Drug-Induced Oxidative Stress and Toxicity

Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity. [1]


Environmentally induced oxidative stress in aquatic animals

Reactive oxygen species (ROS) are an unenviable part of aerobic life. Their steady-state concentration is a balance between production and elimination providing certain steady-state ROS level. The dynamic equilibrium can be disturbed leading to enhanced ROS level and damage to cellular constituents which is called “oxidative stress”. This review describes the general processes responsible for ROS generation in aquatic animals and critically analyses used markers for identification of oxidative stress. Changes in temperature, oxygen levels and salinity can cause the stress in natural and artificial conditions via induction of disbalance between ROS production and elimination. Human borne pollutants can also enhance ROS level in hydrobionts. The role of transition metal ions, such as copper, chromium, mercury and arsenic, and pesticides, namely insecticides, herbicides, and fungicides along with oil products in induction of oxidative stress is highlighted. Last years the research in biology of free radicals was refocused from only descriptive works to molecular mechanisms with particular interest to ones enhancing tolerance. The function of some transcription regulators (Keap1–Nrf2 and HIF-1α) in coordination of organisms’ response to oxidative stress is discussed. The future directions in the field are related with more accurate description of oxidative stress, the identification of its general characteristics and mechanisms responsible for adaptation to the stress have been also discussed. The last part marks some perspectives in the study of oxidative stress in hydrobionts, which, in addition to classic use, became more and more popular to address general biological questions such as development, aging and pathologies. [2]



Hyperglycemia-induced oxidative stress in diabetic complications

Reactive oxygen species are increased by hyperglycemia. Hyperglycemia, which occurs during diabetes (both type 1 and type 2) and, to a lesser extent, during insulin resistance, causes oxidative stress. Free fatty acids, which may be elevated during inadequate glycemic control, may also be contributory. In this review, we will discuss the role of oxidative stress in diabetic complications. Oxidative stress may be important in diabetes, not just because of its role in the development of complications, but because persistent hyperglycemia, secondary to insulin resistance, may induce oxidative stress and contribute to beta cell destruction in type 2 diabetes. The focus of this review will be on the role of oxidative stress in the etiology of diabetic complications. [3]


Oxidative Stress Markers in Children with Autism Spectrum Disorders

Aims: The etiology of autism spectrum disorders (ASD) remains elusive, but oxidative stress has been suggested to play a pathological role. The understanding of the potential role of oxidative stress in the etiopathogenesis of autism would be very useful for earlier clinical, therapeutic or preventive strategies.

Sample: To evaluate the redox status, we quantified the activity of the antioxidant enzyme catalase (CAT), glutathione concentration (GSH) and markers of damage to biomolecules, malonyldialdehyde (MDA) and 8–hydroxy-2deoxyguanosine (8OHdG) in peripheral blood samples.

Place and Duration of Study: Sample: Department of Neuropediatrics and Technology Science Division. International Center for Neurological Restoration (CIREN), Havana, Cuba. May 2011- June 2012.

Methodology: We included 45 children with autism (36 males and 9 females, age-range from 3 to 11 years). 42 children of the same age were selected as a control group. The diagnosis of autism was made based on the criteria of autistic disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) (American Psychiatric Association, 1994).

Results: The total GSH content in autistic patients was significantly lower compared with the control group (0.24 ± 0.162 vs. 0.94 ± 0.115, respectively, p ≤ 0.001). Higher serum CAT, MDA and 8OHdG levels were found in children with autism compared with controls (CAT, 2.836 ± 0.479 vs. 0.689 ± 0.157, p ≤ 0.001; MDA 8.6 ± 0.5 vs. 1.76 ± 0.33 p ≤ 0.001, and 8OHdG 13.134 ± 1.33 vs.1.46 ± 0.326, p ≤ 0.001).

Conclusion: The present study supports the notion that oxidative stress is associated with autism, but additional researches are needed to investigate how it may contribute to autistic pathophysiology and these studies are currently in progress. [4]


Oxidative Stress Markers in Exotic Breeds of Rabbit during Peak of Heat Stress in Ibadan, Nigeria

The study assesses oxidative stress markers in exotic rabbit bucks at peak of heat stress in Ibadan, Nigeria. Four rabbit breeds were considered; Fauve De Bourgogne, Chinchilla, British Spot and New Zealand White. Adult rabbits (10-12 months old) were randomly selected per breed and randomly allotted to experimental units at highest temperature-humidity index. Blood samples were collected through the ear vein and assessed for serum biochemicals and oxidative stress markers; malondialdehyde, total antioxidant activity, glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase at 7 weeks of exposure to peak of thermal discomfort. The results obtained indicate that serum glucose, sodium and potassium were significantly affected by breed. Serum lipid peroxidation was also significantly lower in British Spot rabbits and highest in Fauve De Bourgogne. Serum SOD of British Spot rabbits (1.47 U/min/mg protein) was significantly highest compared with New Zealand White (1.20U/min/mg protein), Chinchilla (0.92 U/min/mg protein) and Fauve De Bourgogne (0.88 U/min/mg protein). British Spot had significantly highest serum catalase (130.73 nm H2O2 / min/mg protein) activities and an apparently highest total antioxidant activity (0.99mmol/litre) and GPx (40.32 µgGSH/min/mg protein). This suggests that British Spot breed of rabbit had better oxidative stability among the breeds of rabbits assessed.[5]
Reference

[1] Deavall, D.G., Martin, E.A., Horner, J.M. and Roberts, R., 2012. Drug-induced oxidative stress and toxicity. Journal of toxicology, 2012.

[2] Lushchak, V.I., 2011. Environmentally induced oxidative stress in aquatic animals. Aquatic toxicology, 101(1), pp.13-30.

[3] King, G.L. and Loeken, M.R., 2004. Hyperglycemia-induced oxidative stress in diabetic complications. Histochemistry and cell biology, 122(4), pp.333-338.

[4] González-Fraguela, M.E., Hung, M.L.D., Vera, H., Maragoto, C., Noris, E., Blanco, L., Galvizu, R. and Robinson, M., 2013. Oxidative stress markers in children with autism spectrum disorders. Journal of Advances in Medicine and Medical Research, pp.307-317.

[5] Jimoh, O.A., Ewuola, E.O. and Balogun, A.S., 2017. Oxidative stress markers in exotic breeds of rabbit during peak of heat stress in Ibadan, Nigeria. Journal of Advances in Biology & Biotechnology, pp.1-9.