Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking

© 2015 Elsevier Ltd. An adverse in-utero environment is increasingly recognized to predispose to chronic disease in adulthood. Maternal smoking remains the most common modifiable adverse in-utero exposure leading to low birth weight, which is strongly associated with chronic kidney disease (CKD) in later life. In order to investigate underlying mechanisms for such susceptibility, female Balb/c mice were sham or cigarette smoke-exposed (SE) for 6 weeks before mating, throughout gestation and lactation. Offspring kidneys were examined for oxidative stress, expression of mitochondrial proteins, mitochondrial structure as well as renal functional parameters on postnatal day 1, day 20 (weaning) and week 13 (adult age). From birth throughout adulthood, SE offspring had increased renal levels of mitochondrial-derived reactive oxygen species (ROS), which left a footprint on DNA with increased 8-hydroxydeoxyguanosin (8-OHdG) in kidney tubular cells. Mitochondrial structural abnormalities were seen in SE kidneys at day 1 and week 13 along with a reduction in oxidative phosphorylation (OXPHOS) proteins and activity of mitochondrial antioxidant Manganese superoxide dismutase (MnSOD). Smoke exposure also resulted in increased mitochondrial DNA copy number (day 1-week 13) and lysosome density (day 1 and week 13). The appearance of mitochondrial defects preceded the onset of albuminuria at week 13. Thus, mitochondrial damage caused by maternal smoking may play an important role in development of CKD at adult life

L-carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring

© 2015 the American Physiological Society. Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of L-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I–V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that L-carnitine administration in cigarette smokeexposed mothers mitigates these deleterious renal consequence

Impact of maternal e-cigarette vapor exposure on renal health in the offspring

© 2019 New York Academy of Sciences. Maternal smoking during pregnancy is a significant risk factor of renal pathology in the offspring. E-cigarettes are perceived to be a safe option and are increasingly used by pregnant women either continuously during pregnancy or as a replacement for tobacco cigarettes. This study aimed to determine the effects of replacing tobacco cigarettes with e-cigarettes during pregnancy, and continuous e-cigarette use during pregnancy on the offspring's kidneys. Female Balb/c mice were exposed to either air (sham) or tobacco cigarette smoke (SE) for 6 weeks prior to mating, during gestation and lactation. A subset of the “SE group” received e-cigarette vapor (containing nicotine) after mating until pups weaned. Additional female mice were continuously exposed to e-vapor (either with or without nicotine) for 6 weeks prior to mating until pups weaned. Kidneys and urine from the male offspring were assessed at postnatal day 1, day 20 (weaning), and 13 weeks of age (adulthood). E-cigarette replacement was less detrimental to renal development and albuminuria than continuous SE during pregnancy. However, continuous e-vapor exposure during pregnancy increased markers of oxidative stress, inflammation, and fibrosis in the adult offspring, independent of nicotine. E-cigarette use during pregnancy confers future risk to the offspring's kidneys

L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury

© 2018, The Author(s). There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress

MitoQ supplementation prevent long-term impact of maternal smoking on renal development, oxidative stress and mitochondrial density in male mice offspring

© 2018 The Author(s). To investigate the effect of maternal MitoQ treatment on renal disorders caused by maternal cigarette smoke exposure (SE). We have demonstrated that maternal SE during pregnancy increases the risk of developing chronic kidney disease (CKD) in adult offspring. Mitochondrial oxidative damage contributes to the adverse effects of maternal smoking on renal disorders. MitoQ is a mitochondria-targeted antioxidant that has been shown to protect against oxidative damage-related pathologies in many diseases. Female Balb/c mice (8 weeks) were divided into Sham (exposed to air), SE (exposed to cigarette smoke) and SEMQ (exposed to cigarette smoke with MitoQ supplemented from mating) groups. Kidneys from the mothers were collected when the pups weaned and those from the offspring were collected at 13 weeks. Maternal MitoQ supplementation during gestation and lactation significantly reversed the adverse impact of maternal SE on offspring's body weight, kidney mass and renal pathology. MitoQ administration also significantly reversed the impact of SE on the renal cellular mitochondrial density and renal total reactive oxygen species in both the mothers and their offspring in adulthood. Our results suggested that MitoQ supplementation can mitigate the adverse impact of maternal SE on offspring's renal pathology, renal oxidative stress and mitochondrial density in mice offspring

