Cadmium (Cd) is a toxic non-essential transition metal that poses a health risk for both humans and animals. It is naturally occurring in the environment as a pollutant that is derived from agricultural and industrial sources. Exposure to cadmium primarily occurs through the ingestion of contaminated food and water and, to a significant extent, through inhalation and cigarette smoking. Cadmium accumulates in plants and animals with a long half-life of about 25–30 years. Epidemiological data suggest that occupational and environmental cadmium exposure may be related to various types of cancer, including breast, lung, prostate, nasopharynx, pancreas, and kidney cancers. It has been also demonstrated that environmental cadmium may be a risk factor for osteoporosis. The liver and kidneys are extremely sensitive to cadmium’s toxic effects. This may be due to the ability of these tissues to synthesize metallothioneins (MT), which are Cd-inducible proteins that protect the cell by tightly binding the toxic cadmium ions. The oxidative stress induced by this xenobiotic may be one of the mechanisms responsible for several liver and kidney diseases. Mitochondria damage is highly plausible given that these organelles play a crucial role in the formation of ROS (reactive oxygen species) and are known to be among the key intracellular targets for cadmium. When mitochondria become dysfunctional after exposure to Cd, they produce less energy (ATP) and more ROS. Recent studies show that cadmium induces various epigenetic changes in mammalian cells, both in vivo and in vitro, causing pathogenic risks and the development of various types of cancers. The epigenetics present themselves as chemical modifications of DNA and histones that alter the chromatin without changing the sequence of the DNA nucleotide. DNA methyltransferase, histone acetyltransferase, histone deacetylase and histone methyltransferase, and micro RNA are involved in the epigenetic changes. Recently, investigations of the capability of sunflower (Helianthus annuus L.), Indian mustard (Brassica juncea), and river red gum (Eucalyptus camaldulensis) to remove cadmium from polluted soil and water have been carried out. Moreover, nanoparticles of TiO2 and Al2O3 have been used to efficiently remove cadmium from wastewater and soil. Finally, microbial fermentation has been studied as a promising method for removing cadmium from food. This review provides an update on the effects of Cd exposure on human health, focusing on the cellular and molecular alterations involved.

https://www.mdpi.com/1660-4601/17/11/3782/pdf

The Effects of Cadmium Toxicity

Cadmium is a heavy metal of considerable toxicity with destructive impact on most organ systems. It is widely distributed in humans, the chief sources of contamination being cigarette smoke, welding, and contaminated food and beverages. Toxic impacts are discussed and appear to be proportional to body burden of cadmium. Detoxification of cadmium with EDTA and other chelators is possible and has been shown to be therapeutically beneficial in humans and animals when done using established protocols.

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Cadmium Toxicity and Treatment

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs.

https://www.mdpi.com/1422-0067/14/12/24438/pdf

Oxidative Stress and Neurodegenerative Disorders

Antioxidants: Characterization, natural sources, extraction and analysis

Although the mysteries of its history and origin remain unsolved, worldwide cultivation and high-demand production for citrus fruit (genus Citrus in family Rutaceae) make it stand high among fruit crops. Growth of the citrus industry, including rapid development of the processing technology of frozen concentrated orange juice after World War II, has greatly expanded with international trade and steadily increased consumption of citrus fruits and their products during the past several decades. Characterized by the distinct aroma and delicious taste, citrus fruits have been recognized as an important food and integrated as part of our daily diet, playing key roles in supplying energy and nutrients and in health promotion. With low protein and very little fat content, citrus fruits supply mainly carbohydrates, such as sucrose, glucose, and fructose. Fresh citrus fruits are also a good source of dietary fiber, which is associated with gastrointestinal disease prevention and lowered circulating cholesterol. In addition to vitamin C, which is the most abundant nutrient, the fruits are a source of B vitamins (thiamin, pyridoxine, niacin, riboflavin, pantothenic acid, and folate), and contribute phytochemicals such as carotenoids, flavonoids, and limonoids. These biological constituents are of vital importance in human health improvement due to their antioxidant properties, ability to be converted to vitamin A (for example, β-cryptoxanthin), and purported protection from various chronic diseases.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1541-4337.2012.00201.x

History, global distribution, and nutritional importance of citrus fruits

Background: Cadmium is a potent neurotoxic heavy metal, which induces oxidative stress and membrane disturbances in brain. Melatonin is an effective antioxidant and free radical scavenger against oxidative stress. The present study was designed to investigate the neuroprotective efficacy of melatonin in pro- tecting the Cd induced changes in the activity of acetylcholinesterase (AChE), levels of lipid per- oxidation, protein carbonyls, non-enzymatic an- tioxidant, enzymatic antioxidant status, mem- brane bound ATPases and histopathology in the brain of rats. Materials and Methods: Twenty four male albino rats were used. Cadmium induced oxida- tive neurotoxicity was induced by oral adminis- tration of Cd for four weeks. Melatonin was pre- treated along with Cd for four weeks to assess its neuroprotective activity against Cd intoxica- tion. Rats treated with vehicles alone were used as controls. Results: Rats intoxicated with cadmium (5 mg/kg/day) for 4 weeks significantly (p<0.05) reduced the AChE levels in the plasma and brain, elevated the levels of thiobarbituric acid reactive substances (TBARS), lipid hydroper- oxides and protein carbonyls along with the significant (p<0.05) decrease in the levels of non-enzymatic antioxidants (GSH, TSH and vit- amins C and E), enzymatic antioxidants super- oxide dismutase (SOD), catalase (CAT), glu- tathione peroxidase (GPx), glutathione S-trans- ferase (GST) and membrane bound ATPases in the brain tissue. Administration of melatonin (10 mg/kg/day) for 4 weeks in cadmium intoxi- cated rats significantly (p<0.05) diminished the levels of oxidative stress markers, lipid peroxi- dation and protein carbonyls in brain and sig- nificantly (p<0.05) elevated the levels of non- enzymatic and enzymatic antioxidants, brain and the activities of AChE, enzymatic antioxi- dants and ATPases in brain. The histopatho- logical studies in the brain of rats also sup- ported that melatonin markedly reduced the Cd induced pathological changes and preserved the normal histological architecture of the brain tissue. Conclusions: The results of the present study suggest that melatonin may be beneficial in combating the cadmium induced oxidative neu- rotoxicity in the brain of rats.

