Razinah Sharif

Cognitive impairment, genomic instability and trace elements

Cognitive impairments are often related to aging and micronutrient deficiencies. Various essential micronutrients in the diet are involved in age-altered biological functions such as, zinc, copper, iron, and selenium that play pivotal roles either in maintaining and reinforcing the antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for biological functions. Genomic stability is one of the leading causes of cognitive decline and deficiencies or excess in trace elements are two of the factors relating to it. In this review, we report and discuss the role of micronutrients in cognitive impairment in relation to genomic stability in an aging population. Telomere integrity will also be discussed in relation to aging and cognitive impairment, as well as, the micronutrients related to these events. This review will provide an understanding on how these three aspects can relate with each other and why it is important to keep a homeostasis of micronutrients in relation to healthy aging. Micronutrient deficiencies and aging process can lead to genomic instability.

DNA damage, copper and lead associates with cognitive function among older adults

BackgroundA cross sectional study was conducted in a group of 317 subjects older than 60 in Malaysia, aimed to determine risk factors associated with cognitive impairment in older adults, focusing on trace elements and DNA damage.MethodCognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels.ResultsA total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05).ConclusionHigh levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.

Antioxidant, Anti-inflammatory, and Genomic Stability Enhancement Effects of Zinc l-carnosine: A Potential Cancer Chemopreventive Agent?

ABSTRACT Cancer is one of the major causes of death worldwide, and the incidence and mortality rates of cancer are expected to rise tremendously in the near future. Despite a better understanding of cancer biology and advancement in cancer management, current strategies in cancer treatment remain costly and ineffective. Hence, instead of putting more efforts to search for new cancer cures, attention has now been shifted to the development of cancer chemopreventive agents as a preventive measure for cancer formation. It is well known that neoplastic transformation of cells is multifactorial, and the occurrence of oxidative stress, chronic inflammation, and genomic instability events has been implicated in the carcinogenesis of cells. Zinc l-carnosine (ZnC), which is clinically used as gastric ulcer treatment in Japan, has been suggested to have the potential in preventing cancer development. Multiple studies have revealed that ZnC possesses potent antioxidant, anti-inflammatory, and genomic stability enhancement effects. Thus, this review provides some mechanistic insight into the antioxidant, anti-inflammatory, and genomic stability enhancement effects of ZnC in relevance to its chemopreventive potential.

Modifiable factors associated with bone health in Malaysian adolescents utilising calcaneus quantitative ultrasound

Maximizing bone mineral accrual to attain an optimal peak bone mass (PBM), particularly during adolescence, appears to be an effective protective strategy in the prevention of osteoporosis. This study aimed to evaluate the influence of physical activity (PA), fat mass (FM), lean mass (LM), body mass index (BMI), calcium, or combination of vitamin D supplement intake, smoking and alcohol drinking status on bone health assessed by calcaneus quantitative ultrasound (QUS) in a healthy adolescent population. The participants comprised of 920 male and female secondary school adolescents aged 15–17 years old. Quantitative ultrasound measurements of the left heel were performed using Lunar Achilles EX II, which included results of broadband ultrasound attenuation (BUA), speed of sound (SOS), and a calculated stiffness index (SI). Multivariable linear regression analyses revealed that—PA was positively associated with all three QUS indices in both genders; BMI was positively associated with SI and SOS in females; LM was positively associated with BUA in both genders; and FM was negatively associated with SI in females. These variables accounted for 32.1%, 21.2% and 29.4% of females’ SOS, BUA and SI variances (p<0.001), respectively and 23.6%, 15.4% and 17.2% of males’ SOS, BUA and SI variances (p<0.001), respectively. Promoting health benefits from physical activity could influence bone status and consequently improve PBM, which is a potent protective determinant against osteoporosis in adulthood.

Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 murine macrophages cell line via activation of Nrf2/HO-1 signaling pathway

Abstract Context: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer. Objective: In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. Materials and methods: We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay. Results: Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine. Conclusion: Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.