Publisher Correction: Non-invasive assessment of exfoliated kidney cells extracted from urine using multispectral autofluorescence features (Scientific Reports, (2021), 11, 1, (10655), 10.1038/s41598-021-89758-4)

In the original version of this Article Saabah B. Mahbub and Long T. Nguyen were omitted as equally contributing authors. Additionally, Sonia Saad and Ewa M. Goldys were omitted as jointly supervised authors. This error has now been corrected in the PDF version of the Article; the HTML version was correct from the time of publication

Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage.

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM2.5 (PM2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM2.5 exerted transgenerational impairment on lung health

Main factors of Kota Kinabalu residents tend to use public transport

Transportation and movement of goods are one of the essential human needs, and special attention is placed on the planning of a large city. It has always played an essential role in the development of society, initially concerning trade routes and harbor, but more recently about land and air-based systems. Therefore, in a particular area where the population growth keeps increasing as in Kota Kinabalu, there is a need to implement a good transportation system to ensure proper traffic flow. This paper surveys the reaction of 450 respondents towards the existing public transportation provided in Kota Kinabalu city through a questionnaire distributed via online form. The main aim of this research is to find out the main factor of Kota Kinabalu residents tends to use public transport. Based on the Chi-square analysis, the age and gender of Kota Kinabalu residents have a significant influence on the frequency of public transport usage in Kota Kinabalu. The results of the study also showed that the main factor of Kota Kinabalu tend to use public transports are the reliability of public transport and its drop-off consistency. Meanwhile, the most factors which need to be enhanced are the cleanliness and comfort of the existing public transport in Kota Kinabalu, Sabah

Pilot study for the modelling of congestion pricing in Kota Kinabalu, Sabah

Congestion pricing is a policy at which road users being charged with certain amount for using particular road during peak hours. It is as much about meeting the demand of car drivers for road space as allocating road space between road users. It has been successfully implemented in some other countries such as Stockholm, London and Singapore with various scheme of congestion pricing. Hence, the main aim of this pilot study is to evaluate and create model based on the willingness of the Kota Kinabalu City residents’ to shift to public transport due to the implementation of congestion pricing. A total of 60 respondents were randomly chosen within Kota Kinabalu City. Data collection is being conducted using stated preference survey and analysed with Microsoft Office Excel 2010 in order to conduct regression analysis and develop a logistic transport model analysis. It is found that the number of people who willing to shift to public transport is parallel with the congestion charge amount. The results from this pilot study indicate that 71.67% of respondents are willing to shift to public transport when the congestion charge price is RM4.00. This study can give contribution for further transportations planning in order to achieve sustainable transportations in Kota Kinabalu, Sabah

Main factors of Kota Kinabalu residents tend to use the private vehicle

Kota Kinabalu is the capital city of Sabah which acts as economic and administration centre and fondly known as KK. The migration of people due to wide opportunities has enhanced the population growth drastically. Unexpectedly, this led to the increase of the travel demand. This has been proven as the number of vehicles travelling in and out of the city grows by 8.3% annually by the number of roads grows at a slower rate, causing worst traffic congestion mainly during peak hours. Hence, this study has been conducted in order to determine the relationship between variables and car ownership in Kota Kinabalu, the relationship between variables with the type of vehicles use for travelling in Kota Kinabalu City as well as to study the factor of Kota Kinabalu residents tend to use the private vehicles in Kota Kinabalu City. An online survey being conducted via Google Form to obtain the findings and chi-square test has been done to analyse the data. It is found that the most factors that encourage people to use private vehicles in Kota Kinabalu City are security concerns, hygiene as well as the time and destinations flexibility