase (GR) activity and its stimulation by flavin adenine dinucleotide (FAD) in erythrocytes of Malaysian newborns and adults of different racial groups showed that GR stimulation by FAD was greater than 20% in 50% of 866 newborns (57% of Malays, 55% of Indians and 41% of Chinese) and 54% of 274 adults (46% of Malays, 65% of Indians and 45% of Chinese). There was a significant negative correlation between GR activity and percentage FAD stimulation in both newborns and adults in all racial groups. Low GR activity and a high percentage FAD stimulation were more prevalent among parents of newborns with low GR activity than among parents of newborns with higher GR activity. Administration of riboflavin to mothers with low GR activity resulted in increased GR activity and a decreased percentage of FAD stimulation. None of the individuals examined had clear clinical manifestations of riboflavin deficiency. It is concluded that subclinical riboflavin deficiency leading to low GR activity is prevalent in Malaysia among adults and newborns, especially among Malays and Indians.

Matched MeSH terms: Riboflavin/therapeutic use
Suboptimal Biochemical Riboflavin Status Is Associated with Lower Hemoglobin and Higher Rates of Anemia in a Sample of Canadian and Malaysian Women of Reproductive Age

Aljaadi AM, How RE, Loh SP, Hunt SE, Karakochuk CD, Barr SI, et al.

J Nutr, 2019 Nov 01;149(11):1952-1959.
PMID: 31318024 DOI: 10.1093/jn/nxz151

BACKGROUND: Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood.
OBJECTIVES: We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia.
METHODS: Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n = 206) and Malaysia (n = 210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia.
RESULTS: EGRac (mean ± SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49 ± 0.17 compared with 1.38 ± 0.11). Likewise, riboflavin biomarker deficiency (EGRac ≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n = 416), EGRac values were negatively associated with hemoglobin concentration (r = -0.18; P riboflavin deficiency (EGRac ≥1.40) were twice as likely to present with anemia (adjusted OR: 2.38; 95% CI: 1.08, 5.27) compared with women with EGRac <1.40.
CONCLUSIONS: Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation.

Matched MeSH terms: Riboflavin/blood*; Riboflavin Deficiency/blood*; Riboflavin Deficiency/complications*; Riboflavin Deficiency/epidemiology
Synergistic effects of VE-TPGS and riboflavin in crosslinking of dentine

Daood U, Matinlinna JP, Fawzy AS

Dent Mater, 2019 02;35(2):356-367.
PMID: 30528297 DOI: 10.1016/j.dental.2018.11.031

OBJECTIVE: Effect of d-alpha-tocopheryl poly(ethyleneglycol)-1000-succinate (VE-TPGS) with riboflavin-5'-phosphate solution on crosslinking of dentine collagen was investigated to analyze collagen's structural integrity.
METHODS: VE-TPGS was added to RF-solution, at RF/VE-TPGS (w/w) ratios of 0.125/0.250 and 0.125/0.500. Demineralized dentine beams were used (10wt.% phosphoric acid), rinsed using deionized-water and analysed using ELISA (Human MMP2 ELISA; Human CTSK/Cathepsin-K for MMP2 and Cathepsin K analysis). AFM of dentine collagen-fibrils structure was done before and after dentine specimens' placement in mineralization solution and tested after 14days in artificial saliva/collagenase (AS/Co) solution. The specimens were tested after 24h in mineralization solution for surface/bulk elastic modulus. Nano-indentation was carried out for each specimen on intertubular-dentine with lateral spacing of 400nm. Reduced elastic-modulus and nano-hardness were calculated and collagen content was determined using hydroxyproline-assay. Micro-Raman were performed. TEM was carried out to study structural variations of dentine-collagen in artificial-saliva (collagenase). Data were presented as mean±standard deviation and analyzed by SPSS v.15, by analysis of variance.
RESULTS: Synergetic effect of VE-TPGS was observed with RF through higher structural integrity of dentine collagen-fibrils shown by TEM/AFM. Superior surface/bulk mechanical stability was shown by nano-indentation/mechanical testing. Improvement in collagenase degradation resistance for hydroxyproline release was observed and lower endogenous-protease release of MMP-2/Cathepsin-K. Raman-analysis analysed chemical interactions between RF and collagen confirming structural-integrity of collagen fibrils after crosslinking. After 24h mineralization, AFM showed mineral depositions in close association with dentine-collagen fibrils with RF/VE-TPGS formulations.
SIGNIFICANCE: Potential synergetic effect of RF/VE-TPGS was observed by reflection of higher structural integrity and conformational-stability of dentine-collagen fibrils.

Matched MeSH terms: Riboflavin*
Which aging group prone to have inadequate nutrient intake?: TUA study

Nik Nur Izzati Nik Mohd Fakhruddin, Suzana Shahar, Nurul Atiqah Abd Aziz, Roslee Rajikan, Hanis Mastura Yahya

Sains Malaysiana, 2016;45:1381-1391.

Older adults quite often had an inadequate diet leading to micronutrient deficiencies and impaired immune response with subsequent development of degenerative diseases. This study aimed to determine the adequacy of energy and nutrient intake and its distribution among three aging groups i.e. successful aging (SA), usual aging (UA) and mild cognitive impairment (MCI). This is a cross-sectional study involving a large sample size (n = 2322) of older adults recruited through multistage random sampling from four states of Malaysia. An interview was conducted to measure dietary intake, neurocognitive status and functional status by using the Diet History Questionnaire (DHQ), Mini-Mental State Examination (MMSE), Rey Auditory Learning Test (RAVLT), Geriatric Depression Scale (GDS), Instrumental Activity of Daily Living (IADL) and Quality of Life Questionnaire. For comparison of dietary intake, a sub-sample of 173 respondents from each aging groups were matched and selected using a comparative cross-sectional approach. Women in SA group had the highest mean intake of vitamin A, calcium (p <0.05), vitamin C, riboflavin and iron (p<0.001). The same aging group also achieved the highest RNI percentage for the same nutrients. More than 80% of respondents for all aging groups did not met the recommended nutrient intake (RNI) for vitamin E, thiamin, niacin, folate, calcium and zinc. In women, MCI respondents were more likely to have an inadequate intake of vitamin A, C, riboflavin and iron followed by UA and SA. Inadequate vitamin E, niacin, folate and calcium were prevalent among all gender and aging groups. There is a need to further distinguish specific dietary patterns associated with these three aging groups to promote optimal nutrient intake for cognitive health.

Matched MeSH terms: Riboflavin