Lipid hydroperoxides promote muscle atrophy through lysosomal amplification

Reactive oxygen species (ROS) is a cardinal feature of skeletal muscle atrophy. However, ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength.1,2 Here we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by suppression of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. Strikingly, genetic and pharmacologic suppression of muscle LOOH robustly prevented the reduction of both muscle mass and force-generating capacity. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner, and the suppression of autophagic machinery was sufficient to prevent muscle atrophy and weakness. Indeed, the lysosome is essential for the amplification of LOOH induced by oxidative stress. Our findings provide novel insights for the role of LOOH in muscle atrophy including a therapeutic implication by pharmacologic suppression.

The level of products of lipid peroxidation in the blood of piglets at the action feed additive “Sylimevit”

Intensive pig breeding has been reported in the literature to suggest that early weaning of piglets from sows is an extreme stimulus that reduces the protective and adaptive responses of piglets. That is why the aim of the study was to study the effect of the feed additive “Sylimevit” on the level of lipid peroxidation products of piglets after weaning. Two groups of piglets were formed – control and experimental in the amount of 10 individuals in each group, selected on the principle of analogs – age, breed and body weight. During the weaning period, the piglets were kept under the sow in special machines, had constant access to the mother, and from the age of 5 days – free access to concentrated feed. While feeding of animals was carried out in accordance with the norms for a given age of pigs. Prior to the study, a clinical and physiological examination of the piglets was performed. Their general condition and activity when eating food were taken into account. On the 28th day of life, the piglets were weaned from the sow and regrouped from different nests in order to be further maintained during the period of fattening and rearing with a change in the structure of the diet, which served as technological stress for the animals. From the age of 5 days, piglets of all groups were fed pre-starter feed. Piglets of the experimental group, from 21 to 40 days of age, were additionally fed the feed supplement “Sylimevit” at a dose of 100 mg/kg body weight per day. The technological stress of weaning piglets from sows is accompanied by a gradual probable intensification of lipid peroxidation processes. Feeding Sylimevit feed to piglets after weaning helped to reduce the content of intermediate and final products of lipid peroxidation: lipid hydroperoxides – by 52 % (P < 0.001) and TBA-active products – by 22.5 % (P < 0.01). Thus, feeding the piglets of the experimental group of the feed additive “Sylimevit” helped to suppress the processes of lipid peroxidation in animals. Thus, the results of the use of feed additive “Sylimevit” in weaned piglets showed a pronounced antioxidant effect. The components of the feed additive directly interacted with reactive oxygen species and free radicals, preventing the development of oxidative stress.

Systemic lipid peroxidation and skeletal tissues metabolism in animals with simulated posttraumatic osteoarthrosis

ABSTRACTThe role of individual factors in the progressing of degenerative and dystrophic changes of articular cartilage as the focus of pathologic changes in posttraumatic osteoarthrosis (PTOA) has been studied comprehensively. However, no single concept of pathogenetic mechanisms leading to the formation of permanent changes in the affected joint has been represented yet. Therefore, the investigation of lipid peroxidation and skeletal tissues metabolism in animals with simulated PTOA is a challenging and important issue.In 28 non-linear male rats (12 intact control animals and 16 experimental animals with simulated knee OA) we studied the lipid peroxidation rate by the level of lipid hydroperoxides, antioxidant system activity by the indicants of total antioxidant, and thiol statuses. The destruction processes in skeletal tissues were evaluated by the level of hyaluronan, a cartilaginous tissue marker, and subchondral bone turnover makers (fibroblast growth factor-23, osteoprotegerin, sclerostin, osteocalcin).In rats with simulated PTOA, we observed the activation of lipid peroxidation with the accumulation of lipid hydroperoxides in systemic blood flow along with the insignificant decrease of thiol status indicant while the normal antioxidant activity is maintained. We also revealed the significant increase of biopolymer hyaluronan (p<0.05) in a negative change of turnover regulation marker (the significant increase in fibroblast growth factor-23 (p<0.05) with the emerging trend for osteoprotegerin and sclerostin decrease) and bone formation marker (high osteocalcin) as compared to the intact controls.Our findings confirmed that animals with simulated PTOA featured rearranging of skeletal tissues as compared to intact animals. This process involved degenerative destruction of both chondral and osseous tissues along with profound prooxidant activity and relative incompetence of the thiol system while the indicants of general antioxidant activity remain normal. This suggests the importance of the analyzed markers in PTOA pathogenesis and determined the prospects of their use for the evaluation of therapy efficacy.