/pdf/melatonin-abrogates-cadmium-induced-oxidative-stress-related-1ry7gfsek8.pdf

Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats.

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats.

https://cyberleninka.org/article/n/1139587.pdf

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

BACKGROUND: Cadmium is one of the potent cardiotoxic heavy metals in the en - vironment, which induces oxidative stress, dys - lipidemia and membrane disturbances in heart. Quercetin is an effective antioxidant and free radical scavenger against oxidative stress. This study was designed to evaluate the protective effect of quercetin (QE) on cardiac marker en - zymes, lipid peroxidation products, lipid profile, membrane bound ATPases and antioxidant sta - tus in cadmium (Cd)-intoxicated rats. MATERIALS AND METHODS: Twenty four male albino rats were used. Cadmium induced oxidative cardiotoxicity was induced by the oral administra - tion of Cd for four weeks. Quercetin was pretreat - ed along with Cd for four weeks to assess its car - dioprotective effect against Cd intoxication. Rats treated with vehicles alone were used as controls. RESULTS: Rats intoxicated with cadmium (5 mg/kg/day) for 4 weeks in combination with quercetin (50 mg/kg/day) respectively. Cd-in - duced cardiotoxicity and dyslipidemia was indi - cated by increased activities of marker enzymes such as creatine kinase-MB, aspartate transami - nase, alanine transaminase, alkaline phos - phatase and lactate dehydrogenase in serum. In addition, the levels of lipid peroxidation products and protein carbonyl contents in heart were sig - nificantly ( p < 0.05) increased and the activities of enzymic antioxidants such as superoxide dis - mutase, catalase, glutathione peroxidase, glu - tathione reductase and glutathione-S-transferase in the heart and non-enzymic antioxidants such as glutathione, vitamin C and E in the heart were significantly ( p < 0.05) decreased in Cd intoxicat - ed rats. The levels total cholesterol (TC), triglyc - erides (TG), phospholipidis (PL), free fatty acids (FFA), LDL andVLDL were significantly ( p < 0.05) increased and the level of HDL was significantly decreased in the serum of Cd-treated rats. Cd in - toxication also increased the levels ofTC,TG and FFA and decreased the level of PL in the heart tissue. Further Cd treatment significantly ( p < 0.05) decreased the levels of membrane bound ATP ases in heart. QE treatment along with Cd showed significant protective effect on all the biochemical parameters studied. Histopathologi - cal findings of QE and Cd treated heart con -

/pdf/quercetin-potentially-attenuates-cadmium-induced-oxidative-18mv0d2pxy.pdf

Quercetin potentially attenuates cadmium induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats.

Cadmium (Cd) exposure results in numerous pathological consequences including oxidative stress and dyslipidemia. The present study was designed to investigate the efficacy of combined treatment with quercetin (QE) and α-tocopherol (AT) against Cd-induced oxidative stress and alterations in lipids and lipoproteins in the plasma and liver of rats. Oral administration of Cd (5 mg/kg bw/d) for 4 wk has shown a significant (P 0.05) reduction in the levels of reduced glutathione (GSH), high density lipoprotein cholesterol (HDL-C), and the activity of lecithin cholesterol acyl transferase (LCAT) in plasma. In addition, the levels of hepatic thiobarbituric acid reactive substances (TBARS), LOOH, conjugated dienes (CD), protein carbonyls (PC), and the activity of HMG-CoA reductase, levels of cholesterol, FFA, and TGs were significantly (P > 0.05) increased and the level of PL is significantly (P > 0.05) decreased along with the decreased activity of LCAT in the liver of Cd-treated rats. Oral supplementation with QE (50 mg/kg bw/d) and AT (50 mg/kg bw/d) for 4 wk in Cd intoxicated rats significantly (P > 0.05) has reduced the plasma levels of TBARS, LOOH, GSH, cholesterol, FFA, TGs, VLDL-C, LDL-C, and the activity of HMG-CoA and significantly (P > 0.05) has increased the activity of LCAT and the plasma levels of HDL-C. The oral supplementation also significantly (P > 0.05) has reduced the hepatic oxidative stress markers, cholesterol, TGs, FFA, and significantly (P > 0.05) has increased the LCAT activity and the PL in liver. Our results indicate that the combined treatment with QE and AT has normalized all the previously mentioned biochemical parameters in Cd-intoxicated rats than the individual treatments. The combined treatment has provided remarkable protection against Cd-induced oxidative stress and alterations in lipid metabolism and, thereby, reduced the Cd-mediated cardiovascular diseases.

Amelioration of cadmium-induced oxidative stress, impairment in lipids and plasma lipoproteins by the combined treatment with quercetin and α-tocopherol in rats.

K. Shagirtha

Papers

Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats.

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats.

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

Quercetin potentially attenuates cadmium induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats.

Amelioration of cadmium-induced oxidative stress, impairment in lipids and plasma lipoproteins by the combined treatment with quercetin and α-tocopherol in rats.