Dietary Antioxidant Capacity Promotes a Protective Effect against Exacerbated Oxidative Stress in Women Undergoing Adjuvant Treatment for Breast Cancer in a Prospective Study

Breast cancer (Bca) is the most common type of cancer among women worldwide, and oxidative stress caused by adjuvant treatment may be decreased by antioxidant intake. The aim of this study is to investigate the associations between Dietary antioxidant Capacity (DaC) and oxidation and antioxidant biomarkers in women undergoing adjuvant treatment (AT) for Bca. This prospective study had a sample of 70 women (52.2 ± 10.7 y). DaC (mmol/g) was calculated using nutritional data obtained from a Food Frequency Questionnaire, and blood was collected to measure the oxidation and antioxidant biomarkers at baseline (T0), and after AT (T1). Carbonylated protein levels were inversely associated with DaC at T1 (p = 0.004); women showed an increased risk of having increment on lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and decrement on ferric reducing antioxidant power (FRAP) and reduced glutathione after AT, in response to lowered DaC (p < 0.05). Carbonylated proteins, TBARS and FRAP levels remained stable between the periods for women at the 3rd DaC tertile at T1, differentiating them from those at the 1st tertile, who showed negative changes in these biomarkers (p < 0.04). DaC may be beneficial for women undergoing AT for Bca, since it promoted a reduction in oxidative stress.

The systemic pro- and antioxidant processes in preschool children with recurrent acute respiratory diseases

Background. The imbalance of innate defense early mechanisms in children from pathogens — peroxidation and antioxidant system, can lead to a decrease in the efficiency of the entire immune system. The study of the lipid peroxidation (LPO) and antioxidant protection (AOP) status in children with recurrent acute respiratory diseases will complement the scientific data on the antimicrobial immunity formation processes. The study was aimed to increase the information value of timely detected pro- and antioxidant processes disorders in children with recurrent acute respiratory diseases by studying the primary, secondary, tertiary, and quaternary compounds of LPO and AOP in the serum. Materials and methods. Sixty children aged from 2 to 5 years were examined. Two groups were formed: group 1 — children with respiratory acute infectious more than six times per year (n = 30); group 2 — children with respiratory acute infectious six or fewer times per year (n = 30). Results. The children in group 1 more often presented with high serum levels of lipid hydroperoxides (by 80.0 %; p < 0.05), diene conjugates (by 80.0 %; p < 0.05), malonic dialdehyde (76.7 %; p < 0.05), diene ketones (76.7 %; p < 0.05), Schiff bases (76.7 %; p < 0.05). ceruloplasmin (80.0 %; p < 0.05), superoxide dismutase (80.0 %; p < 0.05), glutathione peroxidase (86.7 %; p < 0.05), catalase activity (86.7 %; p < 0.05). The values of retinol, tocopherol, ascorbic acid in children in the observation groups did not differ statistically significantly. Conclusions. The children aged from 2 to 5 years old with recurrent acute respiratory diseases have an imbalance of the LPO and AOP systems. It was characterized by a simultaneous increase in the serum content of the primary, secondary, and end-products of LPO, enzymes of anti-peroxide and anti-oxygen protection against the background of the lack of adaptive increase in the content of anti-radical compounds.

Investigation of Lipoproteins Oxidation Mechanisms by the Analysis of Lipid Hydroperoxide Isomers

The continuous formation and accumulation of oxidized lipids (e.g., lipid hydroperoxides (LOOH)) which are present even in plasma lipoproteins of healthy subjects, are ultimately considered to be linked to various diseases. Because lipid peroxidation mechanisms (i.e., radical, singlet oxygen, and enzymatic oxidation) can be suppressed by certain proper antioxidants (e.g., radical oxidation is efficiently suppressed by tocopherol), in order to suppress lipid peroxidation successfully, the determination of the peroxidation mechanism involved in the formation of LOOH is deemed crucial. In this study, to determine the peroxidation mechanisms of plasma lipoproteins of healthy subjects, we develop novel analytical methods using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine hydroperoxide (PC 16:0/18:2;OOH) and cholesteryl linoleate hydroperoxide (CE 18:2;OOH) isomers. Using the newly developed methods, these PC 16:0/18:2;OOH and CE 18:2;OOH isomers in the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of healthy subjects are analyzed. Consequently, it is found that predominant PC 16:0/18:2;OOH and CE 18:2;OOH isomers in LDL and HDL are PC 16:0/18:2;9OOH, PC 16:0/18:2;13OOH, CE 18:2;9OOH, and CE 18:2;13OOH, which means that PC and CE in LDL and HDL are mainly oxidized by radical and/or enzymatic oxidation. In conclusion, the insights about the oxidation mechanisms shown in this study would be useful for a more effective suppression of oxidative stress in the human organism.

Flight training and dietary antioxidants have mixed effects on the oxidative status of multiple tissues in a female migratory songbird

Birds, like other vertebrates, rely on a robust antioxidant system to protect themselves against oxidative imbalance caused by energy-intensive activities such as flying. Such oxidative challenges may be especially acute for females during spring migration, since they must pay the oxidative costs of flight while preparing for reproduction; however, little previous work has examined how the antioxidant system of female spring migrants responds to dietary antioxidants and the oxidative challenges of regular flying. We fed two diets to female European starlings, one supplemented with a dietary antioxidant and one without, and then flew them daily in a windtunnel for two weeks during the fall and spring migration periods. We measured the activity of enzymatic antioxidants (GPx, SOD, CAT), non-enzymatic antioxidant capacity (ORAC), and markers of oxidative damage (protein carbonyls and lipid hydroperoxides) in four tissues: pectoralis, leg, liver, and heart. Dietary antioxidants affected enzymatic antioxidant activity and lipid damage in the heart, non-enzymatic antioxidant capacity in the pectoralis, and protein damage in leg muscle. In general, birds fed less antioxidants appear to incur increased oxidative damage while upregulating non-enzymatic and enzymatic antioxidant activity, though these effects were strongly tissue-specific. We also found trends for diet x training interactions for enzymatic antioxidant activity in the heart and leg. Flight-training may condition the antioxidant system of females to dynamically respond to oxidative challenges, and females during spring migration may shift antioxidant allocation to reduce oxidative damage.

Accumulation of heavy metals and antioxidant defense system in the gametophyte of Didymodon rigidulus Hedw. in areas with high traffic loads

Background. Various modes of transport are among the main sources of environmental pollution with heavy metals and other pollutants. Bryophytes are known to accumulate heavy metals; however, metabolic changes in mosses under conditions of metal accumulation have not been extensively studied. The aim of this article was to analyze the accumulation of heavy metals, the process of lipid peroxidation (LPO) and the activity of enzymes of the antioxidant system in Didymodon rigidulus Hedw. moss collected in urban areas with an intense load created by road and railway transport. Materials and Methods. Gametophyte shoots were collected at three sampling sites in the city of Lviv (Ukraine). Site 1 was selected in a park zone, which was considered a control one; sites 2 and 3 were selected in areas with heavy road and rail traffic, respectively. Concentrations of chromium (Cr), nickel (Ni), lead (Pb), and zinc (Zn) in the moss material were determined by atomic absorption spectrophotometry. The levels of LPO products, namely lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), as well as superoxide dismutase (SOD) and catalase activities, were determined by standard methods. The results were processed using the methods of variation statistics. Results. Moss D. rigidulus growing in the park area (site 1) accumulated metals in the following order of decreasing concentration: Zn> Cr> Ni> Pb. Gametophyte shoots of D. rigidulus collected at site 2 accumulated higher levels of Pb, Zn and Ni (by 2.27, 1.78 and 1.45 times, respectively), and at site 3, higher levels of Pb and Zn (by 1.8 and 1.67 times, respectively) compared to gametophytes collected in the park zone. In the moss samples from these sites, no significant differences in the Cr content were found as compared to the control. Concentration of lipid hydroperoxides in the moss sampled at sites 2 and 3 was 4.26 and 3.75 times higher, respectively, compared to the control, and TBARS production was more intense in plant material from site 2 than from the control site. SOD and catalase activities were considerably increased in D. rigidulus moss from site 2 compared with those from the control area; however, the activity of both enzymes in the moss samples from site 3 did not significantly exceed the control levels. Conclusions. Both road and rail traffic loads contribute to the accumulation of heavy metals, especially Zn and Pb, in D. rigidulus moss growing in the surrounding areas. Under such conditions, LPO process is stimulated, which is more pronounced in moss growing in area with heavy road traffic. The increased activity of antioxidant enzymes (SOD and catalase) in moss growing in this area can play an important role in protecting bryophyte cells against metal-induced oxidative stress under conditions of intense metal accumulation.